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Thorens, Louison, Knut Jørgen Måløy, Mickaël Bourgoin, and Stéphane Santucci. "Taming the Janssen effect." EPJ Web of Conferences 249 (2021): 08004. http://dx.doi.org/10.1051/epjconf/202124908004.
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We investigate both experimentally and theoretically the apparent mass of a ferromagnetic granular assembly filling a cylindrical container and submitted to a magnetic field B, aligned vertically along the silo. We show that the mass of the ferromagnetic granular column depends strongly on the applied magnetic field. Notably, our measurements deviate strongly from the exponential saturation of the measured mass as a function of the true mass of the grain packing, as predicted by Janssen [H.A. Janssen, Vereins Eutscher Ingenieure Zeitschrift, 1045 (1895)]. In particular, the measured mass of tall columns decreases systematically as the amplitude of the magnetic field increases. We rationalize our experimental findings by considering the induced magnetic dipole-dipole interactions within the whole packing. We show the emergence of a global magnetic radial force along the walls of the silos, fully determined by the external magnetic field. The resulting tunable frictional interactions allows a full control of the effective mass of the ferromagnetic granular column.
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Maksuwan, Atirat. "Janssen’s Effect in Mechanical Behavior and Fracture of Granular Materials." Materials Science Forum 883 (January 2017): 7–11. http://dx.doi.org/10.4028/www.scientific.net/msf.883.7.
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In 1985, H.A. Janssen studied the structure of the forces inside a silo filled with granular materials, so-called Janssen’s Effect Method (J.E.M). This method is a unique property of confined granular materials. The pressure at the bottom saturated with an increasing filling height due to internal friction with side walls. In this research, we focus on the study of granular cohesionless materials such as sands and gravels, these forces are explained by adsorption and capillary phenomenon. Our main result shows that positive water pressures generate a mechanical effect with tendencies of removing the components of the porous medium corresponding to the mechanical buoyancy force (FB) that increases with increasing θ from calculated by Janssen's effect method. The topic in this research is once importance in study physical processes of the problem in the Geology Physics (i.e. the factor causing landslide).
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Nurmohamed, M. T., I. Van der Horst-Bruinsma, A. W. Van Kuijk, S. Siebert, P. Bergmans, K. De Vlam, E. Gremese, et al. "SAT0432 EFFECT OF SEX ON DISEASE CHARACTERISTICS AND DISEASE IMPACT IN PATIENTS WITH PSORIATIC ARTHRITIS (PsA): INSIGHTS FROM THE REAL-WORLD, OBSERVATIONAL MULTINATIONAL PsABio COHORT." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1171.1–1173. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2771.
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Background:Female sex has been associated with more severe disease and poorer treatment outcomes in PsA. These observations are often based on small populations or national cohorts/registries.Objectives:To investigate the effects of sex on disease characteristics and disease impact in PsA, using data of 929 consecutive patients (pts) from PsABio.Methods:PsABio is a real-world, non-interventional European study in PsA pts treated with UST or TNFi based on their rheumatologist’s choice. Observed male and female baseline (BL) data were described and compared using 95% CI.Results:Women in PsABio (n=512 [55%]) were numerically older than men (mean [SD]: 50.5 [12.7] / 48.7 [12.3] years, respectively). Women were more obese (BMI >30), % (95% CI): F: 35 (30, 39), M: 24 (20, 29), men more overweight (BMI >25–30): F: 31 (27, 36), M:51 (46, 57). Age at diagnosis, delay from first symptom to diagnosis, and disease duration were similar for both sexes.Women entered PsABio more often on 3rd line treatment, whereas men started on 1st-line biologic treatment more often (F/M 1st line 47%/55%; 2nd line 34%/33%; 3rd line 20%/12%). Numerically, concomitant MTX was given more often to women vs men (32% vs 27%). At BL, 60% of women and 64% of men were on NSAIDs; 7.9% and 2.5% on antidepressant drugs. Women had significantly more comorbidities, with numerically more cardiovascular disease and anxiety/depression, and 3 times more IBD.Women had significantly higher 68 tender joint counts (TJC): 13.0 vs 10.4, while 66 swollen joint counts were not significantly different: 5.8 vs 5.5. Axial or combined axial-peripheral disease was similarly frequent, in 29% of women and 26% of men (Figs. 1, 2).Clinical Disease Activity index for PSoriatic Arthritis (cDAPSA) was higher in women (31.8 vs 27.3); pt-reported levels of pain, global disease activity (VAS scales) and higher TJC contributed to this. While enthesitis prevalence (based on Leeds Enthesitis Index) was comparable, men had significantly more frequent dactylitis, nail disease and worse skin psoriasis. At BL, 3.4% of women vs 7.1% of men, were in MDA.Regarding physical functioning (HAQ-DI), impact of disease (PSAID-12) and quality of life (EQ5D-3L health state), women with PsA starting a biologic (b)DMARD, expressed significantly greater negative impact and more limitations due to their disease (Fig. 2).Conclusion:In routine care, women with PsA starting a bDMARD presented with worse outcomes over a range of assessments compared with men (higher pt-reported pain and disease activity, TJC, and worse physical functioning and QoL), while men had worse dactylitis and psoriasis. Follow-up analysis will report whether the effects of biologic therapy are different in both sexes. The increased prevalence of associated features related to pain and impact on functioning and QoL may indicate the need for a more comprehensive treatment approach for women to avoid unnecessary and premature bDMARD stop or switch.Acknowledgments:This study was funded by Janssen.Disclosure of Interests:Michael T Nurmohamed Grant/research support from: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Consultant of: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Speakers bureau: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Irene van der Horst-Bruinsma Grant/research support from: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Consultant of: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Arno WR van Kuijk Grant/research support from: Janssen, Stefan Siebert Grant/research support from: BMS, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Boehringer Ingelheim, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Celgene, Janssen, Novartis, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Kurt de Vlam Consultant of: Celgene Corporation, Eli Lilly, Novartis, Pfizer, UCB – consultant, Speakers bureau: Celgene Corporation, Eli Lilly, Novartis, Pfizer, UCB – speakers bureau and honoraria, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Beatriz Joven-Ibáñez Speakers bureau: Abbvie, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Tatiana Korotaeva Grant/research support from: Pfizer, Consultant of: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Speakers bureau: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Wim Noel Employee of: Janssen Pharmaceuticals NV, Petros Sfikakis Grant/research support from: Grant/research support from Abvie, Novartis, MSD, Actelion, Amgen, Pfizer, Janssen Pharmaceutical, UCB, Elke Theander Employee of: Janssen-Cilag Sweden AB, Josef S. Smolen Grant/research support from: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB
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Saint-Michel, Brice, Marc Georgelin, Sylvain Deville, and Alain Pocheau. "Wall friction and Janssen effect in the solidification of suspensions." Soft Matter 14, no. 46 (2018): 9498–510. http://dx.doi.org/10.1039/c8sm01572d.
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Helliwell, P., P. Rahman, A. Deodhar, A. Kollmeier, E. C. Hsia, B. Zhou, X. Lin, C. Han, and P. J. Mease. "SAT0421 GUSELKUMAB DEMONSTRATED AN INDEPENDENT TREATMENT EFFECT ON FATIGUE AFTER ADJUSTMENT FOR CLINICAL RESPONSE (ACR20) IN PATIENTS WITH PSORIATIC ARTHRITIS: RESULTS FROM PHASE-3 TRIALS DISCOVER 1 & 2." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1164.2–1164. http://dx.doi.org/10.1136/annrheumdis-2020-eular.401.
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Background:DISCOVER 1 and 2 are phase-3 trials of guselkumab (GUS, a monoclonal antibody that specifically binds the p19-subunit of IL-23) in patients with psoriatic arthritis (PsA). In both trials, treatment with GUS led to significantly more improvement than placebo (PBO) in the primary endpoint (ACR20) as well as in other measures of arthritis and psoriasis at week (W) 24.1,2Objectives:To evaluate the effect of GUS on fatigue in DISC 1 & 2 using the patient reported outcome (PRO) FACIT-Fatigue, which has demonstrated content validity and strong psychometric properties in clinical trials.3Methods:DISC 1 & 2 enrolled patients with active PsA, despite nonbiologic DMARDS and/or NSAIDS, who were mostly biologic naïve except for ~30% of patients in DISC 1 who had received 1-2 TNFi. Patients were randomized (1:1:1) in a blinded fashion to subcutaneous GUS 100 mg at W0 and W4 then every (q) 8W, to GUS 100 mg q4W, or to matching PBO. Concomitant treatment with select non-biologic DMARDS, oral corticosteroids, and NSAIDs was allowed. The FACIT-Fatigue is a 13-item PRO instrument assessing fatigue and its impact on daily activities and function over the past seven days, with a total score ranging from 0 to 52, higher score denoting less fatigue. A change of ≥4 points is identified as clinically meaningful.3Change from baseline in FACIT-Fatigue was analyzed using MMRM (Figure). Independence of treatment effect on FACIT-Fatigue from effect on ACR20 was assessed using Mediation Analysis4(Table) to estimate the natural direct effect (NDE) and natural indirect effect (NIE) mediated by ACR20 response.Results:At baseline in DISC 1 & 2, the mean FACIT-fatigue scores (SD) were 30.4 (10.4) and 29.7 (9.7), respectively, indicating moderate to severe fatigue. In both DISCOVER 1 & 2 trials, treatment with GUS led to improvements in FACIT-Fatigue scores compared with PBO as early as W8 (Figure). 54%-63% of GUS patients compared with 35%-46% of PBO patients achieved clinically meaningful improvement (≥4 points) in FACIT-Fatigue (P≤0.003). Mediation analysis revealed that the independent treatment effects on fatigue after adjustment for ACR20 response (Natural Direct Effect [NDE], Table) were 12-36% in the q8W GUS dosing group and 69% -70% in the q4W GUS group.Conclusion:In 2 phase-3 trials, treatment with GUS of patients with active PsA led to significant improvements compared to PBO in fatigue, including substantial effects on FACIT-Fatigue that were independent of the effects on ACR 20, especially for the q4W dosing group.References:[1]Deodhar et al. ACR 2019. Abstract #807. Arthr Rheumatol. 2019;71 S10: 1386[2]Mease et al. ACR 2019. Abstract # L13. Arthr Rheumatol. 2019;71 S10:5247[3]Cella et al. Journal of Patient-Reported Outcomes. 2019;3:30[4]Valeri et al. Psychologic Meth. 2013;18:137Table.Mediation Analysis of the Effect of ACR 20 Response on Change from Baseline in FACIT-Fatigue Score at Week 24EffectGUS 100 mg q8W vs. PBOEstimate (95% CI)GUS 100 mg q4W vs. PBOEstimate (95% CI)DISCOVER 1NDE0.36 (-1.7, 2.4)2.60 (0.6, 4.5)*NIE2.75 (1.4, 4.3)*1.20 (0.3, 2.3)*Total Effect3.12 (1.0, 5.2)*3.79 (1.9, 5.4)*Proportion Independent11.7%68.5%Proportion Mediated88.3%31.5%DISCOVER 2NDE1.44 (-0.1, 3.0)2.49 (1.0, 4.1)*NIE2.53 (1.6, 3.6)*1.09 (0.4, 1.9)*Total Effect3.97 (2.4, 5.5)*3.58 (2.1, 5.0)*Proportion Independent36.3%69.7%Proportion Mediated63.7%30.3%*P vs placebo<0.02NDE=Natural Direct Effect (effect on FACIT-F beyond effect on ACR20), NIE=Natural Indirect Effect (effect on FACIT-F mediated by ACR20)Mediation analysis4used linear and logistics regression models with Bootstrapping methodAcknowledgments:NoneDisclosure of Interests:Philip Helliwell: None declared, Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Bei Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xiwu Lin Employee of: Janssen Research & Development, LLC, Chenglong Han Employee of: Janssen Research & Development, LLC, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau
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Mease, P. J., X. Baraliakos, V. Chandran, E. Soriano, P. Nash, A. Deodhar, E. Rampakakis, et al. "AB1108 EFFECT OF GUSELKUMAB ADMINISTERED EVERY 8 WEEKS IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS PERSISTS BETWEEN CONSECUTIVE DOSES AND IS DURABLE: POST HOC ANALYSIS OF A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1782–83. http://dx.doi.org/10.1136/annrheumdis-2023-eular.642.
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BackgroundThe efficacy of guselkumab (GUS), a fully human IL-23p19 subunit inhibitor, in patients (pts) with active psoriatic arthritis (PsA) has been previously shown across a variety of PsA domains and baseline (BL) pt characteristics[1-3]. Given the central role of the IL-23/Th17 pathway in PsA, it has been hypothesized that IL-23 inhibition with GUS may provide persistent and durable clinical responses between doses and over time when administered every 8 weeks (Q8W).ObjectivesTo assess at the pt level the persistence of effect of GUS Q8W between doses and its durability of effect over time.MethodsDISCOVER-2 was a phase 3, randomized, double-blind, placebo (PBO)-controlled study that enrolled pts with active PsA despite standard therapies. Pts were biologic-naïve, had tender and swollen joint counts (TJC/SJC) each ≥5, and C-reactive protein (CRP) ≥0.6 mg/dL. Pts were randomized 1:1:1 to GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or PBO with crossover to GUS 100 mg Q4W at W24. In the current analysis, only pts treated with GUS Q8W (N=248) were included. Persistence of effect between consecutive dosing visits was described with the proportion of pts maintaining response (as defined below) in outcomes assessed during dosing visits (Disease Activity index for PsA [DAPSA], clinical DAPSA [cDAPSA]). Durability of effect was assessed with the Kaplan Meier estimator of the survival function where each pt contributed follow-up from the first time of achievement of clinical response within the 24-week period and the time of loss of response or last available assessment through W100. Definitions of clinical response included achievement of clear/almost clear skin (investigator’s global assessment [IGA] 0/1; among pts with BL IGA>1) or minimal clinically important improvements (MCII) in DAPSA (≥7.25), cDAPSA (≥5.7), skin visual analog scale (VAS; ≥15 mm), and PsA Disease Activity Score (PASDAS; ≥0.8).ResultsBetween consecutive (Q8W) dosing visits through W52, the proportion of pts maintaining response ranged from 93.3% (DAPSA MCII between W4 and W12) to 99.1% (DAPSA/cDAPSA MCII between W28 and W36), depending on the time interval. Among pts showing clinical response within the first 24 weeks, the estimated mean (SE) duration of maintenance was 58.6 (2.2) weeks for DAPSA MCII, 52.4 (2.0) weeks for cDAPSA MCII, 75.7 (1.6) weeks for.IGA 0/1, 71.7 (1.9) weeks for skin VAS MCII, and 76.7 (1.4) weeks for PASDAS MCII (Figure 1). As estimated probabilities of maintenance of effect at W100 were between 65% (IGA 0/1) and 90% (PASDAS MCII) for all outcomes assessed, median duration of effect could not be calculated.ConclusionTreatment with GUS Q8W was associated with long-lasting effects in both joint- and skin-related outcomes, as well as in multi-domain composite outcomes, in individuals with PsA. These results highlight that, in addition to continuous improvement in clinical response rates over time, GUS Q8W provides consistent and highly durable responses between consecutive doses.References[1]McInnes IB, et al.Arthritis Rheumatol. 2022;74:475.[2]Ritchlin CT, et al.RMD Open. 2022;8:e002195.[3]Ritchlin CT, et al.Arthritis Rheumatol. 2022;74 (suppl 9).Acknowledgements:NIL.Disclosure of InterestsPhilip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Xenofon Baraliakos Speakers bureau: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Vinod Chandran Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, and Eli Lilly, Enrique Soriano Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Janssen, Novartis, and Roche, Grant/research support from: AbbVie, Janssen, Novartis, Pfizer, Roche, and UCB, Peter Nash Speakers bureau: UCB, AbbVie, Pfizer, Eli Lilly, Novartis, GlaxoSmithKline, MSD, Samsung, Janssen, Gilead/Galapagos, Boehringer-Ingelheim, Sun, Consultant of: UCB, AbbVie, Pfizer, Eli Lilly, Novartis, GlaxoSmithKline, MSD, Samsung, Janssen, Gilead/Galapagos, Boehringer-Ingelheim, Sun, Grant/research support from: UCB, AbbVie, Pfizer, Eli Lilly, Novartis, GlaxoSmithKline, MSD, Samsung, Janssen, Gilead/Galapagos, Boehringer-Ingelheim, Sun, Atul Deodhar Speakers bureau: Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, and UCB, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, Inc., Natalie Shiff Shareholder of: AbbVie, Gilead, Iovance, Jazz Pharmaceuticals, Johnson & Johnson, Novavax, and Viatris, Employee of: Janssen Scientific Affairs, LLC, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies, Joseph F. Merola Consultant of: Amgen, Bristol Myers Squibb, AbbVie, Dermavant, Eli Lilly, Incyte, Novartis, Janssen, UCB, Sanofi-Regeneron, Sun Pharma, Biogen, Pfizer and Leo Pharma, Iain McInnes Shareholder of: Causeway Therapeutics, and Evelo Compugen, Consultant of: AstraZeneca, AbbVie, Bristol Myers Squibb, Amgen, Eli Lilly, Cabaletta, Compugen, GlaxoSmithKline, Gilead, Janssen, Novartis, Pfizer, Sanofi, Roche, and UCB, Grant/research support from: AstraZeneca, Bristol Myers Squibb, Amgen, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Roche, and UCB.
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Gossec, L., S. Siebert, P. Bergmans, K. De Vlam, E. Gremese, B. Joven-Ibáñez, T. Korotaeva, et al. "SAT0398 PERSISTENCE OF USTEKINUMAB (UST) OR TNF INHIBITOR (TNFI) TREATMENT IN PSORIATIC ARTHRITIS (PsA): INSIGHTS FROM THE LARGE, PROSPECTIVE, MULTINATIONAL, REAL-WORLD PsABio COHORT." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1149–50. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2127.
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Background:Several biologic DMARDs (bDMARDs) exist for PsA, TNFi and UST being the earliest on European markets. When bDMARDs are insufficiently effective, later-line bDMARDs typically have shorter persistence. Treatment persistence reflects a mix of effectiveness and adverse events (AEs), and persistence data are limited in PsA.Objectives:Comparative analysis of 1-year persistence of UST and TNFi within the prospective PsABio cohort.Methods:PsABio is an observational, multinational study of PsA patients (pts) treated with 1st to 3rd line UST or TNFi at their rheumatologist’s discretion.1Treatment persistence (up to 15 months of follow-up) was defined as time between start of first bDMARD treatment in PsABio, and either stop or switch to another bDMARD, or withdrawal.Persistence of UST and TNFi is shown by Kaplan-Meier curves and compared using Cox regression analysis, with propensity score (PS) to adjust for baseline imbalanced demographic and disease-related covariates (age, sex, bDMARD line, BMI, Clinical Disease Activity index for PSoriatic Arthritis [cDAPSA], 12-item PsA Impact of Disease [PsAID-12], Fibromyalgia Rapid Screening Tool [FiRST] score, co-treatments with MTX, NSAIDs, glucocorticoids, cardiovascular/metabolic comorbidities, dactylitis, enthesitis and body surface area [BSA]). Factors including concomitant MTX use and skin involvement: <3%, 3–10% and >10%, were added to the Cox model to investigate their impact on the PS-adjusted treatment effect.Results:Of 438 and 455 pts who started UST and TNF, respectively, 121 (28%) and 134 (29%) stopped or switched treatment before Month 15, with differences (as expected) according to treatment line (Fig. 1a, b). Reasons for stop/switch were related to safety/AEs in 12% (UST) and 28% (TNFi), and effectiveness (joints, nails or skin) in 77% (UST) and 69% (TNFi) of pts.The observed mean time on drug was 397 days for UST and 385 days for TNFi pts (1st line 410/397 days, 2nd 390/382 days, 3rd 381/338 days). Fig. 1b shows similar persistence for all drugs and treatment lines, except for lower persistence in TNFi 3rd line vs 1st/2nd. In PS-adjusted Cox analysis, no statistically significant difference between UST and TNFi persistence was seen; hazard ratio (HR; 95% CI) for stop/switch bDMARD (UST vs TNFi) was 0.82 (0.60, 1.13). In the model, bDMARD monotherapy (without MTX) and extensive skin involvement (BSA >10%), showed significantly better persistence for UST (HR 0.61 [0.42, 0.90] and 0.41 [0.19, 0.89] respectively; unadjusted Kaplan-Meier graphs shown in Fig. 1c, d). MTX co-therapy and low BSA did not affect the PS-adjusted treatment effect. Other factors added to the PS-adjusted Cox model did not show significant effects.Conclusion:In this real-world PsA cohort undergoing bDMARD treatment, persistence was generally comparable for UST and TNFi, but some clinical situations led to better drug persistence with UST compared to TNFi – particularly monotherapy, more extensive skin involvement, and in 3rd-line treatment. Our data emphasise the importance of skin involvement for pts with PsA.References:[1]Gossec L, et al.Ann Rheum Dis. 2018;77(suppl 2):Abstract AB0928Acknowledgments:This study was funded by Janssen.Disclosure of Interests:Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, Stefan Siebert Grant/research support from: BMS, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Boehringer Ingelheim, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Celgene, Janssen, Novartis, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Kurt de Vlam Consultant of: Celgene Corporation, Eli Lilly, Novartis, Pfizer, UCB – consultant, Speakers bureau: Celgene Corporation, Eli Lilly, Novartis, Pfizer, UCB – speakers bureau and honoraria, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Beatriz Joven-Ibáñez Speakers bureau: Abbvie, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Tatiana Korotaeva Grant/research support from: Pfizer, Consultant of: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Speakers bureau: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Wim Noel Employee of: Janssen Pharmaceuticals NV, Michael T Nurmohamed Grant/research support from: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Consultant of: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Speakers bureau: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Petros Sfikakis Grant/research support from: Grant/research support from Abvie, Novartis, MSD, Actelion, Amgen, Pfizer, Janssen Pharmaceutical, UCB, Elke Theander Employee of: Janssen-Cilag Sweden AB, Josef S. Smolen Grant/research support from: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi
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Nash, P., I. McInnes, C. T. Ritchlin, W. C. Tsai, Y. Y. Leung, L. S. Tam, D. Furtner, et al. "AB0525 GUSELKUMAB TREATMENT SHOWS RAPID ONSET OF EFFECT ON COMPONENTS OF AMERICAN COLLEGE OF RHEUMATOLOGY RESPONSE CRITERIA: RESULTS OF 2 RANDOMIZED PHASE 3 TRIALS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1290–91. http://dx.doi.org/10.1136/annrheumdis-2021-eular.434.
Full textAbstract:
Background:Guselkumab (GUS), an anti-interleukin-23p19-subunit monoclonal antibody, demonstrated efficacy vs placebo (PBO) in achieving American College of Rheumatology 20% improvement (ACR20) response in patients (pts) with active psoriatic arthritis (PsA) in two phase 3 trials, DISCOVER-1 & 2.1,2Objectives:To assess the differential treatment effects of GUS across individual components of ACR response in PsA pts participating in the DISCOVER-1 & 2 trials.Methods:In DISCOVER-1 & 2, 1120 pts were randomized & treated with GUS 100 mg every 4 weeks (Q4W; N=373); GUS 100 mg at Week (W)0 and W4, then Q8W (N=375); or matching PBO (N=372). Pts were evaluated by independent joint assessors at study visits. ACR20 response is defined as ≥20% improvement from baseline in both tender joint count (0-68 [TJC68]) and swollen joint count (0-66 [SJC66]) and ≥20% improvement from baseline in ≥3 of 5 assessments: Patient Assessment of Pain [Pt Pain], Patient Assessment of Global Disease Activity (arthritis) [PtGA], Physician Assessment of Global Disease Activity [PGA], Patient assessment of physical function as measured by Disability Index of the Health Assessment Questionnaire (HAQ-DI), and C-reactive protein (CRP). For each ACR component, achievement of ≥20% improvement from baseline was assessed over time through W24 for the combined (Q4W+Q8W) GUS groups, and median time to onset of treatment effect was determined with Kaplan-Meier curves by randomized group.Results:Median time to response for all components except SJC66 occurred earlier with GUS than PBO. Time to onset of ACR20 treatment effect is shown in Figure 1. CRP data show 56% of GUS-treated pts had diminution of systemic inflammation by W4 (Table 1). Reduction in systemic inflammation was accompanied or rapidly followed by GUS-related improvement in both PtGA and PGA (median W4-8). Although SJC66/TJC68 data showed similar patterns, there was also a high PBO response (data not shown). Consistent with early reductions in systemic inflammation, 48-61% of GUS-treated pts had ≥20% improvement in TJC68/SJC66/PGA at W4 (Table 1), and 45-48% had ≥20% improvement in HAQ-DI, PtGA, and Pt Pain by W8. By W24, >80% of GUS-treated pts had ≥20% improvement in SJC66/TJC68/PGA, followed by 63-64% with this degree of improvement in PtGA, CRP, and Pt Pain, and 57% for HAQ-DI.Conclusion:GUS demonstrated ACR20 improvements with separation from PBO in ACR components as early as W4, which is consistent with reduced inflammation by GUS and prior serological studies.3 At early study time points, both pts and physicians were able to discern improvements in signs and symptoms of arthritis that rapidly followed reductions in systemic inflammation (CRP). The predominant drivers of ACR20 response rates at W24 in GUS pts were SJC66/TJC68/PGA.References:[1]Deodhar A et al. Lancet. 2020;395:1115-25[2]Mease P et al. Lancet. 2020;395:1126-36[3]Siebert S et al. EULAR 2020. Presentation OP0229Table 1.W4W8W12W16W20W24ACR20203950566061HAQ-DI score364552545657SJC66617484868788TJC68486575798081PGA506774788181PtGA354858596264Pt Pain324855586163CRP566062636464Figure 1Disclosure of Interests:Peter Nash Consultant of: AbbVie, Bristol Myers Squibb, Boehringer, Celgene, Gilead, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Sandoz, Sun, Grant/research support from: AbbVie, Bristol Myers Squibb, Boehringer, Celgene, Gilead, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Sandoz, Sun, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Janssen, Eli Lilly, Gilead, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, and UCB, Wen-Chan Tsai Consultant of: AbbVie, Eli Lilly, Janssen, Pfizer, and Novartis, Ying Ying Leung Consultant of: Abbvie, Eli Lilly, Janssen, and Novartis, Lai-Shan Tam Consultant of: AbbVie, Boehringer Ingelheim, Janssen, Lilly, Pfizer, and Sanofi, Grant/research support from: Amgen, Boehringer Ingelheim, Janssen, GSK, Novartis, and Pfizer, Daniel Furtner Employee of: Janssen, a division of Johnson & Johnson Pte. Ltd., May Shawi Employee of: Janssen Research and Development, LLC, Stephen Xu Employee of: Janssen Research and Development LLC, Shihong Sheng Employee of: Janssen Research and Development, LLC, Alexa Kollmeier Employee of: Janssen Research and Development, LLC, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, and UCB.
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Goupille, P., F. Behrens, L. C. Coates, J. Gratacos-Masmitja, P. J. Mease, D. D. Gladman, P. Nash, et al. "POS1044 EFFECT OF SECUKINUMAB VERSUS ADALIMUMAB ON ACR CORE COMPONENTS AND HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH PSORIATIC ARTHRITIS: RESULTS FROM THE EXCEED STUDY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 797–98. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1562.
Full textAbstract:
Background:EXCEED (NCT02745080) was the first fully blinded head-to-head trial to evaluate the efficacy and safety of secukinumab (SEC) versus (vs) adalimumab (ADA) monotherapy in patients with active psoriatic arthritis (PsA) with a primary endpoint of American College of Rheumatology (ACR) 20 at Week 52. Although SEC narrowly missed statistical significance for superiority vs ADA, numerically higher response for other musculoskeletal endpoints and composite indices were observed with SEC.1Objectives:To explore the effect of SEC and ADA on ACR core components, function and Health-related Quality of Life (HRQoL) outcomes.Methods:Patients were randomised 1:1 to receive SEC 300 mg (N=426) subcutaneous (s.c.) at baseline, Week 1-4, followed by every 4 weeks until Week 48 or ADA 40 mg (N=427) s.c. at baseline followed by same dosing every 2 weeks until Week 50. The primary, key secondary and some exploratory endpoints at Week 52 were previously reported.1 A supportive analysis for ACR50 response using logistic regression model and trimmed means model for Health Assessment Questionnaire-Disability Index (HAQ-DI) with gender and smoking status as factors was performed to adjust for imbalances in baseline characteristics. An exploratory analysis of ACR core components with SEC vs ADA at Week 52 was conducted using a mixed-effects repeated measures model that included tender and swollen joint counts, patient and physician global assessment, PsA pain (VAS) and erythrocyte sedimentation rate. HRQoL variables were also exploratory and assessed based on Short Form Health Survey Physical/Mental Component Summary (SF-36 PCS/MCS) scores and Dermatology Life Quality Index (DLQI).Results:The demographic and baseline disease characteristics were comparable across treatment groups, except for an imbalance in sex (females: 51.2% vs 46.4%) and smoking status (yes: 21.8% vs 17.8%) in SEC and ADA group, respectively. At Week 52, ACR50 responses were 49.0% and 44.8% (P=0.0929) and HAQ-DI mean change from baseline were −0.69 and −0.58 (P=0.0314) in SEC and ADA treatment groups, respectively after adjusting for gender and smoking status. No major difference across ACR core components was observed in both treatment groups at Week 52 (Table 1). At Week 52, SEC presented similar improvement in SF-36 PCS/MCS score and numerically higher improvement in DLQI compared to ADA (Figure 1).Conclusion:Secukinumab provided similar improvements in ACR core components and SF-36 based quality of life at Week 52 with adalimumab. Greater improvement in HAQ-DI response and DLQI was demonstrated with secukinumab compared to adalimumab.References:[1]McInnes IB, et al. Lancet. 2020; 395:1496–505.Table 1.ACR Core Components at Week 52VariablesSecukinumab 300 mg(N=426)Adalimumab 40 mg(N=427)P-valueBL, mean ± SELSM change from BL ± SEBL, mean ± SELSM change from BL ± SETender joint score(based on 78 joints)19.4 ± 13.86−14.27 ± 0.4420.6 ± 14.81−13.90 ± 0.450.5549Swollen joint score(based on 76 joints)9.7 ± 7.30−8.41 ± 0.1910.2 ± 7.86−8.06 ± 0.200.1962Patients global assessment64.0 ± 19.67−33.81 ± 1.1461.9 ± 20.75−31.61 ± 1.190.1825Physicians global assessment60.0 ± 17.12−46.24 ± 0.8061.4 ± 15.92−43.63 ± 0.840.0243Psoriatic arthritis pain (VAS)58.6 ± 23.49−30.21 ± 1.1857.9 ± 22.42−29.44 ± 1.230.6500Erythrocyte sedimentation rate (mm/h)23.8 ± 18.93−9.63 ± 0.6223.9 ± 17.99−9.28 ± 0.640.7029LS mean and nominal P-values are from a mixed-effects repeated measures model with treatment group, analysis visit as factors, weight and BL score as covariates, and by treatment and BL score as interaction terms, unstructured covariance structure. ACR, American College of Rheumatology; BL, baseline; LSM, least squares mean; N, total number of randomised patients; SE, standard error; VAS, visual analogue scaleFigure 1.HRQoL Analysis at Week 52Disclosure of Interests:Philippe Goupille Speakers bureau: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Eli Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Eli Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Grant/research support from: AbbVie, Amgen, Biogen, BMS, Celgene, Chugai, Janssen, Eli Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Sanofi and UCB, Frank Behrens Paid instructor for: Eli Lilly, Consultant of: Pfizer, AbbVie, Sanofi, Eli Lilly, Novartis, Genzyme, Boehringer Ingelheim, Janssen, MSD, Celgene, Roche and Chugai, Grant/research support from: Pfizer, Janssen, Chugai, Celgene and Roche, Laura C Coates Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Biogen, BMS, Celgene, Domain, Eli Lilly, Gilead, GSK, Janssen, Medac, Novartis, Pfizer, Serac and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Jordi Gratacos-Masmitja Speakers bureau: AbbVie, Amgen, BMS, Celgene, Janssen, Eli Lilly, Novartis and Pfizer, Consultant of: AbbVie, Amgen, BMS, Celgene, Janssen, Eli Lilly, Novartis and Pfizer, Grant/research support from: AbbVie, Amgen, BMS, Celgene, Janssen, Eli Lilly, Novartis and Pfizer, Philip J Mease Speakers bureau: AbbVie, Amgen, Genentech, Janssen, Eli Lilly, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Galapagos, Celgene, Genentech, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Galapagos, Genentech, Gilead, Janssen, Eli Lilly, Merck, Novartis, Pfizer, SUN Pharma, and UCB, Dafna D Gladman Consultant of: Amgen, AbbVie, BMS, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer and UCB, Grant/research support from: Amgen, AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Peter Nash Speakers bureau: Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, Celgene, UCB, Eli Lilly, MSD, Sanofi, Gilead, Consultant of: Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, Celgene, UCB, Eli Lilly, MSD, Sanofi, Gilead, Grant/research support from: Novartis, Abbvie, Roche, Pfizer, BMS, Janssen, Celgene, UCB, Eli Lilly, MSD, Sanofi, Gilead, Arthur Kavanaugh Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, and UCB, Ruvie Martin Shareholder of: Novartis, Employee of: Novartis, Weibin Bao Shareholder of: Novartis, Employee of: Novartis, Corine Gaillez Shareholder of: Novartis and BMS, Employee of: Novartis, Iain McInnes Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer, and UCB.
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Schett, G., W. Chen, S. Gao, S. D. Chakravarty, M. Shawi, F. Lavie, E. Theander, M. Neuhold, L. Coates, and S. Siebert. "POS0308 EFFECT OF GUSELKUMAB ON SERUM BIOMARKERS IN PSORIATIC ARTHRITIS PATIENTS WITH INADEQUATE RESPONSE OR INTOLERANCE TO TUMOR NECROSIS FACTOR INHIBITORS: RESULTS FROM THE COSMOS STUDY." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 403.2–404. http://dx.doi.org/10.1136/annrheumdis-2022-eular.736.
Full textAbstract:
BackgroundGuselkumab (GUS), a selective IL-23 inhibitor, is efficacious in treating bio-naïve and TNFi-experienced active PsA patients (pts).1.2 In the COSMOS study of active PsA pts with lack of efficacy/intolerance, i.e., inadequate response (IR), to 1-2 TNFi, GUS demonstrated significantly greater response rates and mean improvements in PsA signs and symptoms vs. placebo (PBO) at Week (W) 24.3ObjectivesEvaluate baseline (BL) serum levels of pro-inflammatory biomarkers (CRP, serum amyloid A [SAA], TNFα, IFNɣ, IL-6, IL-10, IL-17F, IL-17A, IL-22) and their relationship to BL disease activity, GUS treatment (tx), and clinical response in COSMOS TNFi-IR pts.MethodsTNFi-IR pts ≥18 yrs with active PsA (≥3 swollen & ≥3 tender joint counts [SJC/TJC]) were randomized 2:1 to GUS 100 mg every 8 W (Q8W) through W44 or PBO with early escape (W16) or crossover (W24) to GUS Q8W. Samples for serum biomarker analyses, collected at W0, 4, 16, 24, and 48 from consenting pts, were compared with healthy controls (HC; independent of COSMOS). Associations between early biomarker changes and BL disease activity, GUS tx, and clinical response at W24 were assessed.ResultsAmong 285 COSMOS pts, 50/95 PBO and 100/190 GUS pts had available biomarker data. BL characteristics of the biomarker cohort were similar to the overall COSMOS population and well balanced across tx arms. At BL, levels of TNFα, IFNɣ, IL-6, IL-10, IL-17A, IL-17F, and IL-22 were significantly upregulated in TNFi-IR pts vs. HC (Table 1). IL-6, CRP, and SAA levels were associated with BL joint disease severity per Disease Activity Score (DAS) 28-CRP (but not with SJC [0-66]/TJC [0-68]). IL-17A and IL-17F levels were associated with BL PASI score. Through W24, significant decreases from BL in levels of CRP, SAA, IL-6, IL-17A, IL-17F, and IL-22 were seen in GUS-, but not PBO-tx pts. Reductions in IL-17A, IL-17F and IL-22 with GUS were significant by W4, decreased further by W16, and were sustained through W24 and W48. In GUS-tx pts, serum levels of IL-17F (from W16) and IL-22 (from W4) were not significantly different vs. HC. At W48, reductions in these same markers were seen in PBO-tx pts who crossed over to GUS at W16/24 (Figure 1; IL-17A, IL-17F, & IL-22 data shown). In these TNFi-IR pts, GUS-tx pts achieving ACR20 at W24 exhibited higher IL-22 and IFNɣ levels at BL than nonresponders (NR). All other biomarkers evaluated were not significantly associated with ACR20 response to GUS. In the subset of pts with IGA of psoriasis assessed, BL IL-6 and SAA levels were upregulated in W24 IGA 0/1 responders (R) vs. NR in the GUS arm. ACR20 and IGA 0/1 R at W24 exhibited an early greater reduction in IL-6 expression (at W4) than did respective NR in the GUS arm. No BL biomarkers were associated with ACR50 or PASI75 responses to GUS at W24.Table 1.Select Serum Biomarkers at BL in TNFi-IR pts vs. HC▫Biomarker, pg/mLHC N=24TNFi-IR N=150Fold differencep-valueCRP22.1 (1.5)22.8 (2.2)1.60.2895SAA21.7 (1.2)22.8 (2.4)2.10.0794IL-60.07 (1.1)0.98 (1.7)1.90.0314*IL-10-2.3 (1.1)-1.7 (1.0)1.50.0272*IL-17A-2.1 (1.3)-0.3 (1.5)3.3<0.0001*IL-17F0.05 (1.1)1.3 (1.5)2.40.0007*IL-221.9 (1.1)3.1 (1.3)2.40.0002*TNFα0.5 (0.75)1.4 (1.1)1.80.0002*IFNɣ2.4 (0.84)2.9 (1.3)1.50.0259*Data are mean (SD); *p<0.05 and |fold difference| >1.4; ▫adjusted for confounding factors age & sex.ConclusionGUS-tx TNFi-IR pts showed response-specific associations with BL biomarkers (IL-22, IFNɣ, IL-6, and SAA). GUS resulted in decreased levels of elevated CRP, SAA, IL-6, IL-17A, IL-17F, and IL-22, while no significant change was observed with PBO tx. Reductions in these biomarkers were evident as early as W4 and approximated levels seen in HC from W16 onward (W4 for IL-22), suggesting apparent normalization of effector cytokines associated with the IL-23/Th17 axis following GUS tx.References[1]Deodhar A et al. Lancet 2020;395:1115-25.[2]Mease PJ et al. Lancet 2020;395:1126-36.[3]Coates LC et al. doi:10.1136/annrheumdis-2021-220991.Disclosure of InterestsGeorg Schett Speakers bureau: Amgen, AbbVie, Bristol Myers Squibb, Eli Lilly, Gilead, Janssen, Novartis and UCB, Warner Chen Shareholder of: Janssen, Employee of: Janssen, Sheng Gao Shareholder of: Janssen, Employee of: Janssen, Soumya D Chakravarty Shareholder of: Janssen, Employee of: Janssen, May Shawi Shareholder of: Janssen, Employee of: Janssen, Frederic Lavie Shareholder of: Janssen, Employee of: Janssen, Elke Theander Shareholder of: Janssen, Employee of: Janssen, Marlies Neuhold Shareholder of: Janssen, Employee of: Janssen, Laura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Stefan Siebert Speakers bureau: AbbVie, Biogen, GSK, Janssen, Novartis, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, GSK, Janssen, Novartis, UCB
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Mease, P. J., E. Soriano, S. D. Chakravarty, E. Rampakakis, M. Shawi, P. Nash, and P. Rahman. "POS1030 PAIN RESPONSE IN PSORIATIC ARTHRITIS PATIENTS TREATED WITH GUSELKUMAB IS DRIVEN PREDOMINANTLY BY INFLAMMATION-INDEPENDENT EFFECTS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 828.1–828. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1384.
Full textAbstract:
BackgroundAlthough reducing inflammation has been associated with pain improvement, the two do not always correlate. Recent studies have suggested that, in addition to its role in inflammation pathogenesis, IL-23 may be involved in pain regulation in a lymphocyte-independent manner1. Guselkumab (GUS), a fully human monoclonal antibody that selectively inhibits IL-23, has demonstrated safety and efficacy in treating multiple domains of active PsA in the DISCOVER-1&2 (D1&D2) trials2,3.ObjectivesTo quantify the role of reducing inflammation on the observed relationship between GUS and pain response in PsA patients (pts) using mediation modelling.MethodsPooled data from the D1&D2 studies were analyzed. Pts in D1 had ≥3 swollen and ≥3 tender joints (SJC/TJC) and C-reactive protein (CRP)≥0.3 mg/dL; in D2, pts had ≥5 SJC and ≥5 TJC and CRP≥0.6 mg/dL. 31% of D1 pts received 1-2 prior tumor necrosis factor inhibitors (TNFi); D2 pts were bio-naïve. Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then every 8 weeks (Q8W); or placebo (PBO); PBO pts crossed over to GUS 100 mg Q4W at W24. Pts with history of fibromyalgia were excluded from the analysis. Least square mean changes in pt-reported pain (0-100 VAS) through W52 were estimated with a repeated measures linear mixed model adjusting for known pain determinants. Mediation modelling was performed separately for Q4W & Q8W, W4 & W24, and TNFi-naïve & -experienced (exp) pts. In each model, change in pt-reported pain was the dependent variable; treatment regimen was the independent variable; inflammation, measured by change in SJC or CRP, was the designated mediator; covariates were: age; sex; and baseline (BL) pain score, BMI, SF-36 MCS score, and NSAID use.ResultsMean (SD) BL pain levels in the GUS Q4W, GUS Q8W, and PBO groups were 60.4 (19.8), 62.0 (20.2), and 61.1 (19.6), respectively. Treatment with GUS was associated with significantly greater pain improvement compared with PBO as early as W4 (ΔQ4W-PBO [95%CI]: -4.9 [-7.6, -2.2]; ΔQ8W-PBO [95%CI]: -5.2 [-7.9, -2.5] (Figure 1). These between-group differences were further enhanced by W24 (ΔQ4W-PBO [95%CI]: -14.6 [-17.6, -11.5]; ΔQ8W-PBO [95%CI]: -14.3 [-17.3, -11.2]); by W52, GUS-randomized pts exhibited an approximate 30-point (̴50%) decrease in pain. Similar results were observed for TNFi-naïve and TNFi-exp pts.Figure 1.Mediation analyses demonstrated that the majority of GUS effect on pain at W4 was not attributable to SJC (direct effect), specifically ≤6% was mediated by inflammation as assessed by changes in SJC (indirect effect; Table 1). Similarly, at W24, the indirect effect via SJC improvement represented ≤10% of the GUS treatment effect. No differences were observed between TNFi-naïve and -exp pts at either timepoint.Consistent results were obtained when using CRP as the mediator variable instead of SJC, whereby ≤2-9%% of GUS effect on pan was mediated by inflammation and 91-98% was direct (Table 1).Table 1.Direct (D) Treatment Effect vs. Indirect (IND) Effect via Inflammation Markers on Pain ImprovementMediatorWeekPt GroupEffectGUS Q4WGUS Q8WSJC4AllD96.7%*97.0%*IND†3.3%3%TNFi-NaiveD93.7%*98.5%*IND†6.3%1.5%TNFi-ExpD100%*100%*IND†0%0%24AllD94.8%*92.0%*IND†5.2%*8.0%*TNFi-NaiveD89.6%*90.1%*IND†10.4%*9.9%*TNFi-ExpD99.8%*95.7%*IND†0.2%4.3%CRP4AllD97.6%*95.0%*IND‡2.4%5.0%TNFi-NaiveD98.2%*95.4%*IND‡1.8%4.6%TNFi-ExpD97.6%*95.3%*IND‡2.4%4.7%24AllD97.2%*94.2%*IND‡2.8%5.8%*TNFi-NaiveD98.1%*95.9%*IND‡1.9%4.1%TNFi-ExpD96.5%*91.4%*IND‡3.5%8.6%*p<0.05; †via SJC; ‡via CRPConclusionGUS induced significant improvement in pt-reported pain as early as W4 of treatment, which was continuously enhanced through W52. While the known mediation effect of SJC and CRP, as markers of inflammation, on pain was confirmed, the majority of GUS’s effect on pain reduction was independent of its effect on these markers, regardless of dosing regimen or prior TNFi experience.References[1]Arthritis Res Ther. 2020;22:123[2]Lancet. 2020;395:1115[3]Lancet. 2020;395:1126Disclosure of InterestsPhilip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Enrique Soriano Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Janssen, Novartis, and Roche, Grant/research support from: AbbVie, Janssen, Novartis, Pfizer, Roche, and UCB, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC and Drexel University College of Medicine, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Peter Nash Speakers bureau: Janssen, Abbvie, Pfizer, Novartis, Lilly, Gilead, Roche, Sandoz, Celgene, Sun, Boehringer, and Bristol Myers Squibb, Consultant of: Janssen, Abbvie, Pfizer, Novartis, Lilly, Gilead, Roche, Sandoz, Celgene, Sun, Boehringer, and Bristol Myers Squibb, Grant/research support from: Janssen, Abbvie, Pfizer, Novartis, Lilly, Gilead, Roche, Sandoz, Celgene, Sun, Boehringer, and Bristol Myers Squibb, Proton Rahman Speakers bureau: Janssen, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: Janssen and Novartis
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Orbai, A. M., L. C. Coates, A. Deodhar, P. Helliwell, C. T. Ritchlin, A. Kollmeier, E. C. Hsia, et al. "POS1029 GUSELKUMAB-TREATED PATIENTS WITH PSORIATIC ARTHRITIS ACHIEVED CLINICALLY MEANINGFUL IMPROVEMENTS IN GENERAL HEALTH OUTCOMES MEASURED WITH PROMIS-29 THROUGH 52 WEEKS: RESULTS FROM THE PHASE 3 DISCOVER-1 TRIAL." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 785–86. http://dx.doi.org/10.1136/annrheumdis-2021-eular.471.
Full textAbstract:
Background:In the DISCOVER-1 study, the interleukin-23 p19 subunit inhibitor guselkumab (GUS) demonstrated robust efficacy across joint and skin clinical manifestations of psoriatic arthritis (PsA).1 Patients (pts) with PsA also experience a broad range of symptoms that negatively impact health-related quality of life (eg, pain, fatigue, anxiety, depression, sleep disturbance, poor physical function).2Objectives:Assess the treatment effect of GUS on general health outcomes in pts with PsA in the DISCOVER-1 trial through Week (W) 52 using the Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) instrument.Methods:Pts with active PsA (≥3 swollen + ≥3 tender joints; C-reactive protein ≥0.3 mg/dL) and inadequate response to standard conventional therapies were randomized 1:1:1 to GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or placebo (PBO). PBO pts switched to GUS 100 mg Q4W at W24. PROMIS-29 contains 4 items for each of 7 domains (anxiety, depression, fatigue, pain interference, physical function, sleep disturbance, social participation) and 1 pain intensity item; 28 items are scored on a 5-point Likert-type scale, and pain intensity is rated from 0-10. The raw score of each domain is converted to a standardized T-score, with norms based on a general population mean score=50 and a standard deviation (SD)=10. Higher scores in anxiety, depression, fatigue, pain interference, and sleep disturbance indicate more severe symptoms; higher physical function and social participation scores indicate better health outcomes. Changes ≥5 points (1/2 SD of T-score) are considered clinically meaningful. Analyses were performed using both observed (mean scores/changes, effect sizes) and imputed (clinically meaningful response, whereby change from baseline was set to 0 at W24/52 for pts who had missing data or at W24 for pts who met treatment failure criteria prior to W24).Results:At baseline, mean PROMIS-29 T-scores for physical function, social participation, sleep disturbance, pain, and fatigue were worse in the 381 PsA pts enrolled in DISCOVER-1 than in the general US population. Across all 7 domains, observed mean PROMIS-29 T-scores showed improvements in GUS-treated pts from baseline to W24 and W52 (Figure 1). Observed mean changes from baseline to W24 and W52, with calculated effect size, are shown (Table 1). In all pts, including those with imputed data, significantly higher percentages of pts in both GUS treatment groups vs PBO had ≥5-point improvements in fatigue, pain interference, physical function, sleep disturbance, social participation, and pain intensity domains at W24 (all nominal p<0.05). Mean improvements in PROMIS-29 domains were maintained through W52.Conclusion:In pts with active PsA, PROMIS-29 results indicate that GUS treatment was associated with clinically meaningful reductions in fatigue and pain and improvement in physical function and social participation, which were maintained through 1 year.References:[1] Deodhar A et al. Lancet. 2020;395:1115-25.[2] Orbai A et al. Ann Rheum Dis. 2017;76:673-80.Table 1.Mean Change and Effect Size of Change From Baseline in PROMIS-29 Domain Scores at W24 and W52 (Observed)Mean Change From Baseline [Effect Size]GUS Q4WGUS Q8WPBOW0-24GUS Q4WW24-52W24W52W24W52W24W52Anxiety−3.1 [−0.3]−3.1 [−0.3]−3.7 [−0.4]−4.3 [−0.5]−1.5 [−0.2]−3.6 [−0.4]Depression−2.7 [−0.3]−3.0 [−0.4]−4.0 [−0.4]−4.0 [−0.4]−0.6 [−0.1]−2.5 [−0.3]Fatigue−4.8 [−0.5]−5.6 [−0.6]−4.8 [−0.5]−6.8 [−0.7]−2.1 [−0.2]−5.7 [−0.6]Pain interference−5.4 [−0.8]−6.2 [−1.0]−5.8 [−1.0]−7.0 [−1.1]−2.8 [−0.4]−6.3 [−1.0]Physical function5.0 [0.8]5.9 [0.9]4.1 [0.6]5.0 [0.7]1.7 [0.2]4.2 [0.6]Sleep disturbance−2.5 [−0.4]−3.9 [−0.6]−3.8 [−0.6]−4.4 [−0.6]−1.5 [−0.2]−3.3 [−0.5]Social participation4.2 [0.5]5.3 [0.7]5.3 [0.6]6.6 [0.8]1.7 [0.2]4.9 [0.6]Pain intensity*−2.3 [−1.2]−2.8 [−1.5]−2.1 [−1.1]−2.7 [−1.4]−0.7 [−0.4]−2.5 [−1.3]*Raw score; all other domains reported as T-score.Disclosure of Interests:Ana-Maria Orbai Consultant of: Eli Lilly, Janssen, Novartis, Pfizer, UCB, Grant/research support from: Abbvie, Eli Lilly and Company, Celgene, Novartis, Janssen, Horizon, Laura C Coates Consultant of: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Boehringer Ingelehim, Celgene, Domain, Eli Lilly, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Novartis, Pfizer, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GSK, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, and UCB, Philip Helliwell Consultant of: Galapagos, Janssen, and Novartis, Grant/research support from: Abbvie, Janssen, and Pfizer, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie, Amgen, UCB Pharma, Alexa Kollmeier Shareholder of: Johnson & Johnson, of which Janssen Research & Development, LLC is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, of which Janssen Research & Development, LLC is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, of which Janssen Research & Development, LLC is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Yusang Jiang Employee of: Cytel, Inc., providing statistical support (funded by Janssen), Yan Liu Shareholder of: Johnson & Johnson, of which Janssen Research & Development, LLC is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Chenglong Han Shareholder of: Johnson & Johnson, of which Janssen Research & Development, LLC is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC.
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Fan, Linda. "Experimental research and numerical simulation based on granary effect." Frontiers in Computing and Intelligent Systems 3, no. 2 (April 13, 2023): 96–98. http://dx.doi.org/10.54097/fcis.v3i2.7523.
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Based on Janssen model and discrete element model, experiment and numerical simulation are used to verify the granary effect of coal storage silo in power plant. In the experiment, the bottom pressure of two different particles in a variable-diameter cylinder is measured. The type of particles and the diameter of the cylinder are used as the research objects to explore the function relationship between the bottom pressure of the cylinder and the particle filling quality. In the experiment with soybeans as filling particles, the granary effect is more obvious, and the smaller the cylinder diameter is, the more obvious the granary effect is. At the same time, establish a mathematical model of particles, simulation of particle accumulation process, solve the force information of particles. Through numerical simulation, it is found that the data is more in line with the Janssen model, and the granary effect is more obvious.
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Siebert, S., L. Coates, G. Schett, S. P. Raychaudhuri, W. Chen, S. Gao, S. D. Chakravarty, et al. "POS0074 IMMUNOLOGICAL DIFFERENCES BETWEEN PsA PATIENTS WHO ARE TUMOR NECROSIS FACTOR INHIBITOR-NAIVE AND WHO HAVE INADEQUATE RESPONSE TO TUMOR NECROSIS FACTOR INHIBITORS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 254.2–255. http://dx.doi.org/10.1136/annrheumdis-2022-eular.892.
Full textAbstract:
BackgroundA better understanding of the immunological differences between psoriatic arthritis (PsA) patients (pts) who are tumor necrosis factor inhibitor (TNFi)-naïve & who have inadequate response to TNFi (TNFi-IR) may guide treatment choices. In DISCOVER-1, benefit of the IL-23p19 subunit inhibitor guselkumab (GUS) every-four-weeks (Q4W) & Q8W vs placebo (PBO) in improving PsA signs & symptoms was seen in adults with active PsA.1 The Ph3b COSMOS study of GUS Q8W vs PBO in TNFi-IR PsA pts corroborated these findings.2ObjectivesAssess baseline (BL) molecular differences between TNFi-naïve & -IR PsA pts & investigate GUS pharmacodynamic (PD) effect on cytokine expression over time in these cohorts.MethodsSerum samples collected from consenting biomarker substudy pts in DISCOVER-11 (TNFi-naïve [n=101] & -IR [n=17]), DISCOVER-23 (TNFi-naïve [n=150]), & COSMOS2 (TNFi-IR [n=76]) were analyzed for selected serum cytokine levels. TNFi-IR pts in this post-hoc analysis had active PsA & discontinued 1-2 TNFi due to inadequate efficacy; these pts required a TNFi-specific washout period prior to starting GUS. PD effect of GUS Q8W on cytokine levels was assessed. Differential BL cytokine expression, associations between BL cytokine levels & clinical response (Psoriasis [PsO] Area & Severity Index 75% improvement from BL [PASI75] & American College of Rheumatology 20% improvement [ACR20]), & GUS effect on cytokine levels were analyzed with a General linear model & Spearman linear regression.ResultsBL pt demographics, disease characteristics, & conventional synthetic disease-modifying antirheumatic drug (csDMARD) use were comparable between TNFi-naïve (DISCOVER-1 & -2, N=251) & -IR (DISCOVER-1 & COSMOS, N=93) pts, with differences in mean PASI score (8.9 v 12.5), swollen joint count (SJC) (11.7 v 10.3), PsA duration (5.8 v 9.8 yrs), & PsO duration (16.7 v 20.4 yrs; Table 1). BL serum IL-22 & TNFα levels for pooled treatment groups were higher in TNFi-IR than -naïve pts (p<0.05). At W24, GUS reduced IL-22, IL-17A/F, IL-6, C-reactive protein (CRP), & serum amyloid A protein to similar levels in both cohorts (p<0.05; Figure 1). W24 PASI75 responders had higher BL IL-17F levels with GUS in both cohorts (p<0.05) & higher IL-22 levels in TNFi-IR pts only (p<0.05). A trend of upregulated BL IL-22 expression in W24 ACR20 responders was seen for TNFi-IR pts with GUS (p=0.07).Table 1.BL demographics, disease characteristics, & drug use in TNFi-naïve & -IR cohorts with available cytokine data in DISCOVER-1&2 & COSMOS.*TNFi-naïve (N=251)TNFi-IR (N=93)Age [yrs]47.2 (11.3)48.5 (11.1)Female, n (%)132 (52.6)46 (49.5)Body mass index [kg/m2]29.6 (6.1)30.3 (6.4)Median (range) CRP [mg/dL]0.9 (0.0-12.9)1.0 (0.0-13.2)Log2 IL-22 / TNFα [pg/mL]2.0 (1.4) / 1.1 (0.6)2.5 (1.5) / 1.9 (1.2)Log2 IL-17A / F [pg/mL]-0.4 (1.5) / 1.7 (1.5)-0.1 (1.7) / 2.0 (1.6)SJC [0-66]11.7 (7.1)10.3 (8.3)TJC [0-68]20.3 (13.1)20.6 (14.2)PsA duration [yrs]5.8 (5.9)9.8 (8.2)PsO duration [yrs]16.7 (12.8)20.4 (12.0)PsO Body surface area (%)14.8 (18.6)19.1 (21.3)Investigator’s Global Assessment score [0-4]2.3 (0.9)2.3 (1.0)PASI score [0-72]8.9 (10.6)12.5 (12.0)Enthesitis [Y], n (%)160 (63.7)58 (62.4)csDMARD use [Y], n (%)164 (65.3)62 (66.7)Corticosteroid use (Y), n (%)45 (17.9)19 (20.4)Methotrexate use [Y], n (%)136 (54.2)54 (58.1)Data are mean (SD) unless otherwise noted. *Pts with serum CRP level ≥0.3 mg/dL, SJC ≥3, & TJC ≥3 (to mimic D1 inclusion criteria1). TJC= tender joint countConclusionElevated BL IL-22 expression & association between BL IL-22 levels & W24 PASI75 response, & a W24 trend for an association between upregulated BL IL-22 & ACR20 response, in TNFi-IR pts seen in this exploratory analysis may suggest increased involvement of the IL-23 pathway in TNFi-IR pts. GUS showed comparable & significant PD effects for TNFi-naïve & -IR pts, consistent with observed clinical responses.References[1]Deodhar A, et al. Lancet. 2020;395:1115-25.[2]Coates LC, et al. Ann Rheum Dis. 2021;80:140-1.[3]Mease P, et al. Lancet. 2020;395:1126-36.Disclosure of InterestsStefan Siebert Speakers bureau: AbbVie, Biogen, GSK, Janssen, Novartis, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, GSK, Janssen, Novartis, and UCB, Laura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Georg Schett Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Gilead, Janssen, Novartis, and UCB, Siba P Raychaudhuri Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Warner Chen Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC (a wholly owned subsidiary of Johnson & Johnson), Sheng Gao Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC (a wholly owned subsidiary of Johnson & Johnson), Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC (a wholly owned subsidiary of Johnson & Johnson), May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Frederic Lavie Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Elke Theander Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC (a wholly owned subsidiary of Johnson & Johnson), Marlies Neuhold Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC (a wholly owned subsidiary of Johnson & Johnson), Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC (a wholly owned subsidiary of Johnson & Johnson), Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC (a wholly owned subsidiary of Johnson & Johnson), Proton Rahman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: Janssen and Novartis, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, and UCB
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Mease, P. J., P. Helliwell, D. D. Gladman, D. Poddubnyy, X. Baraliakos, S. D. Chakravarty, A. Kollmeier, et al. "POS1037 EFFECT OF GUSELKUMAB, A SELECTIVE IL-23p19 INHIBITOR, ON AXIAL-RELATED ENDPOINTS IN PATIENTS WITH ACTIVE PsA: RESULTS FROM A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY THROUGH 2 YEARS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 832.2–833. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1691.
Full textAbstract:
BackgroundGuselkumab (GUS), a selective IL-23p19 inhibitor, showed greater mean improvements in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores vs placebo (PBO) at Week (W) 24 in patients (pts) with active PsA and investigator-confirmed sacroiliitis in pooled post hoc analyses of data from phase 3 DISCOVER (D)-1&2 trials. Improvements in symptoms of axial involvement were maintained through 1 year.1ObjectivesTo assess maintenance of GUS effect on symptoms of axial involvement in biologic-naïve PsA pts with investigator-confirmed sacroiliitis through 2 years of D-2.MethodsIn D-2, 739 bio-naïve pts with active PsA (≥5 swollen + ≥5 tender joints, CRP ≥0.6 mg/dL despite standard therapies) were randomized 1:1:1 to GUS 100 mg every 4W (Q4W; n=245), GUS 100 mg at W0, W4, then Q8W (n=248), or PBO (n=246) with PBO→GUS 100 mg Q4W at W24. Pts with investigator-identified axial symptoms and sacroiliitis (prior X-ray or MRI, or pelvic X-ray at screening) were evaluated. Efficacy was assessed by changes in BASDAI, modified BASDAI (mBASDAI, excluding Q3 [peripheral joint pain]), and BASDAI Q2 (Spinal Pain) scores, and proportions of pts achieving BASDAI 50, Spinal Pain score ≤2, and AS Disease Activity Score (ASDAS) responses through W100. Through W24, pts who met treatment failure criteria or had missing data were considered nonresponders. After W24, missing data were imputed as nonresponse for binary endpoints or no change from baseline for continuous endpoints (nonresponder imputation [NRI]). Axial-related outcomes were also summarized by HLA-B27 status (+/-).Results246 pts had investigator-confirmed sacroiliitis. Baseline characteristics were similar across treatment groups (62% male; mean age 44.4 years; mean BASDAI scores 6.5-6.6). At W24, LS mean/mean changes in BASDAI (-2.4/-2.6) and ASDAS (-1.3/-1.5) scores were greater in GUS- vs PBO-treated pts. Improvements were maintained through W100 in GUS-treated pts: BASDAI, -3.1; Spinal Pain, -3.1; mBASDAI, -3.1; ASDAS, -1.7. Response patterns were similar for BASDAI 50 response rates in GUS-treated pts (W24 38-40%; W100 49-54%). At W24, GUS-treated pts had higher response rates for achievement of ASDAS inactive disease, major improvement, and clinically important improvement vs PBO; response rates (NRI) were maintained, or in some cases further increased, at 2 years. Results were consistent for achievement of ASDAS LDA and Spinal Pain score ≤2 (data not shown). GUS-related improvements in axial symptoms through W100 were generally consistent in HLA-B27+/- pts (data not shown).ConclusionIn bio-naïve pts with active PsA and investigator-confirmed sacroiliitis, GUS provided durable improvements in axial symptoms through W100, with substantial proportions of pts achieving and maintaining clinically meaningful improvements.References[1]Mease PJ et al. Lancet Rheumatol 2021;3:e715-723Table 1.Axial symptom assessments through W100 in PsA pts with investigator-confirmed sacroiliitis in DISCOVER-2 (NRI)GUS Q4W N=82GUS Q8W N=68PBO→GUS Q4W N=96Change in BASDAI scoreW24, LS mean (95% CI)-2.5 (-2.9, -2.0)-2.4 (-3.0, -1.8)-1.2 (-1.7, -0.7)Mean (SD)-2.5 (2.0)-2.6 (2.4)-1.4 (2.4)W52, mean (SD)-2.9 (2.3)-2.7 (2.5)-2.9 (2.6)W100, mean (SD)-3.0 (2.3)-3.1 (2.6)-3.3 (2.6)Change in mBASDAI (excludes Q3) scoreW24, LS mean (95% CI)-2.4 (-2.9, -1.9)-2.4 (-2.9, -1.8)-1.2 (-1.7, -0.7)Mean (SD)-2.5 (2.1)-2.6 (2.5)-1.3 (2.3)W52, mean (SD)-2.7 (2.6)-2.6 (2.5)-2.9 (2.4)W100, mean (SD)-3.3 (2.6)-3.1 (2.6)-3.0 (2.4)Change in Spinal Pain (BASDAI Q2) scoreW24, LS mean (95% CI)-2.2 (-2.7, -1.7)-2.3 (-2.9, -1.7)-0.9 (-1.5, -0.4)Mean (SD)-2.3 (2.6)-2.5 (2.8)-1.1 (2.5)W52, mean (SD)-2.6 (2.7)-2.5 (2.7)-2.5 (2.7)W100, mean (SD)-2.8 (2.7)-3.1 (2.8)-3.0 (2.8)Change in ASDAS scoreW24, LS mean (95% CI)-1.3 (-1.6, -1.1)-1.3 (-1.6, -1.1)-0.6 (-0.8, -0.4)Mean (SD)-1.4 (1.0)-1.5 (1.2)-0.7 (1.1)W52, mean (SD)-1.5 (1.1)-1.5 (1.3)-1.5 (1.3)W100, mean (SD)-1.6 (1.2)-1.7 (1.2)-1.6 (1.2)Disclosure of InterestsPhilip J Mease Speakers bureau: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Philip Helliwell Speakers bureau: AbbVie, Janssen, and Novartis, Consultant of: Eli Lilly, Janssen, and Pfizer, Dafna D Gladman Consultant of: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Abbvie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Denis Poddubnyy Consultant of: AbbVie, Eli Lilly, GlaxoSmithKline, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, MDS, Novartis, and Pfizer, Xenofon Baraliakos Speakers bureau: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Stephen Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, and UCB Pharma, Employee of: Imaging Rheumatology BV, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Glaxo Smith & Kline, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, Glaxo Smith & Kline, Novartis, Pfizer, and UCB
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Ritchlin, C. T., P. J. Mease, W. H. Boehncke, J. Tesser, E. Schiopu, S. D. Chakravarty, A. Kollmeier, et al. "AB0526 SUSTAINED GUSELKUMAB RESPONSE IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS REGARDLESS OF BASELINE DEMOGRAPHIC AND DISEASE CHARACTERISTICS: POOLED RESULTS THROUGH WEEK 52 OF TWO PHASE 3, RANDOMIZED, PLACEBO-CONTROLLED STUDIES." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1291–92. http://dx.doi.org/10.1136/annrheumdis-2021-eular.437.
Full textAbstract:
Background:In the Phase 3 DISCOVER-11 & DISCOVER-22 trials, guselkumab (GUS), a human monoclonal antibody targeting the IL-23p19-subunit, was effective in psoriatic arthritis (PsA) across joint & skin endpoints. At Week 24 (W24), GUS benefit was consistent regardless of baseline (BL) demographic & disease characteristics.3Objectives:We assessed whether GUS efficacy was sustained through W52 in pooled DISCOVER-1 & -2 patients (pts) across select BL subgroups.Methods:Adults with active PsA despite standard therapies were enrolled in DISCOVER-1 (swollen [SJC] ≥3 & tender joint count [TJC] ≥3, C-reactive protein [CRP] ≥0.3 mg/dL) & DISCOVER-2 (SJC ≥5 & TJC ≥5, CRP ≥0.6 mg/dL). 31% of DISCOVER-1 pts had received 1-2 prior tumor necrosis factor inhibitors; DISCOVER-2 pts were biologic naïve. Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or placebo (PBO). Pts randomized to PBO received GUS 100 mg Q4W starting at W24 & were excluded from these analyses assessing maintenance of effect from W24 to W52. GUS effects on joint (American College of Rheumatology [ACR]20/50/70) & skin (Investigator’s Global Assessment [IGA=0/1 + ≥2-grade reduction from W0] in pts with ≥3% body surface area [BSA] with psoriasis & IGA ≥2 at W0) endpoints were evaluated by pt BL SJC, TJC, conventional synthetic disease-modifying antirheumatic drug (csDMARD) use, body mass index (BMI), PsA duration, & % BSA with psoriasis. Missing data were imputed as nonresponse through W52.Results:BL pt characteristics in DISCOVER-1 (N=381) & DISCOVER-2 (N=739) were well balanced across randomized groups.1,2 Among 1120 pooled pts, mean SJC was 11, mean TJC was 21, & 68% used csDMARDs (primarily methotrexate [MTX]). At W24, 62% (232/373) & 60% (225/375), respectively, of GUS Q4W- & Q8W-treated pts achieved ACR20 vs 29% (109/372) of PBO, with GUS effect consistently observed across pt BL subgroups (Figure 1). ACR20 response rates were sustained or increased at W52 in the GUS Q4W (72%) & Q8W (70%) groups & across SJC (61-79%), TJC (68-76%), & csDMARD use (68-80%) subgroups (Table 1) & pt subgroups defined by BL BMI, PsA duration, & % BSA with psoriasis (data not shown). ACR50 & 70 response patterns were similar to ACR20 (Table 1). In pts with ≥3% BSA psoriasis & IGA ≥2 at BL, 71% (193/273) & 66% (171/258) of GUS Q4W- & Q8W-treated pts, respectively, vs 18% (47/261) of PBO, achieved IGA 0/1 at W24, with GUS effect consistently observed across pt BL subgroups (Figure 1). IGA 0/1 response rates were also sustained or increased at W52 in the GUS Q4W (80%) & Q8W (71%) groups & across % BSA with psoriasis (67-87%) & csDMARD use (68-87%) subgroups (Table 1) & pt subgroups defined by BL BMI and PsA duration (data not shown).Conclusion:Treatment with GUS 100 mg Q4W & Q8W resulted in sustained improvement in signs & symptoms of active PsA through W52 regardless of pt BL characteristics.References:[1]Deodhar A, et al. Lancet 2020;395:1115-25;[2]Mease P, et al. Lancet 2020;395:1126-36;[3]Deodhar A, et al. American College of Rheumatology 2020; Poster P0908.Figure 1Figure 1Table 1.ACR & IGA Responses at Weeks 24 & 52 & by Select BL CharacteristicsGuselkumab Q4WGuselkumab Q8WN=373N=375Week 24Week 52Week 24Week 52ACR20, %62726070 SJC (<10/10-15/>15)68/59/5379/61/6757/66/6068/68/76 TJC (<10/10-15/>15)74/67/5673/76/6962/60/6075/68/68 csDMARD use (none/any/MTX)66/60/6380/68/6862/59/5773/68/68ACR50, %34493145 SJC (<10/10-15/>15)41/32/2058/39/3834/28/2646/40/49 TJC (<10/10-15/>15)51/41/2458/53/4340/33/2652/46/43 csDMARD use (none/any/MTX)36/33/3553/46/4836/29/2751/42/40ACR70, %16271627 SJC (<10/10-15/>15)22/10/732/20/2418/10/1930/23/26 TJC (<10/10-15/>15)29/19/934/32/2227/15/1435/28/24 csDMARD use (none/any/MTX)21/13/1430/26/2721/14/1434/24/23N=273N=258IGA 0/1, %71806671 BSA % with psoriasis(≥3-<10/≥10-<20/≥20)61/71/8076/87/7962/64/7267/72/74 csDMARD use (none/any/MTX)84/64/6787/77/7872/63/6477/68/68Disclosure of Interests:Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, and UCB Pharma, Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN, and UCB Pharma, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB Pharma, Wolf-Henning Boehncke Speakers bureau: AbbVie, Almirall, Celgene, Janssen, Leo, Eli Lilly, Novartis, UCB Pharma, Consultant of: AbbVie, Almirall, Celgene, Janssen, Leo, Eli Lilly, Novartis, UCB Pharma, Grant/research support from: Pfizer, John Tesser Speakers bureau: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Crescendo Biosciences/Myriad, GlaxoSmithKline, Genentech, Janssen, Eli Lilly, and Pfizer, Consultant of: AbbVie, AstraZeneca, Bristol Myers Squibb, Gilead, Janssen, Eli Lilly, Novartis, and Pfizer, Grant/research support from: AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Horizon, Janssen, Eli Lilly, Merck KG, Novartis, Pfizer, Sandoz, Sun Pharma, Setpoint, and UCB Pharma, Elena Schiopu Consultant of: Janssen, Grant/research support from: Janssen, Soumya D Chakravarty Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Scientific Affairs, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, May Shawi Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Global Services, LLC, Yusang Jiang Employee of: Cytel, Inc., providing statistical support (funded by Janssen), Shihong Sheng Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Joseph F. Merola Consultant of: AbbVie, Arena, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma, Iain McInnes Consultant of: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma, Grant/research support from: Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, and UCB Pharma, Atul Deodhar Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, UCB Pharma.
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Baraliakos, X., M. Østergaard, D. Poddubnyy, D. Van der Heijde, A. Deodhar, P. Machado, V. Navarro-Compán, et al. "OP0059 EFFECT OF SECUKINUMAB VERSUS ADALIMUMAB BIOSIMILAR ON RADIOGRAPHIC PROGRESSION IN PATIENTS WITH RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS: A RANDOMISED PHASE IIIB STUDY." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 38.2–40. http://dx.doi.org/10.1136/annrheumdis-2023-eular.301.
Full textAbstract:
BackgroundLimited data exist on the effect of biologics in slowing radiographic progression in patients (pts) with radiographic axial spondyloarthritis (r-axSpA). Two-year data from MEASURE 1 showed low radiographic progression with secukinumab (SEC).[1]ObjectivesTo compare the effect of SEC vs adalimumab biosimilar (SDZ-ADL) on spinal radiographic progression from SURPASS,[2,3]the first head-to-head study in r-axSpA.MethodsIn this phase IIIb study, bio-naïve pts with active r-axSpA with a BASDAI ≥4, spinal pain score ≥4 (range 0–10), total back pain score ≥40 mm (range 0–100 mm), and with hs-CRP ≥5 mg/L or ≥1 syndesmophyte(s) on spinal radiograph were randomised (1:1:1) to SEC (150/300 mg; dose-blinded) or SDZ-ADL (40 mg; open label). Radiographs and MRIs were reviewed by 3 independent central readers (no adjudication performed) blinded to treatment and chronology of images. Primary endpoint was the proportion of pts with no radiographic progression (change from baseline [CFB] in modified Stoke AS Spinal Score [mSASSS] ≤0.5) on SEC vs SDZ-ADL at week (wk) 104 (superiority testing). Secondary endpoints included CFB-mSASSS at wk 104, proportion of pts with ≥1 syndesmophyte(s) at baseline (BSL) with no new syndesmophytes(s) at wk 104, CFB-MRI Berlin sacroiliac joint (SIJ) inflammation score, CFB-AS Spine MRI-activity (ASspiMRI-a) Berlin modification score, and safety.ResultsOverall, 859 pts received SEC 150 mg (n=287), 300 mg (n=286), or SDZ-ADL (n=286). With 78.5% male, mean age 42.1 years, mSASSS 16.6, BASDAI 7.1, hsCRP 20.4 mg/L, and 73% with ≥1 syndesmophyte(s), this population had high risk of radiographic progression. At wk 104, cumulative distribution of CFB-mSASSS was similar across arms (Figure 1). Proportion of pts with no radiographic progression was 66.1%, 66.9%, and 65.6% (P=ns, both SEC doses) while mean CFB-mSASSS was 0.54, 0.55, and 0.72 with SEC 150 mg, 300 mg, and SDZ-ADL. Overall, 56.9%, 53.8%, and 53.3% of pts in SEC 150 mg, 300 mg, and SDZ-ADL arms, with a BSL ≥1 syndesmophyte(s) did not develop new syndesmophyte(s) by wk 104 (Table 1). In the MRI sub-set (N=418), mean SIJ scores at BSL and wk 16 were 2.54 and 0.98 (SEC 150 mg), 1.96 and 0.92 (SEC 300 mg), and 1.59 and 0.38 (SDZ-ADL); corresponding spine scores were 3.50 and 1.79, 2.56 and 1.25, and 3.00 and 0.71.ConclusionSpinal radiographic progression over 2 years was low with no significant difference between SEC and SDZ-ADL arms. No new safety signals were identified.References[1]Braun J et al.Ann Rheum Dis. 2017;76(6):1070-77[2]Baraliakos X et al.Clin Drug Investig.2020;40(3):269-78[3]Baraliakos X et al.Arthritis Rheumatol.2022;74 (suppl 9)Table 1.Radiographic assessments at wk 104No radiographic progression*Treatment groupnNo progression rate (%)Estimated mean (95% CI)Marginal difference (95% CI)†NominalP-valueSEC 150 mg28366.166.63(60.73, 72.54)1.51(−6.63, 9.64)0.716SEC 300 mg28066.966.80(60.45, 73.14)1.67(−6.61, 9.95)0.693SDZ-ADL 40 mg28365.665.13(58.77, 71.49)--Change from BSL in mSASSS#Treatment groupnWithin treatmentTreatment contrast in LS mean†LS mean (SE)LS mean (SE)95% CISEC 150 mg2830.54 (0.18)−0.18 (0.24)−0.65, 0.29SEC 300 mg2800.55 (0.18)−0.16 (0.24)−0.64, 0.32SDZ-ADL 40 mg2830.72 (0.18)--No new syndesmophytes*‡Treatment groupn (%)‡Pts with no new syndesmophyte(s) (%)Estimated mean (95% CI)Marginal difference (95% CI)†SEC 150 mg211(73.5)56.957.22(50.16, 64.28)4.32(−5.62, 14.27)SEC 300 mg204(71.3)53.853.98(46.19, 61.78)1.09(−9.13, 11.31)SDZ-ADL 40 mg212(74.1)53.352.89(45.54, 60.24)-SEC 150 mg, N=287; SEC 300 mg, N=286; SDZ-ADL 40 mg, N=286.*Estimated mean, marginal difference, 95% CI, and p-value are from logistic regression model with treatment as a factor and BSL mSASSS score/count of vertebral corners with syndesmophyte as covariate using marginal standardisation method.#LS Mean and 95% CI are from ANCOVA model with treatment as a factor and BSL mSASSS score as covariate.†Comparison vs SDZ-ADL 40 mg.‡pts with syndesmophyte(s) at BSLAcknowledgements:NIL.Disclosure of InterestsXenofon Baraliakos Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB, Consultant for: AbbVie, BMS, Celgene, Chugai, Galapagos, Merck, Novartis, Pfizer, UCB, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Contocor, Eli-Lilly, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Schering-Plough, Takeda, UCB and Wyeth, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Contocor, Eli-Lilly, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Schering-Plough, Takeda, UCB and Wyeth, Grant/research support from: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Contocor, Eli-Lilly, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Schering-Plough, Takeda, UCB and Wyeth, Denis Poddubnyy Speakers bureau: AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, UCB, Consultant of: AbbVie, Biocad, BMS, Eli Lilly, Gilead, MSD, Novartis, Pfizer, Samsung Bioepis, UCB, Grant/research support from: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, Désirée van der Heijde Consultant of: Personal fees from Novartis, AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Pfizer, UCB Pharma, and Director of Imaging Rheumatology bv, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Aurinia, Bristol-Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, Moonlake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, Novartis, Pfizer, and UCB, Pedro Machado Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, Consultant of: Abbvie, BMS, Celgene, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, Victoria Navarro-Compán Speakers bureau: Abbvie, BMS, Eli Lilly, Galapagos, Janssen, Moonlake, MSD, Novartis, Pfizer, Roche and UCB, Consultant of: Abbvie, BMS, Eli Lilly, Galapagos, Janssen, Moonlake, MSD, Novartis, Pfizer, Roche and UCB, Kay-Geert Hermann Consultant of: AbbVie, lecture fees from MSD, Novartis, Pfizer. Co-founder of BerlinFlame GmbH, Mitsumasa Kishimoto Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Celgene, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB Pharma (consulting fees and/or honoraria), Eun Young Lee Consultant of: Immonoforge and IMbiologics, Lianne S. Gensler Consultant of: Gilead, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer and UCB, Grant/research support from: Novartis, UCB, and Pfizer, Uta Kiltz Consultant of: AbbVie, Biocad, Biogen, Chugai, Eli Lilly, Fresenius, Grünenthal, GSK, Hexal, Janssen, MSD, Novartis, Pfizer, Roche and UCB, Grant/research support from: AbbVie, Biocad, Biogen, Chugai, Eli Lilly, Fresenius, GSK, Grünenthal, Hexal, Janssen, MSD, Novartis, Pfizer, Roche and UCB, Marco Eigenmann Shareholder of: Novartis, Employee of: Novartis, Patricia Pertel Shareholder of: Novartis, Employee of: Novartis, Aimee Readie Shareholder of: Novartis, Employee of: Novartis, Hanno Richards Shareholder of: Novartis, Employee of: Novartis, Brian Porter Shareholder of: Novartis, Employee of: Novartis, Juergen Braun Consultant of: Personal fees from: Abbvie, Amgen, Boehringer, Celltrion, MSD, Novartis, UCB, and Eli Lilly.
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Smolen, J. S., T. Korotaeva, M. Nurmohamed, S. Siebert, P. Bergmans, K. De Vlam, E. Gremese, et al. "AB0530 EFFECT OF SKIN SYMPTOMS ON DISEASE IMPACT IN PATIENTS WITH PSORIATIC ARTHRITIS RECEIVING THE IL-12/23 INHIBITOR USTEKINUMAB OR TNF INHIBITORS IN THE REAL-WORLD PSABIO STUDY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1295–96. http://dx.doi.org/10.1136/annrheumdis-2021-eular.767.
Full textAbstract:
Background:Psoriatic arthritis (PsA) is characterised by musculoskeletal symptoms, and patients (pts) with PsA usually experience psoriasis concurrently. Real-world data reflecting impact of skin symptoms on PsA disease burden are limited.Objectives:Analyse effectiveness of ustekinumab (UST) and tumour necrosis factor inhibitor (TNFi) therapy on extent of skin involvement, and the impact this has on PsA disease burden and drug persistence.Methods:PsABio (NCT02627768) is a prospective, observational study of 1st/2nd/3rd-line UST or TNFi treatment in PsA in 8 European countries. Extent of skin involvement was categorised as body surface area (BSA): clear/almost clear; <3% but not clear/almost clear; 3–10%; or >10%. Pt-reported disease impact was evaluated by PsAID-12, including assessment of two skin-related domains (D): D3 (skin problems, including itching) and D10 (embarrassment and/or shame because of appearance). Estimated persistence at 1 year was assessed across baseline (BL) BSA categories.Results:At BL, significantly more pts receiving UST than TNFi had BSA >10% (Figure 1). BL disease impact (PsAID-12) was worse in pts with BSA >10% than <3% in D3, D10 and total (non-overlapping 95% CIs suggest significance) (Table 1). BSA improved from BL to 1 year with both treatments. At 1 year, 64% of pts in both groups had clear/almost clear skin and only 3% had BSA >10% (Figure 1). At 1 year, both treatments significantly reduced disease impact (PsAID-12 total), and D3 and D10 scores, irrespective of BL BSA category, but most markedly in pts with higher BL BSA (Table 1). Worse BL psoriasis was generally associated with longer persistence for both treatments; however, at 1 year, pts with BSA >10% had significantly shorter persistence with TNFi (mean [95% CI]: 361 [336; 387] days) than with UST (410 [394; 426] days).Conclusion:In PsA, interleukin-12/23 inhibition (UST) and TNFi therapy in routine care rapidly and substantially reduced extent of skin involvement and related disease impact. Pts with highest BL skin involvement had significantly longer drug persistence with UST than with TNFi. Together, PsABio data suggest that successful treatment of skin involvement in PsA with biologics reduces disease burden and may improve persistence, especially in pts with worse BL psoriasis.Figure 1Table 1.PsAID-12 scores at BL and change from BL scores at 6 months and 1 year, by BL BSA categoryMean (95% CI)Domain 3(skin problems, including itching)Domain 10(embarrassment and/orshame because of appearance)Total PsAID-12USTTNFiUSTTNFiUSTTNFiPsAID-12 score at BL by BL BSA <3%4.2 (3.7; 4.8)3.1 (2.7; 3.6)3.9 (3.3; 4.4)3.1(2.6; 3.6)5.7(5.3; 6.0)5.0 (4.6; 5.3) 3–10%6.4 (5.9; 6.8)5.8 (5.3; 6.3)4.1 (3.5; 4.7)4.5 (3.9; 5.1)5.4 (5.1; 5.8)5.8 (5.4; 6.1) >10%7.9 (7.5; 8.3)6.7 (6.0; 7.5)6.1 (5.4; 6.8)5.8 (4.8; 6.8)6.2 (5.7; 6.6)6.1 (5.6; 6.7)Change from BL in PsAID-12 score at 6 months by BL BSA <3%-1.5 (-2.1; -0.9)-0.8 (-1.3; -0.3)-1.5 (-2.0; -0.9)-1.2 (-1.6; -0.7)-1.6 (-2.0; -1.2)-1.9 (-2.2; -1.5) 3–10%-3.2 (-3.8; -2.7)-2.4 (-3.0; -1.9)-1.9 (-2.5; -1.3)-2.0 (-2.5; -1.5)-2.0 (-2.4; -1.6)-2.4 (-2.8; -2.0) >10%-4.2 (-4.9; -3.6)-2.5 (-3.2; -1.9)-2.9 (-3.5; -2.2)-1.6 (-2.4; -0.8)-2.4 (-2.8; -2.0)-2.2 (-2.7; -1.7)Change from BL in PsAID-12 score at 1 year (LOCF) by BL BSA <3%-1.5 (-2.1; -0.9)-0.8 (-1.3; -0.3)-1.6 (-2.2; -1.1)-1.2 (-1.7; -0.7)-1.6 (-2.0; -1.2)-1.9 (-2.3; -1.5) 3–10%-3.5 (-4.0; -2.9)-3.2(-3.7; -2.7)-2.0 (-2.6; -1.4)-2.5 (-3.0; -2.0)-2.2 (-2.6; -1.7)-3.0 (-3.4; -2.6) >10%-4.9 (-5.5; -4.3)-3.1 (-4.0; -2.3)-3.5 (-4.2; -2.8)-2.7 (-3.7; -1.8)-2.9 (-3.4; -2.4)-2.9 (-3.5; -2.2)PsAID-12 total score ≤4 is considered a patient-acceptable symptom state.BL, baseline; BSA, body surface area; CI, confidence interval; LOCF, last observation carried forward; PsAID-12, 12-item Psoriatic Arthritis Impact of Disease questionnaire; TNFi, tumour necrosis factor inhibitor; UST, ustekinumabAcknowledgements:This study was funded by Janssen.Disclosure of Interests:Josef S. Smolen Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, MSD, Novartis- Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB, Grant/research support from: AbbVie, AstraZeneca, Lilly, Novartis, Roche, Tatiana Korotaeva Speakers bureau: AbbVie, Amgen, Biocad, Janssen, Lilly, MSD, Novartis, Novartis-Sandoz, Pfizer, UCB, Consultant of: AbbVie, Amgen, Biocad, Janssen, Lilly, MSD, Novartis, Novartis-Sandoz, Pfizer, UCB, Grant/research support from: Pfizer, Michael Nurmohamed Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi, UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi, UCB, Stefan Siebert Speakers bureau: AbbVie, Amgen (previously Celgene), Biogen, Janssen, Novartis, UCB, Consultant of: AbbVie, Janssen, UCB, Grant/research support from: Amgen (previously Celgene), Boehringer Ingelheim, Bristol-Myers Squibb, GSK, Janssen, Novartis, Pfizer, UCB, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Kurt de Vlam Speakers bureau: AbbVie, Amgen, Eli Lilly, Novartis, UCB, Paid instructor for: Amgen, Galapagos, UCB, Consultant of: Eli Lilly, Galapagos, Johnson & Johnson, Novartis, UCB, Grant/research support from: Celgene, Elisa Gremese: None declared., Beatriz Joven-Ibáñez Speakers bureau: AbbVie, Celgene, Janssen, Novartis, MSD, Pfizer, Wim Noel Employee of: Janssen, Petros Sfikakis Consultant of: AbbVie, Actelion, Boehringer Ingelheim, Enorasis, Farmaserv-Lilly, Genesis, Gilead, MSD, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Faran, Janssen, Pfizer, Roche, Elke Theander Employee of: Janssen, Laure Gossec Consultant of: AbbVie, Amgen, Bioepis, Biogen, Bristol-Myers Squibb, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Sanofi-Aventis, UCB, Grant/research support from: Amgen, Galapagos, Janssen, Lilly, Pfizer, Sandoz, Sanofi.
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Nash, P., C. T. Ritchlin, P. Rahman, M. Shawi, E. Rampakakis, Y. Lee, A. Kollmeier, et al. "POS1070 BASELINE DETERMINANTS OF PAIN RESPONSE IN PATIENTS WITH PSORIATIC ARTHRITIS RECEIVING GUSELKUMAB." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 858.2–859. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1158.
Full textAbstract:
BackgroundPain in patients (pts) with psoriatic arthritis (PsA) has multifaceted origins; sustained improvement is difficult to achieve.1 Guselkumab (GUS), a fully human monoclonal antibody that selectively inhibits IL-23, is effective in treating multiple domains of PsA including joint, skin, and entheseal symptoms, and also elicits long-lasting improvements in pt-reported pain in the DISCOVER-1&2 trials of pts with active PsA.2ObjectivesThese post hoc analyses were conducted to identify determinants of changes in pt-reported pain in PsA pts using pooled data through 1 year of DISCOVER-1&2.MethodsEnrolled adult pts had active PsA despite standard therapies. DISCOVER-1 pts had ≥3 swollen and ≥3 tender joints and C-reactive protein (CRP) ≥0.3 mg/dL; DISCOVER-2 pts had ≥5 swollen and ≥5 tender joints and CRP ≥0.6 mg/dL. 31% of DISCOVER-1 pts received 1-2 prior tumor necrosis factor inhibitors; DISCOVER-2 pts were biologic-naïve. Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (wks) (Q4W); GUS 100 mg at W0, W4, then every 8 wks (Q8W); or placebo (PBO); PBO pts crossed over to GUS 100 mg Q4W at W24. Determinants with a statistically important effect (p<0.15) on pain (0-100 mm Visual Analogue Scale) in univariate Repeated Measures Generalized Linear Mixed Effects Models were included in a multivariate model employing backward stepwise selection (Pout=0.1) to identify independent determinants of pain improvement over 24 wks; the model was then tested separately in pts treated with PBO (through W24) and with GUS (through W24 and through W52).ResultsGUS was associated with significantly greater improvement in pain compared to PBO as early as 2 wks post-treatment; there was a significant interaction between treatment group and time, with effect of GUS on pain continuously enhanced through W24. Higher baseline (BL) pain score, worse mental health (assessed with the Short-Form-36 Mental Component Summary [SF-36 MCS] score), and lower fatigue level and lower tender joint count [TJC] were also associated with significantly greater pain improvements at W24, while background use of NSAIDs was a negative predictor of pain improvement (Table 1). Treatment effect on pain was independent of PsA duration, gender, PsA subtype, prior TNFi exposure, BL skin disease, and BL swollen joint count (SJC). Continuous significant improvement from BL in pain with GUS extended through W52 even after adjustment for the identified determinants of pain improvement through W24 (Figure 1). At W52, predictors of change in pain remained significant with the exception of SF-36 MCS score (Table 1). Results did not exclude a small number of enrolled pts with fibromyalgia (FM: nGUS=8; nPBO=4). According to these exploratory findings, medical history of FM was associated with lower pain improvement through W24 (p=0.066); in the models run separately in pts with GUS and PBO, pts with FM treated with GUS had a mean (95% CI) pain improvement (-9.1 [-19.5, 1.2]) while pts treated with PBO had a mean worsening (0.7 [-12.5, 13.9]). Pain improvement through 52 wks was significant regardless of FM: pts with FM had a mean (95% CI) improvement of -14.7Table 1.Significant Predictors of Change in Pain (W24 and W52)BL DeterminantW24W52Estimate (95% CL)Estimate (95% CL)Pain score-0.62 (-0.69:-0.55) ‡-0.75 (-0.83:-0.67) ‡Fatigue-0.38 (-0.50:-0.27) ‡-0.37 (-0.53:-0.22) ‡SF-36 MCS0.20 (0.11:0.30)‡0.11 (-0.02:0.24)TJC0.13 (0.06:0.19) †0.12 (0.04:0.21) †NSAID use (Y vs N)2.29 (0.62:3.96) †2.76 (0.55:4.98) ** p <0.05; †p <0.01; ‡p ≤0.0001(-25.9, -3.6) comparable to non-FM pts at W24, while pain improvement in pts with no FM was -22.2 (-24.0, -20.4).ConclusionEarly significant effects of GUS on pain were enhanced through 1 year. Significant predictors of change in pain were consistent at W24 and W52, with the exception of mental health measures. The impact of mental status on pt-reported pain and the potential for GUS to improve pain in pts with FM warrant further consideration.References[1]Gudu T et al. Expert Rev Clin Immunol 2018;14(5):405-17.[2]Nash P et al. ACR Convergence 2021;Nov 5-9 (Poster 21-1368).Disclosure of InterestsPeter Nash Grant/research support from: Janssen, Abbvie, Pfizer, Novartis, Lilly, Gilead, Roche, Sandoz, Celgene, Sun, Boehringer, and Bristol Myers Squibb, Christopher T. Ritchlin Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Grant/research support from: UCB Pharma, AbbVie, Amgen, Proton Rahman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: Janssen and Novartis, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, YoungJa Lee Shareholder of: Johnson & Johnson, Employee of: Janssen Asia Pacific, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Jonathan Sherlock Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Daniel Cua Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Saakshi Khattri Speakers bureau: AbbVie, Eli Lilly, Glenmark, Ichnos Sciences, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Eli Lilly, Glenmark, Ichnos Sciences, Janssen, Novartis, Pfizer, and UCB, Enrique Soriano Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Janssen, Novartis, and Roche, Grant/research support from: AbbVie, Janssen, Novartis, Pfizer, Roche, and UCB, Dennis McGonagle Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB
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Kavanaugh, A., E. Soriano, J. Dutz, C. Selmi, J. Yu, E. Rampakakis, M. Shawi, A. M. Bravo Perdomo, F. Lavie, and L. Coates. "AB1094 GUSELKUMAB EFFECT ON INFLAMMATORY CARDIOVASCULAR (CV) RISK BIOMARKERS, EFFICACY, AND SAFETY IN PSORIATIC ARTHRITIS PATIENTS WITH CV RISK FACTORS: POST-HOC ANALYSIS OF 2 PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDIES." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1770–71. http://dx.doi.org/10.1136/annrheumdis-2023-eular.512.
Full textAbstract:
BackgroundPsA has been associated with an increased risk of cardiovascular disease (CVD), likely due to accelerated atherosclerosis secondary to chronic inflammation.[1]The number of CV risk factors has been shown to correlate with PsA disease activity (DA).[2]ObjectivesDescribe effect of guselkumab (GUS) on inflammatory biomarkers that predict CVD, and its efficacy and safety, in patients (pts) with active PsA and concurrent CV risk factors.MethodsDISCOVER (D)1&2 enrolled adults with active PsA despite standard therapies. D1 pts (31% received 1-2 prior TNF inhibitors [i]), had tender and swollen joint counts (TJC/SJC) each ≥3 and CRP ≥0.3 mg/dL; D2 pts (biologic-naïve) had TJC/SJC each ≥5 and CRP ≥0.6 mg/dL. Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or placebo (PBO)→GUS 100 mg Q4W at W24. Pts included in this analysis had ≥1 of the following CV risk factors: obesity; smoking (past or current); or history of hypertension, diabetes mellitus (DM), or hyperlipidemia. Changes in high-sensitivity (hs) CRP and neutrophil–lymphocyte ratio (NLR) were compared between GUS vs PBO with mixed models adjusting for baseline (BL) levels. Achievement of endpoints at W24 (missing data imputed as no response) was compared in GUS vs PBO with logistic regression adjusting for BL levels, prior TNFi use, and BL DMARD use: American College of Rheumatology (ACR) response criteria, Investigator’s Global Assessment (IGA) of psoriasis score 0/1, DA Index for PsA (DAPSA) low DA (LDA)/remission, PsA DA Score (PASDAS) LDA, minimal DA (MDA), Psoriasis Area and Severity Index (PASI) responses, Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) response, Health Assessment Questionnaire Disability Index (HAQ-DI) response, and enthesitis and dactylitis resolution. The incidence of major adverse CV events (MACE; cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) was assessed through W100.ResultsOf 1120 enrolled pts, 758 had ≥1 CV risk factor (259 Q4W, 252 Q8W, 247 PBO); of these, 448 (59%) were obese, 420 (55%) had hypertension, 315 (42%) were smokers, 171 (23%) had hyperlipidemia, and 103 (14%) had DM. Through W24, GUS significantly reduced hsCRP and NLR vs PBO (Figure 1). Response rates at W24 were significantly higher with GUS vs PBO for all assessed endpoints (Table 1). During the PBO-controlled period, one pt each had a MACE in the PBO (0.9 [95% CI: 0.0-4.9]/100 person-years [PY]) and pooled GUS (0.4; 0.0-2.4)/100PY groups. In the pooled GUS group, the incidence (95% CI) of MACE was 0.2 (0.0-0.8)/100PY over 1 year and 0.3 (0.1-1.0)/100PY over 2 years.ConclusionIn the subgroup of PsA pts with concurrent CV risk factors, GUS was associated with significant reductions in hsCRP and NLR and significantly higher response rates vs PBO for all PsA domains assessed. MACE incidence was similar to that in the overall D1/D2 population.[3]These findings support the efficacy of GUS on systemic inflammation and its cardiovascular safety.References[1]Zheng Z, et al.Front Cardiovasc Med. 2022;9:835439[2]Ferraz-Amaro I, et al.Medicina (Kaunas). 2020;56:415[3]Rahman P, et al.Arthritis Rheumatol.2021;73 (suppl 9)Table 1.Achievement of Efficacy Endpoints at W24 in Pts With Concurrent CV Risk FactorsParameterGUS 100 mg Q4W (N=259)GUS 100 mg Q8W (N=252)PBO (N=247)ACR2062.9%‡58.3%‡30.4%ACR5032%‡28.2%‡11.7%ACR7013.5%†13.1%†4.0%DAPSA LDA (Pts with BL DAPSA >14)39.8%‡40.3%‡19.4%PASI9060.2%‡56.3%‡11.7%PASI10047.5%‡36.5%‡6.5%IGA 0/1 (Pts with BL IGA >1)88.6%‡85.2%‡33.7%Dactylitis resolution (Pts with BL dactylitis)64.8%†62.5%*44.6%Enthesitis resolution (Pts with BL enthesitis)43.7%†48.1%†29.1%FACIT-F Response (Pts with BL FACIT-F ≤48)65.3%‡59.8%†44.1%HAQ-DI Response (Pts with BL HAQ-DI ≥0.35)56.5%‡50.4%‡30.2%MDA23.2%‡20.6%‡7.3%PASDAS LDA (Pts with BL PASDAS >3.2)27.2%‡29.3%‡9.4%*Nominal p<0.05; †p<0.01; ‡p<0.0001 vs PBO.Acknowledgements:NIL.Disclosure of InterestsArthur Kavanaugh Consultant of: AbbVie, Amgen, BMS, Janssen, Eli Lilly, Novartis, Pfizer and UCB, Enrique Soriano Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Roche, and UCB, Consultant of: AbbVie, Janssen, Novartis, and Roche, Grant/research support from: AbbVie, Janssen, Novartis, Pfizer, Roche, and UCB, Jan Dutz Shareholder of: Solius, Speakers bureau: AbbVie, Amgen, Bausch, Eli Lilly, Leo, Janssen, Novartis, Sanofi and Pfizer, Consultant of: Bristol Myers Squib, Grant/research support from: Corbus, Eli Lilly, Carlo Selmi Speakers bureau: AbbVie, Amgen, Alfa-Wassermann, Biogen, Eli-Lilly, Galapagos, Janssen, Novartis, SOBI, Consultant of: AbbVie, Amgen, Alfa-Wassermann, Biogen, Eli-Lilly, Galapagos, Janssen, Novartis, SOBI, Grant/research support from: AbbVie, Amgen, Pfizer, Jenny Yu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Janssen Pharmaceutical Companies of Johnson & Johnson, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, Inc., May Shawi Shareholder of: Johnson & Johnson, Employee of: Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Ana Maria Bravo Perdomo Shareholder of: Johnson & Johnson, Employee of: Immunology Global Medical Affairs, Janssen Latin America, Frederic Lavie Shareholder of: Johnson & Johnson, Employee of: Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Laura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB.
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Curtis, J., I. Mcinnes, P. Rahman, W. Tillett, P. J. Mease, A. Kollmeier, E. C. Hsia, et al. "AB0756 GUSELKUMAB IMPROVED WORK PRODUCTIVITY AND DAILY ACTIVITY IN PATIENTS WITH PSORIATIC ARTHRITIS: RESULTS FROM A PHASE 3 TRIAL." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1675.1–1675. http://dx.doi.org/10.1136/annrheumdis-2020-eular.428.
Full textAbstract:
Background:DISCOVER 2 (DISC 2) is a Phase 3 trial of anti-IL-23-specific mAb guselkumab (GUS) in psoriatic arthritis (PsA) pts, who experience impaired physical function, resulting in disability, work productivity loss, and economic consequences.1Objectives:To evaluate the effect of GUS on impaired work productivity and daily activity in DISC 2 using the Work Productivity and Activity Impairment Questionnaire: Psoriatic Arthritis (WPAI-PsA).Methods:Bio-naïve adults with active PsA despite nonbiologic DMARDs &/or NSAIDs received subcutaneous GUS 100 mg every (q) 4 weeks (W); GUS 100 mg W0, W4, q8W; or placebo (PBO). WPAI-PsA assesses, due to PsA over the previous week, work time missed (absenteeism), impairment while working (presenteeism), and impaired overall work productivity (absenteeism + presenteeism) and daily activity. Percentage change from baseline was analyzed for WPAI-PsA domains using mixed-effect model repeated measure (MMRM). Indirect savings from improved overall work productivity were estimated with 2018 US mean yearly wage estimate (all occupations).2Results:At Week 24, impaired overall work productivity and daily activity were improved 20-22% in GUS-treated and 10-11% in PBO-treated pts (Table). Potential yearly indirect savings from improved overall work productivity was $10,242 with GUS q8W and $10,404 with GUS q4W vs $5,648 with PBO; $4,594 and $4,756 difference, respectively.Conclusion:Improvement in overall work productivity and daily activity was greater with GUS versus PBO among pts with moderate-to-severe PsA, resulting in potential annual incremental economic gains.References:[1]Tillett W et al. Rheumatol (Oxford). 2012;51:275–283.[2]US Bureau of Labor Statistics. May 2018 National Occupational Employment and Wage Estimates United States.https://www.bls.gov/oes/current/oes_nat.htm#00-000Table.Model-based estimates of mean change from baseline in WPAI-PsA domains% change from baselinePBOGUS 100 mg q8WGUS 100 mg q4WW16W24W16W24W16W24Work time missed (absenteeism), n155152141145145143LSMean-4.6 (-7.2,-1.9)-3.5 (-6.4,-0.6)-3.5 (-6.2,-0.7)-3.1 (-6.1,-0.1)-4.7 (-7.4,-2.0)-3.8 (-6.8,-0.8)LSMean diff1.1 (-2.6,-4.8)*0.4 (-3.7,4.5)*-0.2 (-3.9,3.5)*-0.3 (-4.4,3.8)*Impairment while working (presenteeism), n131130125129133130LSMean-10.3 (-13.9,-6.7)-10.2 (-13.7,-6.7)-16.1 (-19.7,-12.4)-19.4 (-22.9,-15.9)-15.1 (-18.7,-11.5)-19.5 (-23.0,-16.0)LSMean diff-5.8 (-10.8,-0.8)†-9.2 (-14.0,-4.4)‡-4.8 (-9.7,0.1)*-9.3 (-14.1,-4.5)‡Overall work productivity impairment (absenteeism + presenteeism), n131130125129133130LSMean-11.2 (-15.0,-7.5)-10.9 (-14.6,-7.1)-15.9 (-19.7,-12.2)-19.7 (-23.4,-16.0)-15.8 (-19.5,-12.1)-20.0 (-23.7,-16.3)LSMean diff-4.7 (-9.9,0.5)*-8.8 (-14.0,-3.7)‡-4.6 (-9.7,0.5)*-9.2 (-14.3,-4.0)‡Daily activity impairment, n244244247246243245LSMean-10.6 (-13.3,-7.9)-10.3 (-13.1,-7.6)-17.1 (-19.8,-14.4)-21.5 (-24.2,-18.7)-17.0 (-19.7,-14.3)-20.5 (-23.2,-17.7)LSMean diff-6.5 (-10.2,-2.8)‡-11.1 (-15.0,-7.4)‡-6.5 (-10.2,-2.7)‡-10.2 (-14.0,-6.4)‡Data are % (95% CI)*p>0.05, †p<0.05,‡p<0.001LSmeans, p values based on MMRMLSmean diffs, p values vs PBOAcknowledgments:NoneDisclosure of Interests:Jeffrey Curtis Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, William Tillett Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer Inc, UCB, Speakers bureau: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer Inc, UCB, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Bei Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Prasheen Agarwal Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Steve Peterson Employee of: Janssen Research & Development, LLC, Chenglong Han Employee of: Janssen Research & Development, LLC
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Braun, J., R. Blanco, H. Marzo-Ortega, L. S. Gensler, F. Van den Bosch, S. Hall, H. Kameda, et al. "POS0299 EFFECT OF SECUKINUMAB ON RADIOGRAPHIC PROGRESSION AND INFLAMMATION IN SACROILIAC JOINTS AND SPINE IN PATIENTS WITH NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS: 2-YEAR IMAGING OUTCOMES FROM A PHASE III RANDOMISED TRIAL." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 397–98. http://dx.doi.org/10.1136/annrheumdis-2022-eular.529.
Full textAbstract:
BackgroundAxial spondyloarthritis (axSpA) is characterised by inflammation of the sacroiliac joints (SIJ) and the spine. Secukinumab (SEC) treatment was clinically efficacious and reduced SIJ bone marrow oedema as detected by magnetic resonance imaging (MRI) in patients (pts) with non-radiographic (nr)-axSpA through 52 weeks in the PREVENT (NCT02696031) study.1ObjectivesTo report radiographic progression and the course of inflammation as assessed by X-ray and MRI of SIJ and spine over 2 years in the PREVENT study.MethodsStudy design and key endpoints have been reported earlier.1 In total, 555 pts were randomised (1:1:1) to receive SEC 150 mg, with (LD) or without loading (NL) doses, or placebo (PBO). Switch to open-label (OL) SEC or standard of care (SoC) was permitted after Week (Wk) 20. All pts (except those who switched to SoC) received OL SEC from Wk 52. Radiographs of the spine and SIJ were collected at baseline (BL) and Wk 104; MR images of the spine and SIJ were collected at BL, Wk 16, 52, and 104. Spinal radiographs were scored using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and SIJ radiographs according to modified New York criteria (mNYC). Pts whose screening SI joint radiographs fulfilled mNY criteria during the eligibility reading session were excluded from the study. Spinal MR images were assessed for signs of inflammation with the Berlin score. SIJ bone marrow oedema was assessed according to the Berlin Active Inflammatory Lesions Scoring. All images were evaluated in blinded fashion independently by 2 central readers. All data are reported from the Wk 104 reading session and are presented as observed.ResultsThe vast majority (98%) of pts treated with SEC 150 mg (pooled LD and NL) showed no structural progression, defined as change in total mSASSS score ≤ smallest detectable change (SDC) of 0.76 (80% agreement level) over 2 years. At BL, 62 pts (43 in SEC, 19 in PBO) presented with ≥1 syndesmophyte (≥1 vertebral unit scored by ≥1 reader). Among these pts, 9 in SEC (20.9%) and 7 in PBO (36.8%) groups had developed ≥1 new syndesmophyte by Wk 104. Among 237 SEC and 117 PBO pts without syndesmophytes at BL, only 4 pts on SEC (1.7%) and 4 pts on PBO (3.4%) developed ≥1 new syndesmophyte by Wk 104. SIJ radiographs showed that 88% of pts on SEC and 86% on PBO had no progression in SIJ (defined as change ≤ SDC (0.46) in total mNYC score) by Wk 104. No patient had an increase in total mNYC score of 2 or more. When screening radiographs of eligible pts were scored alongside post-BL images in the final reading campaign, approximately 25% of pts (68/277 and 34/139 pts in the SEC and PBO groups, respectively) were evaluated as mNY-positive at screening (pts were considered mNY-positive if ≥1 reader evaluated them as mNY-positive). Of these, 11/68 pts in the SEC (16.2%) and 5/34 in the PBO (14.7%) groups were evaluated as mNY-negative at Wk 104. In the SEC and PBO groups, 202 (96.7%) and 102 (97.1%) pts who were mNY-negative at screening stayed negative through Wk 104, respectively. Only 7 pts in the SEC (3.3%) and 3 in the PBO (2.9%) groups who were mNY-negative at BL were scored as mNY-positive at Wk 104. In both groups, fewer pts progressed from mNY-negative to mNY-positive than had a change in the opposite direction (from positive to negative), resulting in an overall negative net progression. Spinal inflammation on MRI (Berlin score) was low at BL with a mean of 0.82 in SEC and 1.07 in PBO groups with no meaningful change up to Wk 104 (mean of 0.56, SEC). SEC reduced SIJ bone marrow oedema score versus PBO at Wk 16 and Wk 52 with sustained reduction through Wk 104 in the overall patient population, with greater reduction in pts with BL score >2 (Figure 1).ConclusionMost pts initially randomised to SEC or PBO showed no radiographic progression through 2 years. There was some discrepancy between SIJ eligibility and efficacy reads. SEC reduced SIJ inflammation (bone marrow oedema) on MRI in pts with active nr-axSpA.References[1]Deodhar A, et al. Arthritis Rheumatol. 2021;73:110–20.Disclosure of InterestsJuergen Braun Speakers bureau: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Medac, MSD (Schering-Plough), Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, UCB pharma, Eli Lilly, Consultant of: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, UCB, Eli Lilly, Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, UCB, Eli Lilly, Ricardo Blanco Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, UCB pharma, MSD, Eli Lilly, Consultant of: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, UCB pharma, MSD, Grant/research support from: AbbVie, MSD, Roche, Helena Marzo-Ortega Speakers bureau: AbbVie, Celgene, Janssen, Eli Lilly and Company, Novartis, Pfizer, Takeda, UCB, Consultant of: AbbVie, Celgene, Janssen, Eli Lilly and Company, Novartis, Pfizer, Takeda, UCB, Grant/research support from: Janssen, Novartis, UCB, Lianne S. Gensler Consultant of: Gilead, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Grant/research support from: UCB, Pfizer, Filip van den Bosch Speakers bureau: AbbVie, BMS, Celgene, Galapagos, Janssen, Eli Lilly, Merck, Novartis, Pfizer, UCB, Consultant of: AbbVie, BMS, Celgene, Galapagos, Janssen, Eli Lilly, Merck, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, BMS, Celgene, Galapagos, Janssen, Eli Lilly, Merck, Novartis, Pfizer, UCB, Stephen Hall Speakers bureau: Novartis, Merck, Janssen, Pfizer, Eli Lilly, UCB, Consultant of: Novartis, Merck, Janssen, Pfizer, Eli Lilly, UCB, Grant/research support from: AbbVie, UCB, Janssen, Merck, Hideto Kameda Speakers bureau: Abbvie, Asahi-Kasei, Astellas, BMS, Chugai, Eisai, Eli Lilly, Gilead Sciences, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer, Consultant of: Abbvie, Astellas, Boehringer, Eli Lilly, Gilead Sciences, Janssen, Novartis, Sanofi, UCB, Grant/research support from: Abbvie, Asahi-Kasei, Boehringer, Chugai, Eisai, Mitsubishi-Tanabe, Denis Poddubnyy Speakers bureau: AbbVie, BMS, Lilly, MSD, Novartis, Pfizer, UCB, Consultant of: AbbVie, Biocad, BMS, Eli Lilly, Gilead, MSD, Novartis, Pfizer, Samsung Bioepis, UCB, Grant/research support from: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, Marleen G.H. van de Sande Speakers bureau: Novartis, MSD, Consultant of: Abbvie, Novartis, Eli Lily, Grant/research support from: Novartis, Eli Lilly, Janssen, UCB, Désirée van der Heijde Paid instructor for: Novartis, AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Pfizer, UCB Pharma, and Director of Imaging Rheumatology BV, Tingting Zhuang Shareholder of: Novartis, Employee of: Novartis, Anna Stefanska Shareholder of: Novartis, Employee of: Novartis, Aimee Readie Shareholder of: Novartis, Employee of: Novartis, Hanno Richards Shareholder of: Novartis, Employee of: Novartis, Atul Deodhar Speakers bureau: AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB
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Rahman, P., P. Helliwell, A. Deodhar, A. Kollmeier, E. C. Hsia, B. Zhou, X. Lin, C. Han, and P. J. Mease. "POS1048 IN PHASE-3 TRIALS DISCOVER 1 & 2, GUSELKUMAB REDUCED FATIGUE OVER 52 WEEKS IN PATIENTS WITH PSORIATIC ARTHRITIS AND DEMONSTRATED INDEPENDENT TREATMENT EFFECTS ON FATIGUE AFTER ADJUSTMENT FOR CLINICAL RESPONSE (ACR20)." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 801.1–801. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1686.
Full textAbstract:
Background:DISCOVER 1 & 2 are phase-3 trials of guselkumab (GUS, an IL-23 inhibitor) in patients with psoriatic arthritis (PsA). In both trials, treatment with GUS led to significantly more improvement than placebo (PBO) in the primary endpoint (American College of Rheumatology 20% improvement criteria [ACR20]) and in other measures of arthritis and psoriasis at week (w) 24,1,2 and these improvements were maintained through 1 year of active treatment.3,4Objectives:To evaluate the effect of GUS on fatigue in DISCOVER 1 & 2 using the patient reported outcome (PRO) FACIT-Fatigue, which has demonstrated content validity and strong psychometric properties in clinical trials.5Methods:DISCOVER 1 & 2 enrolled patients with active PsA, despite non-biologic DMARDS or NSAIDS, who were biologic naïve except ~30% of patients in DISCOVER 1 who had received 1-2 TNFi. Patients were randomized (1:1:1) in a blinded fashion to subcutaneous GUS 100 mg at w0, w4, then every (q) 8w; GUS 100 mg q4w; or matching PBO. At w24, PBO patients were switched to GUS q4w. Concomitant treatment with select non-biologic DMARDS, oral corticosteroids, and NSAIDs was allowed. The FACIT-Fatigue is a 13-item PRO assessing fatigue and its impact on daily activities and function over the past 7 days, total score ranging from 0 to 52, higher score denoting less fatigue. A change of ≥4 points is considered clinically meaningful.5 The change from baseline in FACIT-Fatigue presented below is based on observed data. Mediation analysis6 was applied to the treatment effect of GUS on FACIT-Fatigue to estimate the natural direct and indirect effects, after adjusting for ACR20 response (Table 1).Results:At baseline in DISCOVER 1 & 2, the mean FACIT-fatigue scores (SD) were 30.4 (10.4) and 29.7 (9.7), respectively, indicating that patients with PsA experienced fatigue worse than the general population. At w24 in the DISCOVER trials, treatment with GUS led to significant improvements in FACIT-Fatigue scores compared with PBO, as early as w16 in DISCOVER 1 and w8 in DISCOVER 2. Improvements in fatigue were similar between GUS q4w and q8w doses, and the improvements at w24 were maintained through w52 (Figure 1). After a switch to GUS q4w at w24, PBO patients achieved FACIT-Fatigue scores that were comparable to those of GUS patients (Figure 1). 54%-63% of GUS patients compared with 35%-46% of PBO patients achieved clinically meaningful improvement (≥4 points) in FACIT-Fatigue at w24 (P≤0.003). At w52, 61%-70% of both GUS and PBO to GUS groups reached this improvement. As evaluated by mediation analysis at w24, GUS had independent positive treatment effects on fatigue (12%-36% in the q8w GUS dosing group and 69%-70% in the q4w GUS group) after adjustment for ACR20 response (Table 1).Conclusion:In 2 phase-3 trials, GUS treatment improved fatigue when compared to PBO during PBO-controlled periods and maintained improvements through 1 year of active treatment. Substantial proportions of those effects were independent of the effects on ACR20, especially for the q4W dosing group.References:[1]Deodhar et al. Lancet 2020;395:1115[2]Mease et al. Lancet 2020;395:1126[3]Ritchlin et al. EULAR20. SAT0397[4]McInnes et al. EULAR20. SAT0402[5]Cella et al. J Patient-Reported Outcomes 2019;3:30[6]Valeri et al. Psychologic Meth 2013;18:137Table 1.Mediation Analysis: Guselkumab Has Direct Effects and Indirect Effects (Mediated through ACR20) on Fatigue in PsAEffectGUS 100 mg q8w vs. PBO (95% CI)GUS 100 mg q4w vs. PBO (95% CI)DISCOVER-1Total Effect3.1 (1.0, 5.2)(p<0.02)3.8 (1.9, 5.4)(p<0.02)% Direct Effect11.7%68.5%% Indirect effect mediated by ACR2088.3%31.5%DISCOVER-2Total Effect4.0 (2.4, 5.5)(p<0.02)3.6 (2.1, 5.0)(p<0.02)% Direct Effect36.3%69.7%% Indirect effect mediated by ACR2063.7%30.3%ACR, American College of Rheumatology; CI, confidence interval; GUS, guselkumab; PBO, placebo; PsA, psoriatic arthritis; q4W, every 4 weeks; q8W, every 8 weeksDisclosure of Interests:Proton Rahman Speakers bureau: Received speakers fees from Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Grant/research support from: Received grant/research support from Janssen and Novartis, consultation fees from Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer, Philip Helliwell Consultant of: Consultation fees paid to charity (AbbVie, Amgen, Pfizer, UCB) or himself (Celgene, Galapagos), Grant/research support from: Received grants/research support paid to charity (AbbVie, Janssen, Novartis), Atul Deodhar Speakers bureau: Received speakers fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Consultant of: Received consultation fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Grant/research support from: Received grant/research support from AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Alexa Kollmeier Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Bei Zhou Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Xiwu Lin Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Chenglong Han Shareholder of: Shareholder of Johnson & Johnson, Employee of: Employee of Janssen Research & Development, LLC, Philip J Mease Speakers bureau: Received speakers fees from Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB, Consultant of: Received consultation fees from Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB, Grant/research support from: Received grant/research support from Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB.
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Ogdie, A., J. F. Merola, P. J. Mease, C. T. Ritchlin, J. U. Scher, D. Chan, S. D. Chakravarty, et al. "AB0887 Designing a Phase 3b, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Investigate the Effect of Guselkumab Dosing Interval in Psoriatic Arthritis Patients with Inadequate Response to Tumor Necrosis Factor Inhibition." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 1567.2–1568. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1318.
Full textAbstract:
BackgroundTumor necrosis factor inhibitors (TNFi) are frequently chosen as the first biologic therapy for patients (pts) with psoriatic arthritis (PsA), though a sizeable proportion of pts have an inadequate response (IR), and some may also have intolerance. Guselkumab (GUS), a human mAb that targets the IL-23 p19 subunit, provides an alternative mechanism of action to treat PsA. In the Phase 3 (Ph3) DISCOVER-1 study of GUS in active PsA, GUS every 4 weeks (Q4W) and Q8W clinical response rates were generally consistent between TNFi-naïve (263 pts) and TNFi-experienced (118 pts) cohorts. In the TNFi-experienced cohort and the limited number of DISCOVER-1 pts with IR to their prior TNFi (N=44), American College of Rheumatology 50% improvement (ACR50) and ACR70 response rates at W24 were numerically higher in GUS Q4W- than Q8W-treated pts.1ObjectivesTo further investigate whether GUS Q4W could provide incremental benefit to some TNFi-IR PsA pts by analyzing the existing DISCOVER-1 dataset to facilitate the design of a new clinical trial.MethodsStudy feasibility assessments included comparison of key efficacy endpoints by treatment group at W24 among TNFi-experienced pts receiving GUS Q8W and Q4W in DISCOVER-1. Results from the DISCOVER-1 study also informed sample size power calculations for a primary endpoint of ACR20 response at W24 in a future study in a TNFi-IR PsA pt population.ResultsComparison of several efficacy endpoints (ACR70 response, minimal disease activity, Investigator’s Global Assessment [IGA] of psoriasis 0/1 response) across treatment groups in the TNFi-experienced DISCOVER-1 cohort supports a potential dose response, with more frequent GUS administration eliciting numerically higher response rates (Table 1). A similar trend was observed for ACR20/50/70 responses in the smaller TNFi-IR population1, though these findings should be interpreted with caution due to limited sample size. ACR20 response rates at W24 of DISCOVER-1 were employed to estimate sample size requirements for a new study. Assuming comparable rates of GUS treatment effect seen in DISCOVER-1, a sample size of 150 randomized pts per group for PBO, GUS Q8W, and GUS Q4W would provide >90% power to detect a significant difference between each GUS group and PBO for ACR20 response at W24. Based on these findings, a new Ph3b, multicenter, randomized, double-blind, PBO-controlled study, SOLSTICE, was designed to further evaluate the efficacy and safety of GUS in approximately 450 pts with active PsA who had IR to one prior TNFi, and to investigate the effect of GUS dosing interval in this important cohort of pts with PsA (Figure 1).Table 1.Clinical efficacy at W24 among DISCOVER-1 TNFi-experienced ptsPlaceboGUS Q8WGUS Q4WACR2017.9% (7/39)56.1% (23/41)57.9% (22/38)ACR505.1% (2/39)26.8% (11/41)34.2% (13/38)ACR702.6% (1/39)2.4% (1/41)21.1% (8/38)MDA2.6% (1/39)17.1% (7/41)26.3% (10/38)IGA 0/1a7.7% (2/26)48.3% (14/29)67.9% (19/28)aIGA score of 0 (clear) or 1 (almost clear) among pts with ≥3% body surface area of psoriatic involvement and an IGA score ≥2 (mild-to-severe psoriasis) at baseline.ACR20/50/70, American College of Rheumatology 20%/50%/70% improvement; GUS, guselkumab; IGA, Investigator’s Global Assessment; MDA, minimal disease activity; Q4W, every 4 weeks; Q8W, every 8 weeks; TNFi, tumor necrosis factor inhibitor; W, weekConclusionPsA pts with TNFi-IR are typically difficult to treat. Overall data from the pivotal DISCOVER-1 study of GUS in pts with active PsA showed consistent clinical response between doses and between TNFi-naïve and TNFi-experienced pts. Analyses based on limited numbers of TNFi-experienced pts from DISCOVER-1 demonstrated potential incremental benefit for achievement of higher response criteria with more frequent dosing in some TNFi-IR pts. SOLSTICE, a Ph3b, randomized, placebo-controlled study, will test this hypothesis.References[1]Deodhar A, et al. Lancet. 2020;395:1115-1125.Figure 1.Disclosure of InterestsAlexis Ogdie Shareholder of: Her husband has received royalties from Novartis, Consultant of: AbbVie, Amgen, BMS, Celgene, Corrona, Gilead, Global Health Living Foundation, Janssen, Eli Lilly, Novartis, Pfizer, and UCB Pharma, Grant/research support from: Abbvie, Pfizer and Novartis/Amgen to the University of Pennsylvania, Joseph F. Merola Paid instructor for: AbbVie, Arena, Biogen, Bristol Myers Squibb, Dermavant, Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma, Consultant of: AbbVie, Arena, Biogen, Bristol Myers Squibb, Dermavant, Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma, Philip J Mease Speakers bureau: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Aclaris, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Christopher T. Ritchlin Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, and Janssen, Grant/research support from: UCB Pharma, AbbVie, and Amgen, Jose U. Scher Consultant of: Janssen, Novartis, Pfizer, Abbvie, Sanofi, Kaleido and UCB Pharma, Grant/research support from: Novartis, Pfizer and Janssen (for investigator-initiated studies), Daphne Chan Employee of: Janssen Scientific Affairs, LLC, and may own stock or stock options in Johnson & Johnson, Soumya D Chakravarty Employee of: Janssen Scientific Affairs, LLC, and may own stock or stock options in Johnson & Johnson, Wayne Langholff Employee of: Janssen Research & Development, LLC, and may own stock or stock options in Johnson & Johnson, Olivia Choi Employee of: Janssen Scientific Affairs, LLC, and may own stock or stock options in Johnson & Johnson, Yevgeniy Krol Employee of: Janssen Scientific Affairs, LLC, and may own stock or stock options in Johnson & Johnson, Katelyn Rowland Employee of: Janssen Scientific Affairs, LLC, and may own stock or stock options in Johnson & Johnson, Alice B Gottlieb Consultant of: AnaptsysBio, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol-Myers Squibb Co., Incyte, GSK, Janssen, LEO Pharma, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical Industries, Inc., UCB Pharma, Dermavant, and Xbiotech, Grant/research support from: Boehringer Ingelheim, Incyte, Janssen, Novartis, UCB Pharma, Xbiotech, and Sun Pharma
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Köhm, M., T. Rossmanith, A. C. Foldenauer, H. Kellner, U. Kiltz, J. Rech, G. R. Burmester, et al. "POS1059 EFFICACY OF UST IN ACTIVE PsA IS INDEPENDENT FROM CONCOMITANT MTX USE, EVEN IN PATIENTS WITH MORE SEVERE SKIN PSORIASIS: SUBGROUP ANALYSIS FROM A RANDOMIZED PLACEBO-CONTROLLED INVESTIGATOR INITIATED CLINICAL TRIAL." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 850.2–851. http://dx.doi.org/10.1136/annrheumdis-2022-eular.3929.
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BackgroundThe use of bDMARDs treatments in patients with psoriatic arthritis (PsA) usually requires treatment failure or intolerance of csDMARD/MTX before initiation. The value of MTX in combination with bDMARDs is still unclear. We designed an investigator-initiated, randomized, placebo-controlled trial (IIT) in active PsA to examine if outcomes of treatment with ustekinumab (UST) in combination with MTX (either newly initiated or ongoing) were different from UST only (+Placebo; PBO). With known efficacy of MTX on skin psoriasis outcomes may differ in patients with or without significant skin involvement of their psoriatic disease.ObjectivesTo compare efficacy outcomes in UST+PBO vs UST+MTX in dependency of skin involvement (Body Surface Area [BSA]) at baseline.MethodsA total of 186 patients with active PsA (defined as TJC≥4, SJC≥4 [68/66 joint count] and DAS28≥3.2) were screened for eligibility. 173 patients were randomized to UST+MTX (new or ongoing) or UST+PBO.With this post hoc subgroup analysis outcome parameters were compared between patients with or without skin psoriasis > 3 % BSA. Demographic data and disease activity status of arthritis (joint count [TJC/SJC], DAPSA, DAS28), skin (PASI, BSA), HR-QoL (EQ5D, DLQI) and physical function (HAQ) were compared between groups.ResultsBL data were well-balanced between main treatment groups (UST+MTX, n=86; UST+PBO, n=74) including gender (42.5% vs 40.5% female) and mean values for age (49.2 vs 47.2 years), BMI (29.4 vs 28.9 kg/m2), SJC (8 vs 8), TJC (12 vs 12), DAS28-CRP (4.6 vs 4.4), DAPSA (36.7 vs 34.9) and PASI (2.8 vs 2.4. Disease activity remained well-balanced even after dividing groups according to skin involvement ((a) BSA ≤3% and (b) BSA >3%) with a trend of more severe joint involvement (SJC, TJC) in BSA >3% for UST+MTX compared to UST+PBO. At week 24, relative changes in TJC (-62% vs -62%), change in DAS28 and DAPSA were equal in all treatment groups independent from skin involvement (Table 1). Differences between the groups according to skin involvement were seen for relative changes in SJC (BSA >3%: -74.8% UST+MTX vs -84.3% UST+PBO), subject global assessment (SGA), physician global assessment (PGA), DLQI and EQ5D. Highest levels for changes were detected in the UST+PBO group with high skin involvement (BSA >3%).Table 1.Outcomes at Week 24 (LOCF)UST+MTXUST+PBOBSA ≤3%BSA >3%BSA ≤3%BSA >3%n=46n=40n=51n=23TJC68 change from BL-7.83 (SD 10.3)-9.5 (SD 10.3)-8.9 (SD 9.5)-7.3 (SD 7.4)SJC66 change from BL-6.0 (SD 5.4)-7.1 (SD 3.5)-6.5 (SD 6.2)-6.4 (SD 3.8)PASI change from BL+-1.3 (SD 1.9)-8.5 (SD 9.6)-1.5 (SD 2.4)-9.0 (SD 10.7)DAS-28 ESR [mm/hr] change from BL-1.6 (SD 1.1)-1.8 (SD 1.2)-1.7 (SD 1.4)-1.8 (SD 1.1)DAS-28 CRP [mg/l] change to BL-1.5 (SD 1.2)-1.5 (SD 1.3)-1.6 (SD 1.2)- 1.7 (SD 1.1)DAPSA change from BL-17.4 (SD 16.8)-20.8 (SD 13.2)-20.5 (SD 16.6)-20.4 (SD 15.3)HAQ change from BL-0.1 (SD 0.4)-0.2 (SD 0.5)-0.3 (SD 0.3)-0.3 (SD 0.5)DLQI change from BL-3.1 (SD 5.5)-5.5 (SD 8.2)-2.3 (SD 3.3)-6.4 (SD 7.9)EQ5D VAS Health State change from BL6.7 (SD 24.7)11.7 (SD 23.6)8.0 (SD 24.2)21.3 (SD 25.3)ConclusionIL12/23 inhibition with UST is an effective treatment for active PsA independent of MTX use. Data from this IIT indicate that additional MTX has no positive impact on UST efficacy for arthritis, skin, HR-QoL and physical function. This independency of UST effect from MTX can also be demonstrated in patients with active skin involvement despite known efficacy of MTX for skin psoriasis.AcknowledgementsWe thank Janssen for support of the study with a research grant.Disclosure of InterestsMichaela Köhm Speakers bureau: Janssen, Consultant of: Janssen, Grant/research support from: Janssen, Tanja Rossmanith Grant/research support from: Janssen, Ann Christina Foldenauer Grant/research support from: Janssen, Herbert Kellner Speakers bureau: Janssen, Consultant of: Janssen, Uta Kiltz Speakers bureau: Abbvie, Fresenius, Hexal, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: AbbVie, Amgen, Biocad, Biogen, Chugai, Eli Lilly, Hexal, Grünenthal, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Grant/research support from: AbbVie, Amgen, Biogen, Fresenius, GSK, Hexal, Novartis, Pfizer, Jürgen Rech Speakers bureau: Abbvie, Biogen, BMS, Chugai, GSK, Lilly, MSD; Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: Biogen, BMS, Chugai, GSK, Lilly, MSD, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Novartis, Sobi, Gerd Rüdiger Burmester Speakers bureau: Janssen, Consultant of: Janssen, Grant/research support from: Janssen, David M Kofler Speakers bureau: Janssen, Consultant of: Janssen, Grant/research support from: Janssen, Jan Brandt-Juergens Speakers bureau: Janssen, Consultant of: Janssen, Grant/research support from: Janssen, Christin Jonetzko Grant/research support from: Janssen, Harald Burkhardt Speakers bureau: Janssen, Consultant of: Janssen, Grant/research support from: Janssen, Frank Behrens Speakers bureau: Janssen, Consultant of: Janssen, Grant/research support from: Janssen
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O’ Brien, A., M. Hanlon, V. Marzaioli, K. Flynn, S. Wade, D. Veale, and U. Fearon. "POS0411 TARGETING JAK-STAT SIGNALLING ALTERS THE PHENOTYPIC CHARACTERISTICS OF PsA SYNOVIAL FIBROBLASTS IN RESPONSE TO THE JAK/STAT ACTIVATOR ONCOSTATIN M." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 435.1–435. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2528.
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Background:Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis. The JAK/STAT pathway has been linked to the pathogenesis of PsA. Recently, JAK/STAT inhibitors (JAKi) have emerged as an encouraging class of drugs for the treatment of PsA. Only a few of these inhibitors have been approved for use in PsA patients with others currently in clinical trials.Objectives:The aim of this study was to examine the effect of JAKi on primary PsA synovial fibroblasts (FLS) function.Methods:Primary PsA FLS were isolated and cultured with JAKi (Peficitinib, Filgotinib, Baricitinib and Upadacitinib) in the presence of the pro-inflammatory JAK/STAT activator - Oncostatin M (OSM). The effect of JAKi on these cells was determined by Migration and Invasion Assays, ELISA and rtPCR. PsA FLS bioenergetics was assessed using an XF24 analyser, which simultaneously quantifies two energetic pathways- glycolysis (ECAR) and Oxidative phosphorylation (OCR).Results:OSM-induced Migration and Invasion was supressed by all JAKi with Peficitinib, Filgotinib and Baracitinib showing the greatest effect. Analysis by ELISA and rtPCR showed reduction in MCP-1 and IL-6 expression in response to JAKi, in contrast, an increase in IL-8 was observed. These functional effects were accompanied by a change in the cellular bioenergetic profile of PsA FLS, where OSM significantly increased the ECAR:OCR ratio in favour of glycolysis where PsA FLS displayed a hypermetabolic phenotype. This effect was reversed in the presence of JAKi, which specifically targeted the glycolytic pathway with PsA FLS returning to a more quiescent phenotype.Conclusion:This study demonstrates that JAK/STAT signalling mediates the complex interplay between inflammation and cellular metabolism in PsA pathogenesis, inhibition of which shows effective suppression of the pathogenic phenotype of PsA FLS that drives joint destruction.References:[1]Chen M, Dai SM. A novel treatment for psoriatic arthritis: Janus kinase inhibitors. Chin Med J (Engl). 2020;133(8):959-967.Disclosure of Interests:Aisling O’ Brien: None declared, Megan Hanlon: None declared, Viviana Marzaioli: None declared, Keelin Flynn: None declared, Siobhan Wade: None declared, Douglas Veale Speakers bureau: Abbvie, Janssen, Novartis, MSD, Pfizer, UCB, Consultant of: Abbvie, Janssen, Novartis, MSD, Pfizer, UCB, Grant/research support from: Janssen, Abbvie, Pfizer, UCB, Ursula Fearon Speakers bureau: Abbvie, Grant/research support from: Janssen, Abbvie, Pfizer, UCB
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Sparfel, M. A., S. Derolez, J. Law-Wan, N. Azzopardi, P. Goupille, D. Mulleman, and T. Bejan-Angoulvant. "POS0636 INFLUENCE OF DEMOGRAPHIC AND DISEASE RELATED FACTORS ON EFFICACY OF INFLIXIMAB OR GOLIMUMAB IN RHEUMATOID ARTHRITIS. A META-ANALYSIS ON RANDOMIZED PLACEBO- CONTROLLED TRIALS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 556.1–556. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3565.
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Background:TNF inhibitors have changed the course of rheumatoid arthritis (RA). Yet, detailed analysis on factors influencing clinical response to TNF inhibitors in RA is lacking.Objectives:Herein we aimed at studying the impact of demographics and disease-related factors on therapeutic response to golimumab and infliximab in RA.Methods:Randomized clinical trials (RCTs) that evaluated golimumab and infliximab versus placebo or conventional therapy were sought. We selected the following factors: age, sex, ethnicity, body mass index (BMI), smoking status, physical activity, disease duration, disease activity at baseline, presence of auto-antibodies. We studied the impact of these factors on clinical response using firstly aggregate data in a Mantel-Haenszel random effects model, and secondly individual data in a multivariate regression model.Results:Individual data from 8 RCTs, 2 on infliximab (n=1477) and 6 on golimumab (total =3041) were obtained. In the aggregate model analysis, none of the selected factors had a significant impact on clinical response. In the multivariate analysis, male sex and physical activity were significantly associated with a lower DAS28-CRP after 6 months of treatment (regression coefficients -0.264 (p<0.001) and -0.193 (p=0.004) respectively), while a high initial DAS28-CRP was significantly associated with a higher DAS28-CRP (regression coefficient 0.579 (p<0.001)). The baseline disease activity was the only significant interaction factor with the effect of the treatment.Conclusion:Male gender and practicing physical activity are associated with lower disease activity 6 months after golimumab or infliximab initiation. High baseline disease activity significantly influences negatively the effect of the treatment on disease activity score.Acknowledgements:This study, carried out under YODA Project 2018-2931, used data obtained from the Yale University Open Data Access Project, which has an agreement with JANSSEN RESEARCH & DEVELOPMENT, L.L.C. The interpretation and reporting of research using this data are solely the responsibility of the authors and does not necessarily represent the official views of the Yale University Open Data Access Project or JANSSEN RESEARCH & DEVELOPMENT, L.L.C.Disclosure of Interests:Marc-Antoine SPARFEL: None declared, Sophie Derolez: None declared, Johan Law-Wan: None declared, Nicolas Azzopardi: None declared, Philippe Goupille Speakers bureau: Abbvie, Biogaran, BMS, Hospira, Janssen, MSD, Pfizer, Sanofi-Genzyme, UCB, Consultant of: Abbvie, Biogaran, BMS, Hospira, Janssen, MSD, Pfizer, Sanofi-Genzyme, UCB, Grant/research support from: Clinical trials sponsored by Abbvie, Roche, BMS, Boehringer, Lilly, Novartis, Pfizer, UCB, Janssen and MSD. Invitation to an international congresses by MSD, Roche, BMS and Abbvie, Denis Mulleman Speakers bureau: Pfizer and Novartis, Consultant of: Pfizer and Novartis, Grant/research support from: Invitation to an international congress by Janssen-Cilag, Theodora Bejan-Angoulvant: None declared
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Nash, P., L. S. Tam, W. C. Tsai, Y. Y. Leung, D. Furtner, S. Sheng, Y. Wang, et al. "POS1044 GUSELKUMAB PROVIDES CONSISTENT AND DURABLE PAIN IMPROVEMENT IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS: RESULTS OF 2 PHASE 3, RANDOMIZED, CONTROLLED CLINICAL TRIALS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 839–40. http://dx.doi.org/10.1136/annrheumdis-2022-eular.2030.
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BackgroundGuselkumab (GUS), an anti-IL23p19-subunit mAb, demonstrated significant efficacy vs placebo (PBO) in achieving ACR20 response at week (W) 24 in patients (pts) with active PsA in phase 3 trials, DISCOVER-1&2 (D1&2).1,2 Pts with PsA report pain relief as a treatment priority.3ObjectivesTo assess GUS treatment effect through 2 years on pt-reported pain across outcome measures.MethodsPts with active PsA in D1 (n=381; 31% received 1-2 prior TNFi) and D2 (n=739; biologic-naïve) were randomized (1:1:1) to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or PBO with crossover to GUS 100 mg Q4W at W24 (PBO→Q4W). Pts rated pain using visual analog scale (VAS; 0-10; Pt Pain) and reported Bodily Pain intensity over past 4 W via 36-Item Short-Form Health Survey question 21 (0-5). Pts with spondylitis and peripheral arthritis at baseline (BL) rated Spinal and Joint Pain (0-10). Observed mean change, % improvement from BL in tender (TJC; 0-68) and swollen joint counts (SJC; 0-66), and proportion of pts achieving ≥20/≥50% improvement in Pt Pain (nonresponder imputation [NRI]) were evaluated.ResultsIn D2, mean BL for Bodily Pain (range: 4.4-4.5), Pt Pain (6.2-6.3), Spinal Pain (6.5-6.7), Joint Pain (6.3-6.8), SJC (11.7-12.9) and TJC (19.8-22.4) indicated moderate pain and disease activity at study outset. GUS-treated pts reported ~2x improvement in Pt Pain, Spinal Pain, Joint Pain, and Bodily Pain intensity at W24 vs PBO, which were maintained or increased at W52 and W100. PBO→Q4W pts had similar improvements. Pt-reported pain appeared more sensitive to treatment effect, with larger differences in % improvement vs PBO than physician-reported TJC/SJC at W24. D1 showed consistent results through 1 year. In 748 GUS-treated pts across D1&2, substantial proportions achieved meaningful improvement in Pt Pain at early time points: 32% (W4) and 48% (W8) achieved ≥20% improvement; 28% (W12) and 33% (W16) achieved ≥50% improvement. At W24, 63%/39% reported ≥20%/≥50% improvement in pain.ConclusionGUS provided consistent and durable improvements in pt-reported pain across several outcome measures. Pt-reported pain as an early and sensitive indicator of treatment effect in pts with active PsA and additional factors merits further evaluation.References[1]Deodhar A et al. Lancet. 2020;395:1115-25[2]Mease P et al. Lancet. 2020;395:1126-36[3]Gudu T et al. Expert Rev Clin Immunol. 2018;14:405-17Table 1.Observed Mean (SD) Change from Baseline in Pain Scores, TJC, and SJC at W24, W52, and W100 in DISCOVER-2W24W52W100GUS Q4WGUS Q8WPBOGUS Q4WGUS Q8WPBO→Q4WGUS Q4WGUS Q8WPBO→Q4WPt Pain (0-10),* N240243243229234231220224215-2.39 (2.35)-2.53 (2.47)-1.08 (2.42)-2.89 (2.68)-3.20 (2.56)-2.75 (2.66)-3.52 (2.62)-3.69 (2.63)-3.41 (2.58)Spinal Pain (0-10), +N806592796488766182-2.26 (2.57)-2.54 (2.70)-1.13 (2.48)-2.74 (2.63)-2.67 (2.71)-2.65 (2.69)-3.11 (2.67)-3.44 (2.71)-3.37 (2.66)Joint Pain (0-10),+N806592796488766182-2.88 (2.17)-2.90 (2.68)-1.40 (2.91)-3.32 (2.27)-3.21 (2.76)-3.42 (2.92)-3.54 (2.35)-3.61 (2.77)-3.80 (2.95)SF-36 (Q21; 0-5), N240243242229234230220224214-0.99 (1.03)-1.03 (1.12)-0.50 (1.11)-1.18 (1.33)-1.29 (1.17)-1.10 (1.16)-1.39 (1.25)-1.47 (1.38)-1.36 (1.27)TJC (0-68), N240243243228234231220224213-11.85(9.88)-10.37(9.49)-7.26(11.15)-15.04(10.51)-13.44(10.03)-14.15(11.39)-16.37(10.70)-15.27(11.10)-16.29(11.27)SJC (0-66), N240243243228234231220224213-8.77(5.46)-8.14(6.07)-6.44(7.20)-10.38(6.17)-9.56(6.28)-10.17(6.79)-10.83(6.66)-10.20(6.88)-10.58(6.15)*ACR, DAPSA, MDA: VAS 0-10; +BASDAI: VAS 0-10ACR=American College of Rheumatology; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; DAPSA=Disease Activity in Psoriatic Arthritis; GUS=guselkumab; MDA=minimal disease activity; PBO=placebo; pt=patient; Q=question; QxW=every x week; SD=standard deviation; SF-36=36-Item Short-Form Survey; SJC=swollen joint count; TJC=tender joint count; VAS=visual analog scale; W=weekDisclosure of InterestsPeter Nash Consultant of: AbbVie, Bristol Myers Squibb, Boehringer, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Roche, Sandoz, and Sun Pharma, Grant/research support from: AbbVie, Bristol Myers Squibb, Boehringer, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Roche, Sandoz, and Sun Pharma, Lai-Shan Tam Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly, Janssen, Pfizer, and Sanofi, Grant/research support from: Amgen, Boehringer Ingelheim, GSK, Janssen, Novartis, and Pfizer, Wen-Chan Tsai Consultant of: AbbVie, Eli Lilly, Novartis, Pfizer, and Janssen, Ying Ying Leung Consultant of: AbbVie, Eli Lilly, Janssen, and Novartis and on advisory board for Janssen, Daniel Furtner Shareholder of: Johnson & Johnson, Employee of: Janssen, a division of Johnson & Johnson Pte. Ltd, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research and Development, LLC, Yanli Wang Consultant of: Janssen, Employee of: Cytel, Inc., May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research and Development, LLC, Jonathan Sherlock Shareholder of: Johnson & Johnson, Employee of: Janssen Research and Development, LLC, Daniel Cua Shareholder of: Johnson & Johnson, Employee of: Janssen Research and Development, LLC
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Baraliakos, X., D. D. Gladman, S. D. Chakravarty, C. Gong, M. Shawi, E. Rampakakis, M. Kishimoto, E. Soriano, and P. J. Mease. "POS0023 PERFORMANCE OF BASDAI VS. ASDAS IN EVALUATING AXIAL INVOLVEMENT IN PATIENTS WITH PSA TREATED WITH GUSELKUMAB: POOLED ANALYSIS OF TWO PHASE 3 STUDIES." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 217.2–218. http://dx.doi.org/10.1136/annrheumdis-2023-eular.2761.
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BackgroundAlthough the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is used to assess the activity of axial disease in patients (pts) with psoriatic arthritis (PsA), only one of its questions is specific to axial symptoms. Alternatively, the Ankylosing Spondylitis Disease Activity Score (ASDAS) excludes assessment of enthesitis, gives less weight to peripheral activity and is considered more objective than the BASDAI.ObjectivesThe current post hoc analysis aimed to compare the performance of BASDAI and ASDAS in evaluating symptoms of axial involvement in pts with axial PsA (axPsA).MethodsPts enrolled in the DISCOVER-1 (D1) and DISCOVER-2 (D2) studies were adults with active PsA despite standard therapies. D1 pts had ≥3 swollen and ≥3 tender joints (SJC; TJC) and C-reactive protein (CRP) ≥0.3 mg/dL; D2 pts had SJC ≥5, TJC ≥5 and CRP ≥0.6 mg/dL. 31% of D1 pts received 1-2 prior tumor necrosis factor inhibitors; D2 pts were biologic-naïve. Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or placebo with crossover to GUS Q4W at W24. axPsA was defined by presence of sacroiliitis based on previous radiograph or magnetic resonance (MR) imaging confirmation. Data were pooled across all treatment groups. In addition to BASDAI and ASDAS, modified versions excluding the peripheral arthritis and enthesitis questions (mBASDAI) and the peripheral arthritis question (mASDAS) were calculated. Normalized (scale of 0-10) versions of ASDAS and mASDAS were calculated based on maximum scores of ≈7 and ≈6.3, respectively. The correlation of BASDAI/mBASDAI and ASDAS/mASDAS with SJC, TJC, enthesitis, Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue, pt pain, pt global, and physician global was assessed with Pearson’s correlation coefficient. The cross-sectional and longitudinal (W52) effects of Leeds enthesitis index (LEI), SJC, and axPsA on BASDAI/mBASDAI and ASDAS/mASDAS were assessed with mixed models.Results436 pts with available baseline (BL) BASDAI information were included in the analysis. In pts with axPsA, BASDAI showed weak correlation with SJC, TJC, LEI, and physician global; moderate correlation with fatigue; and strong correlation with pt global and pt pain. Similar results were observed for ASDAS and modified versions. Among pts without axPsA, correlations of BASDAI and ASDAS with SJC, TJC, and LEI remained weak; correlations with pt global and pt pain remained strong. Longitudinally, among pts with and without BL enthesitis, respectively, LEI and SJC showed significant but not clinically important associations with either outcome. Presence of axial disease was associated with significantly greater BASDAI and ASDAS scores, at BL and longitudinally, without differences in the incremental effect on BASDAI, normalized ASDAS, or their modified versions.ConclusionIn pts with axPsA, the BASDAI and ASDAS performed similarly, with both demonstrating weak correlations with peripheral arthritis and moderate/strong correlations with pt fatigue and pain. The BASDAI and ASDAS also showed similar ability to discern changes in axial disease activity. These results suggest that both BASDAI and ASDAS are valid, and perform comparably, in assessing activity of axial disease in PsA pts.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsXenofon Baraliakos Consultant of: AbbVie, Chugai, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, MSD, and Novartis, Dafna D Gladman Consultant of: BMS, Galapagos, Gilead, and Novartis, Grant/research support from: AbbVie, Amgen, Eli Lilly, Janssen, Pfizer, UCB, Soumya D Chakravarty Employee of: Janssen Scientific Affairs, LLC and shareholder in Johnson & Johnson, of which Janssen Scientific Affairs, LLC is a wholly-owned subsidiary, Cinty Gong Employee of: Janssen Scientific Affairs, LLC and shareholder in Johnson & Johnson, of which Janssen Scientific Affairs, LLC is a wholly-owned subsidiary, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies, a wholly-owned subsidiary of Johnson & Johnson, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, Mitsumasa Kishimoto Speakers bureau: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Tanabe-Mitsubishi, and UCB Pharma, Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Tanabe-Mitsubishi, and UCB Pharma, Enrique Soriano Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Janssen, Novartis, and Roche, Grant/research support from: AbbVie, Janssen, Novartis, Pfizer, Roche, and UCB, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB.
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Merola, J. F., Y. H. Liu, Y. W. Yang, M. Miller, M. Shawi, D. Chan, S. Khattri, L. Savage, W. H. Boehncke, and C. Han. "AB0893 An Analysis of Fatigue in Patients With Psoriatic Disease Utilizing SF-36 Vitality Scores: Results Through Week 24 in Phase 3 Trials of Guselkumab in Patients With Psoriasis and Psoriatic Arthritis." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 1573–74. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1514.
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BackgroundPatients with chronic inflammatory diseases can experience significant fatigue, negatively impacting health-related quality-of-life.1,2ObjectivesThis post-hoc analysis evaluated baseline fatigue severity among patients with psoriasis and/or psoriatic arthritis (PsA) and the effect of guselkumab treatment on patient-reported fatigue.MethodsVOYAGE-2 evaluated guselkumab every 8 weeks (Q8W) versus placebo (W16→guselkumab) and adalimumab in treating moderate-to-severe psoriasis.3 DISCOVER-14 and DISCOVER-25 evaluated guselkumab Q4W and Q8W versus placebo in treating active PsA. Fatigue was assessed using 36-item Short Form (SF-36) vitality scale score (includes 4 questions on fatigue/energy level); the US population norm=50±10; 5-10-point decrements are typically observed in conditions known to cause fatigue2; scores ≤35 indicate clinically important fatigue1; increases ≥5 indicate clinically meaningful improvement.2ResultsAcross randomized groups at baseline, mean SF-36 vitality scores were 47.7-48.5 in psoriasis and 42.2-44.0 in PsA patients; 11%-15% of psoriasis and 20%-28% of PsA patients had scores <35. In psoriasis patients, mean increases in SF-36 vitality score at W16 were: placebo, 1.1; adalimumab, 3.9 (p<0.001 versus placebo); guselkumab, 5.6 (p<0.001 versus placebo); at W24: placebo→guselkumab, 4.6; adalimumab, 3.9; guselkumab, 5.8 (p=0.0148 versus adalimumab). In PsA patients, mean increases at W24 were: placebo, 2.3-4.0; guselkumab, 5.5-7.5 (p≤0.001 versus placebo). Through the placebo-controlled periods, significantly greater proportions of guselkumab-treated patients achieved clinically meaningful improvement in fatigue versus placebo (W16 psoriasis: guselkumab, 48%; placebo, 32%; p<0.001; W24 PsA: guselkumab, 53%-55%; placebo, 34%-44%; p<0.05).ConclusionAt baseline, patients with psoriatic disease experienced clinically important fatigue, more so with PsA (20%-28%) than psoriasis (11%-15%). In guselkumab-treated psoriasis and PsA patients, clinically meaningful improvements in fatigue were achieved at W16 and W24, respectively.References[1]Skoie IM et al. Br J Dermatol. 2017;177:505-12[2]Bjorner JB et al. Curr Med Res Opin. 2007;23:731-9[3]Reich K et al. J Am Acad Dermatol. 2017;76:418-31[4]Deodhar A et al. Lancet. 2020;395:1115-25[5]Mease PJ et al. Lancet. 2020;395:1126-36Disclosure of InterestsJoseph F. Merola Consultant of: AbbVie, Arena, Biogen, Bristol-Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma, Yi-Hsuan Liu Employee of: Janssen Global Services, LLC and may own stock or stock options in Johnson & Johnson, Ya-Wen Yang Employee of: Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, and may own stock or stock options in Johnson & Johnson, Megan Miller Employee of: Janssen Research & Development, LLC and may own stock or stock options in Johnson & Johnson, May Shawi Employee of: Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, and may own stock or stock options in Johnson & Johnson, Daphne Chan Employee of: Janssen Scientific Affairs, LLC and may own stock or stock options in Johnson & Johnson, Saakshi Khattri Speakers bureau: Abbvie, Eli Lilly, UCB, Janssen, Paid instructor for: Abbvie, Eli Lilly, UCB, Janssen, Consultant of: Abbvie, Eli Lilly, UCB, Janssen, Grant/research support from: Pfizer, Abbvie, Leo, BMS, Eli Lilly, Laura Savage Speakers bureau: AbbVie, Almirall, Amgen, Celgene, Celltrion, Eli Lilly, Galderma, Janssen, LEO Pharma, MSD, Novartis, Sanofi and UCB Pharma, Consultant of: AbbVie, Almirall, Amgen, Celgene, Celltrion, Eli Lilly, Galderma, Janssen, LEO Pharma, MSD, Novartis, Sanofi and UCB Pharma, Grant/research support from: Janssen and Pfizer, Wolf-Henning Boehncke Speakers bureau: AbbVie, Almirall, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, and UCB Pharma; and has received a research grant from Pfizer, Consultant of: AbbVie, Almirall, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, and UCB Pharma; and has received a research grant from Pfizer, Chenglong Han Employee of: Janssen Global Services, LLC and may own stock or stock options in Johnson & Johnson
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Mease, P. J., A. Lertratanakul, B. Strober, S. Tsuji, P. Richette, C. Lovan, D. Feng, J. Anderson, and F. Van den Bosch. "POS1032 EFFICACY OF UPADACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS STRATIFIED BY NUMBER OF PRIOR BIOLOGIC DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 788–89. http://dx.doi.org/10.1136/annrheumdis-2021-eular.564.
Full textAbstract:
Background:Upadacitinib (UPA) has shown efficacy and safety in patients (pts) with active PsA in the Phase 3 SELECT-PsA 1 and SELECT-PsA 2 clinical trials.1,2 Historically efficacy has been lower with second- and third-line therapy compared with first-line anti-TNF therapy in PsA;3,4 however, clinical trial data that describe efficacy in pts who have had an inadequate response (IR) to multiple biologic DMARDs (bDMARDs) are limited.Objectives:This analysis assessed the effects of prior bDMARD failure on UPA efficacy in the SELECT-PsA 2 trial.Methods:The SELECT-PsA 2 study enrolled pts with prior IR or intolerance to ≥1 bDMARD (N=642). Pts were randomized to placebo (PBO), UPA 15 mg once daily (QD, UPA15), or UPA 30 mg QD (UPA30). Stable background treatment of ≤2 non-bDMARDs was permitted; background therapy was not required. Only the pts who had IR to ≥1 bDMARD were included in this analysis; pts were subgrouped based on the number of bDMARDs failed prior to enrollment (1, 2, or ≥3). This analysis includes assessment of proportion of pts achieving ACR20/50/70, and change in HAQ-DI, FACIT-Fatigue, and SF-36 Physical Component Summary at Wk 12; static Investigator Global Assessment of Psoriasis of 0 or 1 and at least a 2-point improvement from baseline, PASI75, and change in Self-Assessment of Psoriasis Symptoms at Wk 16; and proportion of pts achieving minimal disease activity (MDA) at Wk 24. Non-responder imputation was used for binary endpoints. Mixed-effects model for repeated measures was used for continuous endpoints. Point estimates and 95% confidence intervals (CIs) of the PBO subtracted treatment effect were calculated.Results:641 pts were randomized and received study drug; 92% were bDMARD-IR: 391 (61%) of pts failed 1 bDMARD, 116 (18%) failed 2 bDMARDs, and 83 (13%) failed ≥3 bDMARDs. In the overall study population, UPA15 and UPA30 demonstrated superiority vs placebo for all endpoints evaluated. In this post hoc analysis, the PBO subtracted treatment effect demonstrates generally consistent efficacy as compared to the overall study population for UPA15 and UPA30 across efficacy endpoints in the subgroups of pts with IR to 1, 2, or ≥3 prior bDMARDs (Figure 1). Due to limited sample sizes for pts with IR to >1 bDMARD and the pt subsets analyzed for psoriasis-related endpoints, results should be interpreted with caution.Conclusion:Upadacitinib demonstrated consistent efficacy in treating clinical manifestations of PsA including musculoskeletal symptoms, psoriasis, physical function, fatigue, and quality of life in pts with IR to 1 or multiple prior bDMARDs. In addition, comprehensive disease control as measured by MDA, was generally consistently achieved with upadacitinib regardless of number of prior bDMARDs tried.References:[1]McInnes IB, et al. Ann Rheum Dis, 2020; 79:12.[2]Genovese MC, et al. Ann Rheum Dis, 2020; 79:139.[3]Costa L, et al. Drugs R D. 2017;17:509-522.[4]Reddy SM, et al. 2016;35:2955-2966.Acknowledgements:AbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial. AbbVie, Inc was the study sponsor, contributed to study design, data collection, analysis & interpretation, and to writing, reviewing, and approval of final version. No honoraria or payments were made for authorship. Medical writing support was provided by Ramona Vladea, PhD of AbbVie Inc.Disclosure of Interests:Philip J Mease Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers, Celgene, Galapagos, Genentech, Gilead, GlaxosmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Sun Pharma, and UCB., Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers, Celgene, Galapagos, Genentech, Gilead, GlaxosmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Sun Pharma, and UCB., Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers, Celgene, Galapagos, Genentech, Gilead, GlaxosmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Sun Pharma, and UCB., Apinya Lertratanakul Shareholder of: AbbVie, Employee of: AbbVie, Bruce Strober Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Ortho Dermatologics, Consultant of: AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Boehringer Ingelheim, Bristol-Myers-Squibb, Cara, Celgene, Dermavant, Dermira, Janssen, Leo, Eli Lilly, Meiji Seika Pharma, Novartis, Pfizer, GlaxoSmithKline, UCB Pharma, Sun Pharma, Ortho Dermatologics, Regeneron, Sanofi-Genzyme, Shigeyoshi Tsuji Speakers bureau: AbbVie Inc., Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB, Consultant of: AbbVie Inc., Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB, Pascal Richette Speakers bureau: AbbVie, Biogen, Janssen, BMS, Roche, Pfizer, Amgen, Sanofi-Aventis, UCB, Lilly, Novartis, and Celgene, Consultant of: AbbVie, Biogen, Janssen, BMS, Roche, Pfizer, Amgen, Sanofi-Aventis, UCB, Lilly, Novartis, and Celgene, Charles Lovan Shareholder of: AbbVie, Employee of: AbbVie, Dai Feng Shareholder of: AbbVie, Employee of: AbbVie, Jaclyn Anderson Shareholder of: AbbVie, Employee of: AbbVie, Filip van den Bosch Speakers bureau: AbbVie Inc., Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB, Consultant of: AbbVie Inc., Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer and UCB.
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Nash, P., P. Richette, L. Gossec, A. Marchesoni, C. T. Ritchlin, K. Kato, E. Mcdearmon-Blondell, et al. "POS1035 UPADACITINIB AS MONOTHERAPY AND IN COMBINATION WITH NON-BIOLOGIC DMARDs FOR THE TREATMENT OF PSORIATIC ARTHRITIS: SUBGROUP ANALYSIS FROM TWO PHASE 3 TRIALS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 790.1–790. http://dx.doi.org/10.1136/annrheumdis-2021-eular.662.
Full textAbstract:
Background:Approximately 40% of PsA patients (pts) on advanced therapy are on monotherapy.1,2 Upadacitinib (UPA) showed efficacy and safety in pts with active PsA in the Phase 3 SELECT-PsA 1 and SELECT-PsA 2 clinical trials.3,4Objectives:Assess efficacy and safety in subgroups of pts treated with UPA as monotherapy or in combination with non-biologic disease-modifying antirheumatic drugs (non-bDMARDs).Methods:The SELECT-PsA program enrolled pts with prior inadequate response (IR) or intolerance to ≥1 non-bDMARD (N=1705) and prior IR or intolerance to ≥1 bDMARD (N=642). Data from both trials was integrated for pts receiving placebo (PBO), UPA 15 mg once daily (QD) and UPA 30 mg QD. Stable background treatment of ≤2 non-bDMARDs was permitted, but not required. Analysis includes UPA monotherapy vs combination therapy for endpoints: ACR20/50/70 responses and change from baseline in pain and HAQ-DI (Wk 12); Static Investigator Global Assessment of Psoriasis of 0 or 1 and at least a 2-point improvement from baseline and PASI75/90/100 responses (Wk 16); proportion of pts achieving resolution of enthesitis, dactylitis, and minimal disease activity (Wk 24). Binary outcomes, using the Cochran-Mantel-Haenszel-method and continuous outcomes, using mixed-effects model, were analyzed for repeated measures in the subgroups of UPA monotherapy and combination therapy. Point estimates and 95% confidence intervals (CIs) of PBO subtracted treatment effect were calculated. Treatment-emergent adverse events (TEAEs) were analyzed.Results:Of 1916 pts, 574 (30%) received monotherapy and 1342 (70%) received combination therapy; 84% in combination therapy group received MTX +/- another non-bDMARD. Both UPA monotherapy and combination therapy led to improvements in efficacy vs PBO and across endpoints, for each dose, generally consistent point estimates of PBO subtracted treatment effect and associated overlapping CIs were observed (Figure 1). Generally, frequency of AEs and serious AEs, were comparable with UPA administered as monotherapy and combination therapy (Table 1). Frequency of AEs of serious infections and hepatic disorder were lower with monotherapy while frequency of AEs leading to discontinuation of study drug were lower with combination therapy. Most hepatic disorders were transient transaminase elevations.Conclusion:In the SELECT PsA trials, efficacy and safety of UPA was generally consistent when administered as monotherapy or when given in combination with non-bDMARDs. Results from this analysis support the use of UPA with or without concomitant non-bDMARDs.References:[1]Ianculescu I and Weisman MH, Clin Exp Rheumatol 2015; 33:S94–S97.[2]Mease PJ, et al. RMD Open 2015; 1:e0000181.[3]McInnes IB, et al. Ann Rheum Dis, 2020; 79:12.[4]Genovese MC, et al. Ann Rheum Dis, 2020; 79:139.Acknowledgements:AbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial. AbbVie, Inc was the study sponsor, contributed to study design, data collection, analysis & interpretation, and to writing, reviewing, and approval of final version. No honoraria or payments were made for authorship. Medical writing support was provided by Ramona Vladea of AbbVie Inc.Disclosure of Interests:Peter Nash Speakers bureau: AbbVie, BMS, Roche, Pfizer, Janssen, Amgen, Sanofi-Aventis, UCB, Eli Lilly, Novartis, and Celgene, Consultant of: AbbVie, BMS, Roche, Pfizer, Janssen, Amgen, Sanofi-Aventis, UCB, Eli Lilly, Novartis, and Celgene, Grant/research support from: AbbVie, BMS, Roche, Pfizer, Janssen, Amgen, Sanofi-Aventis, UCB, Eli Lilly, Novartis, and Celgene, Pascal Richette Speakers bureau: AbbVie, Biogen, Janssen, BMS, Roche, Pfizer, Amgen, Sanofi-Aventis, UCB, Lilly, Novartis, and Celgene, Consultant of: AbbVie, Biogen, Janssen, BMS, Roche, Pfizer, Amgen, Sanofi-Aventis, UCB, Lilly, Novartis, and Celgene, Laure Gossec Speakers bureau: Abbvie, Amgen, Biogen, BMS, Celgene, Lilly, Novartis, Pfizer, Janssen, Sandoz, Sanofi-Aventis, UCB, Consultant of: Abbvie, Amgen, Biogen, BMS, Celgene, Lilly, Novartis, Pfizer, Janssen, Sandoz, Sanofi-Aventis, UCB, Grant/research support from: Abbvie, Amgen, Biogen, BMS, Celgene, Lilly, Novartis, Pfizer, Janssen, Sandoz, Sanofi-Aventis, UCB, Antonio Marchesoni Speakers bureau: AbbVie, BMS, Celgene, Eli-Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, BMS, Celgene, Eli-Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Novartis, UCB, Grant/research support from: UCB, Koji Kato Shareholder of: AbbVie, Employee of: AbbVie, Erin McDearmon-Blondell Shareholder of: AbbVie, Employee of: AbbVie, Elizabeth Lesser Shareholder of: AbbVie, Employee of: AbbVie, Reva McCaskill Shareholder of: AbbVie, Employee of: AbbVie, Dai Feng Shareholder of: AbbVie, Employee of: AbbVie, Jaclyn Anderson Shareholder of: AbbVie, Employee of: AbbVie, Eric Ruderman Consultant of: AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, and Pfizer.
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Seridi, L., M. Cesaroni, M. J. Loza, J. Schreiter, K. Sweet, Y. Orlovsky, I. Baribaud, et al. "OP0161 ASSOCIATION OF BASELINE CYTOTOXIC GENE EXPRESSION WITH USTEKINUMAB RESPONSE IN SYSTEMIC LUPUS ERYTHEMATOSUS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 101–2. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2407.
Full textAbstract:
Background:Systemic Lupus Erythematous (SLE) is a clinically and biologically diverse disease, for which only one new therapy has been approved in the past 60 years. In a phase 2 trial on patients with mild-to-moderate SLE, ustekinumab (UST) improved clinical and laboratory measures of disease activity compared with placebo (PBO).1Objectives:We previously reported an association of IFN-γ reduction with response to UST,2suggesting an impact on the IL12/Th1 axis. To extend these findings, we performed unbiased transcriptomic analysis from baseline whole blood samples to identify genes that discriminate UST responders (UST-R) from non-responders (UST-NR) using the primary endpoint of Systemic Lupus Erythematosus Responder Index (SRI)-4 at week 24 to define response.Methods:UST was studied in a Ph2 PBO-controlled study of 102 patients with seropositive SLE and active disease despite standard therapy. Patients were randomized 3:2 to receive IV UST 6 mg/kg or placebo followed by subcutaneous injections of UST 90 mg or PBO every 8 weeks. Whole blood gene expression at baseline was measured via microarray using RNA samples from 100 patients, as samples from 2 patients failed quality control. An unbiased approach was used to identify gene signatures present at baseline that associate with UST response. Recombinant IL-12 or IL-23 was incubatedin vitrowith whole blood from 6 healthy donors for 24h and RNA-Seq was performed to determine the effect of these treatments on representative genes comprising the UST response signature.Results:A non-biased machine learning algorithm identified a 9-gene whole blood signature composed primarily of cytotoxic cell-associated transcripts (PRF1, KLRD1, GZMH, NKG7, GNLY, FGFBP2, TRGC2, TARP, TRGV2) that was enriched at baseline in UST-R vs UST-NR. By Gene Set Variation Analysis, the cytotoxic signature enrichment in UST-NR was less at baseline than both UST-R and a healthy control cohort (P=0.0087, P=0.056, respectively), whereas UST-R cytotoxic gene enrichment was similar to healthy controls (P=0.31). No significant difference in cytotoxic signature enrichment was observed at baseline between PBO responders and PBO non-responders or healthy controls (Figure). Enrichment levels of the cytotoxic gene signature remained stable over time in PBO and UST-NR groups while a trend of decreased cytotoxic signature was observed in UST-R, although never reaching levels seen in UST-NR. To begin to understand the relationship between IL-12 and IL-23, the targets of UST, and the cytotoxic signature, whole blood was stimulated with these cytokinesin vitro. Recombinant IL-12, but not IL-23, resulted in increased expression of representative members of this cytotoxic gene signature.Conclusion:We identified a novel cytotoxic signature in baseline blood samples that associated with UST response in SLE. The observation that IL-12 can increase this signaturein vitroand that IL-12 is a robust inducer of cytotoxic cell activity3as well as IFN-γ3suggests an important role of IL-12 blockade in the mechanism of action of UST in SLE.References:[1]van Vollenhoven RF. Lancet. 2018;392:1330-39[2]Jordan. ACR 2018 Abstract # 2951[3]G. Trinchieri. Nat Rev Immunol. 2003;3:133-46Figure.Disclosure of Interests:Loqmane Seridi Employee of: Janssen Research & Development, LLC, Matteo Cesaroni Employee of: Janssen Research & Development, LLC, Matthew J Loza Employee of: Janssen Research & Development, LLC, Jessica Schreiter Employee of: Janssen Research & Development, LLC, Kristen Sweet Employee of: Janssen Research & Development, LLC, Yevgeniya Orlovsky Employee of: Janssen Research & Development, LLC, Spring House, PA, United States of America, Isabelle Baribaud Employee of: Janssen Research & Development, LLC, Ashley Orillion Employee of: Janssen Research & Development, LLC, Peter Lipsky Consultant of: Horizon Therapeutics, Ronald van Vollenhoven Grant/research support from: AbbVie, Amgen, Arthrogen, Bristol-Myers Squibb, GlaxoSmithKline (GSK), Janssen Research & Development, LLC, Lilly, Pfizer, Roche, and UCB, Consultant of: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Crescendo Bioscience, GSK, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, UCB and Vertex, Speakers bureau: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Crescendo Bioscience, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, Vertex, Bevra H. Hahn Grant/research support from: Janssen Research & Development, LLC, George Tsokos Grant/research support from: Janssen Research & Development, LLC, Marc Chevrier Employee of: Janssen Research & Development, LLC, Shawn Rose Employee of: Janssen Research & Development, LLC, Frederic Baribaud Shareholder of: Janssen Research & Development, LLC, Employee of: Janssen Research & Development, LLC, Jarrat Jordan Employee of: Janssen Research & Development, LLC
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Baraliakos, X., E. Pournara, L. Gossec, H. Marzo-Ortega, P. J. Mease, R. White, E. O’brien, B. Schulz, and L. C. Coates. "POS0930 SECUKINUMAB IN PATIENTS WITH PSORIATIC ARTHRITIS AND AXIAL MANIFESTATIONS: PREDICTORS OF RESPONSE FROM THE DOUBLE-BLIND, RANDOMISED, PHASE 3B MAXIMISE TRIAL." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 728.1–728. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2456.
Full textAbstract:
Background:Psoriatic arthritis (PsA) is a heterogeneous disease with variability of response to different therapeutic modalities.1 Identifying potential demographic and disease characteristics as predictors of treatment response may define personalised treatment optimisation strategies.2–3Objectives:This post-hoc exploratory analysis of the MAXIMISE trial4 investigated the differential treatment effect of demographics and baseline characteristics as predictive factors in biologic naïve patients with active PsA and symptoms of active spinal disease.Methods:The full analysis set (FAS) comprised of all patients from the randomised set assigned to study treatment, fulfilling the predefined clinical criteria for active axial disease and for whom Assessment of SpondyloArthritis International Society (ASAS) 20 data were available at Week 12. The research hypothesis was that the odds ratio associated with the effect of treatment on ASAS20 responder status at Week 12 would be different depending on 12 pre-specified predictor variables. A logistic regression model was initially fitted to the FAS that included 12 pre-specified covariates. A second logistic regression model was then fitted to the FAS that allowed for all 12 pre-specified variables to interact with treatment.5 The log-likelihood of the two fitted models were compared using a likelihood ratio test at a pre-specified significance level of 20% (i.e. P-value ≤0.20) to test whether any of the predefined variables interacted with treatment. If the above test was statistically significant at the 20% level of statistical significance the variables of the second model were formally examined to determine whether the overall effect of treatment is not applicable. Three forest plots were produced, one for each treatment group. Hypothesis tests were employed to determine the strength of evidence for each individual variable.Results:The likelihood ratio test provided evidence against the assumption that the overall effect of treatment is applicable to all patients (P-value = 0.08). Notably, the odds of being an ASAS20 responder if nail dystrophy is present at baseline were 3 times greater in the secukinumab 150 mg group and 5 times greater in the 300 mg group compared with placebo (interaction P-value = 0.029). Although males fare worse than females in the placebo group, in the secukinumab 150 mg and 300 mg treatment groups the odds of being a responder were similar to females (interaction P-value = 0.039). Current smokers were less likely to be ASAS20 responders compared to never smokers regardless of treatment group (interaction P-value = 0.589) (Figure 1). Age, CRP level, Berlin MRI spine/SIJ score, time since first axial signs, number of swollen joints, new bone formation and BMI did not show a differential treatment effect on ASAS20 responses.Conclusion:Of the 12 baseline variables of a unique population of 473 PsA patients with active axial disease diagnosed by clinical criteria, our analyses showed evidence of a differential treatment effect most notably for nail dystrophy suggesting that the presence of nail dystrophy may predict a better response to secukinumab in PsA patients with axial manifestations.References:[1]Coates LC, Helliwell PS. Clin Med (Lond). 2017;17(1):65–70.[2]Watson DS, et al. BMJ. 2019;364:l886.[3]Hügle M, et al. Rheumatol Adv Pract. 2020;4(1):rkaa005.[4]Baraliakos X, et al. Ann Rheum Dis. Published Online First: 17 Dec 2020. doi:10.1136/annrheumdis-2020-218808.[5]Peto R, et al. Br J Cancer. 1977;35(1):1–39.Figure 1.Forest plots of the adjusted odds ratio by treatment using interaction modelDisclosure of Interests:Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Celgene, Chugai, MSD, Novartis, Pfizer, and UCB., Consultant of: AbbVie, BMS, Celgene, Chugai, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB., Grant/research support from: AbbVie, and Novartis., Effie Pournara Shareholder of: Novartis, Employee of: Novartis, Laure Gossec Consultant of: AbbVie, Amgen, BMS, Biogen, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, and UCB., Grant/research support from: Amgen, Lilly, Janssen, Pfizer, Sandoz, Sanofi, and Galapagos., Helena Marzo-Ortega Consultant of: Janssen, Novartis, AbbVie, Celgene, Lilly, Pfizer, Takeda and UCB., Grant/research support from: Janssen, Novartis, AbbVie, Celgene, Lilly, Pfizer, Takeda and UCB., Philip J Mease Speakers bureau: AbbVie, Amgen, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer and UCB., Consultant of: AbbVie, Amgen, BMS, Boehringer Ingelheim, Galapagos, Celgene, Genentech, Gilead, Janssen, Lilly, Novartis, Pfizer, SUN Pharma, and UCB., Grant/research support from: AbbVie, Amgen, BMS, Celgene, Galapagos, Genentech, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, SUN, and UCB., Roisin White Shareholder of: Novartis, Employee of: Novartis, Eamonn O’Brien Shareholder of: Novartis, Employee of: Novartis, Barbara Schulz Employee of: Novartis, Laura C Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Gilead, Eli Lilly, Janssen, Medac, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB., Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Pfizer, and Novartis.
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Helliwell, P., L. C. Coates, F. Van den Bosch, D. D. Gladman, L. Gheyle, M. Trivedi, M. Alani, F. O. Le Brun, R. Besuyen, and P. J. Mease. "POS1038 THE EFFECT OF FILGOTINIB ON ENTHESITIS: 100-WEEK DATA FROM AN OPEN-LABEL EXTENSION STUDY IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 792.2–793. http://dx.doi.org/10.1136/annrheumdis-2021-eular.884.
Full textAbstract:
Background:Filgotinib (FIL), a novel preferential Janus kinase 1 inhibitor, was assessed in patients with active psoriatic arthritis (PsA) in the 16-week, Phase 2, EQUATOR trial (NCT03101670).1 EQUATOR2 (NCT03320876) is the open-label extension (OLE). As previously reported, an interim analysis of the OLE showed that the majority of patients had clinical resolution of enthesitis by Week 52.2Objectives:This post-hoc analysis evaluated the effect of FIL on clinical enthesitis after 100 weeks of treatment in the OLE, as assessed using the Leeds Enthesitis Index (LEI) and Spondyloarthritis Research Consortium of Canada (SPARCC) index, and evaluated the discriminatory capacity of the two indices. In addition, we assessed which of the sites included in LEI and SPARCC were most frequently involved and whether treatment effect was consistent across sites.Methods:In EQUATOR, patients with active moderate-to-severe PsA (≥5 swollen joints and ≥5 tender joints, fulfilling Classification for PsA criteria) were randomised 1:1 to receive oral FIL 200 mg or placebo (PBO) once daily (QD) for 16 weeks. At Week 16, all patients could continue into the OLE, receiving FIL 200 mg QD for up to an additional 304 weeks. We compared changes from core baseline in LEI and SPARCC measures, the effect on enthesitis at sites included in LEI and SPARCC assessments and the discriminatory capacity of both enthesitis indices.Results:Of 131 patients randomised to EQUATOR, 122 entered the OLE. There was strong agreement between LEI and SPARCC at baseline. While most patients had enthesitis at baseline according to either index (76/131 [58.0%] by LEI; 85/131 [64.9%] by SPARCC), a minority had enthesitis at a large number of sites (6.9% with 5–6 LEI sites; 12.2% with ≥9 SPARCC sites). The sites most frequently involved at baseline were the lateral epicondyle humerus and Achilles tendon, sites common to both LEI and SPARCC. There was greater variability in the change from baseline to Week 16 in SPARCC compared with LEI (Table 1). LEI showed a greater discriminatory capacity than SPARCC when change from baseline was compared for FIL vs PBO at Week 16, as shown by higher absolute standardised mean difference: −0.70 (LEI) and −0.30 (SPARCC) (observed cases; Table 1). Subgroup analyses indicated that the treatment effect of FIL vs PBO at Week 16 for all sites was consistent with the overall treatment effect seen for LEI or SPARCC, and indicative of an improvement with FIL vs PBO for nearly all sites. The proportion of patients with enthesitis decreased from baseline up to OLE Week 100 (Figure 1). There were no major differences in long-term effect on enthesitis between sites.Conclusion:FIL improved enthesitis consistently across sites compared with PBO. Rapid improvement in enthesitis was seen up to Week 16 of the core study and improvements continued up to Week 52, after which responses were generally stable up to Week 100. LEI assesses fewer locations than SPARCC, but reassuringly captured the sites most commonly affected by enthesitis; LEI also had greater discriminatory capacity.References:[1]Mease P, et al. Lancet 2018;392:2367–77[2]Mease P, et al. Arthritis Rheumatol 2020;72(suppl 10): abstract 0910Figure 1.Acknowledgements:EQUATOR and EQUATOR2 were sponsored by Galapagos NV (Mechelen, Belgium) and co-funded by Galapagos NV and Gilead Sciences, Inc (Foster City, CA, USA). Eline Vetters, Leen Gilles, Benjamin Pett and his team, all employees of Galapagos, provided assistance with statistical analyses. Medical writing/editorial support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), and funded by Galapagos NV.Disclosure of Interests:Philip Helliwell Speakers bureau: Janssen, Novartis, Paid instructor for: Pfizer, Consultant of: Eli Lilly, Laura C Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Novartis, and Pfizer, Filip van den Bosch Consultant of: AbbVie, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Merck and UCB, Dafna D Gladman Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Lien Gheyle Shareholder of: Galapagos, Employee of: Galapagos, Mona Trivedi Shareholder of: Gilead Sciences, Amgen, Employee of: Gilead Sciences, Muhsen Alani Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Franck Olivier Le Brun Shareholder of: Galapagos, Employee of: Galapagos, Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer, SUN and UCB.
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Curtis, J., I. McInnes, P. Rahman, D. D. Gladman, F. Yang, S. Peterson, A. Kollmeier, et al. "AB0881 Guselkumab Provides Sustained Improvements in Health-Related Quality of Life in Patients With Active Psoriatic Arthritis Through 2 Years of DISCOVER-2." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 1563.2–1564. http://dx.doi.org/10.1136/annrheumdis-2022-eular.733.
Full textAbstract:
BackgroundPsoriatic arthritis (PsA), a chronic inflammatory disease characterized by peripheral arthritis, axial inflammation, dactylitis, enthesitis, and skin/nail psoriasis, is associated with reduced health-related quality of life (HRQoL).ObjectivesTo assess long-term effect of guselkumab (GUS), a human monoclonal antibody that selectively targets the interleukin (IL)-23p19 subunit, on HRQoL of bio-naïve PsA patients (pts) who participated in the Phase 3 2-year DISCOVER-2 trial.1MethodsPts with active PsA despite nonbiologic disease-modifying antirheumatic drugs (DMARDs) and/or nonsteroidal anti-inflammatory drugs (NSAIDs) received GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or placebo (PBO). At W24, PBO pts crossed over to GUS 100 mg Q4W. HRQoL was assessed using the pt-reported EuroQoL-5 Dimension-5 Level (EQ-5D-5L) questionnaire index and EuroQol Visual Analog Scale (EQ-VAS), widely used and complimentary tools that allow pts to provide a global assessment of their HRQoL. The EQ-5D-5L index assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression; an index score is derived ranging from 0 (death) to 1 (perfect health).2 EQ-VAS assesses pt health state on a scale of 0-100, with higher scores indicating better health. Using mixed effects models for repeated measures (MMRM), least squares (LS) mean changes from baseline in the EQ-5D-5L index and EQ-VAS through W100 were assessed. Observed changes from baseline were evaluated; in pts who met treatment failure rules before W24 and in pts who discontinued with missing data after W24, changes from baseline were imputed as 0.ResultsGUS-treated pts achieved greater improvements in pt-reported health status than PBO at both W16 and W24 when evaluated using both the EQ-5D-5L index score and the EQ-VAS. The improvements by GUS in EQ-5D-5L index scores through W24 (0.12 for GUS Q4W/Q8W vs 0.05 for PBO; each nominal p<0.0001) were maintained with continued GUS through 2 years (0.15 for GUS Q4W/Q8W) (Table 1). PBO-treated pts who started GUS at W24 reported comparable improvements in their HRQoL by W52 (0.12), with maintenance though W100 (0.14). Similar results were observed with EQ-VAS (Figure 1). W24 improvements in EQ-VAS scores were greater following GUS treatment (18.2/18.4 GUS Q4W/Q8W) vs PBO (6.8; nominal p<0.0001). EQ-VAS scores continued to improve with GUS through 2 years (25.0/24.6 GUS Q4W/Q8W). Likewise, PBO-treated pts who crossed over to GUS at W24 experienced improvements in HRQoL by W52 (18.8), with maintenance through W100 (21.2).Table 1.LS mean change from baseline through W100 in EQ-5D-5L indexGUS 100mg Q4W(W0-100)GUS 100mg Q8W(W0-100)PBO → GUS 100 mg Q4WPBO(W0-24)GUS(W24-100)Week162410016241001624100N243244243247246248244244244LS mean change (95% CI)0.10 (0.09,0.12)0.12 (0.1,0.13)0.15 (0.13,0.16)0.11 (0.1,0.13)0.12 (0.1,0.13)0.15 (0.13,0.17)0.06 (0.04,0.07)0.05 (0.04,0.07)0.14 (0.12,0.16) Diff vs. PBO0.04 (0.02,0.06)0.06 (0.04,0.09)--0.05 (0.03,0.07)0.06 (0.04,0.08)-------- Nominal p-value<0.0001<0.0001--<0.0001<0.0001--------CI=Confidence interval; Diff=DifferenceConclusionIn bio-naïve pts with active PsA receiving GUS, earlier improvements (at the first timepoint assessed) in self-reported HRQoL measures were sustained through 2 years.References[1]Mease PJ, et al. Lancet. 2020;395:1126–36.[2]EuroQol Group. 1990;16:199-208.Disclosure of InterestsJeffrey Curtis Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, CorEvitas, Eli Lilly, Janssen, Myriad, Novartis, Pfizer, Sanofi, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, CorEvitas, Eli Lilly, Janssen, Myriad, Novartis, Pfizer, Sanofi, and UCB, Iain McInnes Shareholder of: Causeway Therapeutics, and Evelo Compugen, Consultant of: Astra Zeneca, AbbVie, Amgen, Bristol-Myers Squibb, Cabaletta, Compugen, Eli Lilly, Gilead, GSK, Janssen, Novartis, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: Astra Zeneca, Amgen, Bristol-Myers Squibb, Eli Lilly, GSK, Janssen, Novartis, Roche, and UCB, Proton Rahman Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: Janssen and Novartis, Dafna D Gladman Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Eli Lilly, Janssen, Pfizer, and UCB, Feifei Yang Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC (a wholly owned subsidiary of Johnson & Johnson), Steve Peterson Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC (a wholly owned subsidiary of Johnson & Johnson), Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC (a wholly owned subsidiary of Johnson & Johnson), Natalie Shiff Shareholder of: AbbVie, Gilead, and Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC (a wholly owned subsidiary of Johnson & Johnson), Chenglong Han Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC (a wholly owned subsidiary of Johnson & Johnson), May Shawi Shareholder of: Johnson & Johnson, Employee of: Immunology Global Medical Affairs, Janssen Pharmaceutical Companies (a wholly owned subsidiary of Johnson & Johnson), William Tillett Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Eli Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Eli Lilly, Janssen, and UCB, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN Pharma, and UCB
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Kristensen, L. E., P. C. Taylor, V. Navarro-Compán, M. Magrey, J. C. Cappelleri, A. G. Bushmakin, A. Yndestad, and O. Dina. "AB0750 Back pain and morning stiffness as mediators of tofacitinib treatment effect on fatigue in patients with ankylosing spondylitis: a mediation analysis." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 1500.1–1500. http://dx.doi.org/10.1136/annrheumdis-2022-eular.28.
Full textAbstract:
BackgroundFatigue is a prevalent symptom of ankylosing spondylitis (AS)1 and can contribute to higher levels of disease, disability and poor health-related quality of life.2 Back pain and morning stiffness are also commonly reported symptoms.3 Tofacitinib is an oral Janus kinase inhibitor for the treatment of adult patients (pts) with AS. In randomised studies, pts with active AS treated with tofacitinib experienced greater improvements in fatigue, back pain and morning stiffness at Week 12 and 16 of treatment compared with placebo (PBO).4,5 Treatment of these symptoms is a priority for pts with AS and their healthcare providers, however, the mechanisms underlying the interrelationships between fatigue, back pain, morning stiffness and treatment are unclear.ObjectivesTo describe the interrelationships between fatigue, back pain, morning stiffness and tofacitinib treatment in pts with AS, using mediation modelling.MethodsData from Phase 2 (NCT01786668)4 and Phase 3 (NCT03502616)5 studies of pts with active AS treated with tofacitinib 5 mg twice daily (BID) or PBO were used. Mediation modelling, a statistical method to assess the extent to which the effect of an independent variable on a dependent variable is indirect, via identified mediators, or direct, capturing all other (unmeasured) effects, was applied.6,7 The initial model included: treatment as the independent binary variable (tofacitinib 5 mg BID vs PBO); fatigue (measured by Functional Assessment of Chronic Illness Therapy-Fatigue) as the dependent variable; mediators included back pain (measured by total back pain/nocturnal spinal pain [numerical rating scale, 0–10]) and morning stiffness (represented by the mean of Bath Ankylosing Spondylitis Disease Activity Index questions 5 and 6).ResultsPooled data from 370 pts were included in the analysis. The initial model showed that 57.5% (p<0.001) of the tofacitinib treatment effect on fatigue was mediated via back pain and morning stiffness (indirect effect); mediation via morning stiffness alone was 49.7% (p<0.01), and 21.2% (p=0.02) via back pain alone. The effect of treatment attributable to factors other than back pain and morning stiffness (ie, direct effect) was not statistically significant (-28.4%; p=0.33). As a result, the initial model was re-specified to exclude the direct treatment effect on fatigue. In the re-specified model (Figure 1), 44.0% (p<0.0001) of the indirect effect of tofacitinib on fatigue was mediated via back pain and morning stiffness; mediation via morning stiffness alone was 40.0% (p<0.001), and 16.0% (p<0.01) via back pain alone. Analyses of the individual study data gave results generally consistent with those from the pooled data.ConclusionOverall, indirect pathways via morning stiffness accounted for ~84% of the effect of tofacitinib treatment on fatigue: (1) treatment affects morning stiffness, which impacts fatigue; and (2) treatment affects morning stiffness, which affects back pain and, ultimately, back pain affects fatigue. The indirect pathway via back pain alone accounted for ~16% of treatment effect on fatigue. These results suggest that in tofacitinib-treated pts with AS, improvements in fatigue are fully mediated through combined treatment effects on morning stiffness and back pain.References[1]Schneeberger EE et al. Clin Rheumatol 2015; 34: 497-501.[2]Connolly D et al. Occup Ther Int 2019; 2019: 3027280.[3]Braun J. Rheumatology (Oxford) 2018; 57: vi1-vi3.[4]van der Heijde D et al. Ann Rheum Dis 2017; 76: 1340-1347.[5]Deodhar A et al. Ann Rheum Dis 2021; 80: 1004-1013.[6]Richiardi L et al. Int J Epidemiol 2013; 42: 1511-1519.[7]Cappelleri JC et al. Boca Raton, FL: CRC Press, 2013.AcknowledgementsStudy sponsored by Pfizer Inc. Medical writing support was provided by Robyn Wilson, CMC Connect, and funded by Pfizer Inc.Disclosure of InterestsLars Erik Kristensen Speakers bureau: AbbVie, Biogen, Eli Lilly, Galapagos NV, Gilead Sciences, Janssen, Pfizer Inc, Sanofi, UCB, Consultant of: AbbVie, Biogen, Eli Lilly, Galapagos NV, Gilead Sciences, Janssen, Pfizer Inc, Sanofi, UCB, Grant/research support from: AbbVie, Eli Lilly, Pfizer Inc, UCB, Peter C. Taylor Consultant of: AbbVie, BMS, Biogen, Celltrion, Eli Lilly, Fresenius, Galapagos NV, Gilead Sciences, GSK, Janssen, Nordic Pharma, Pfizer Inc, Sanofi, UCB, Grant/research support from: Celgene, Galapagos, Victoria Navarro-Compán Speakers bureau: AbbVie, Janssen, Lilly, MSD, Pfizer Inc, UCB, Consultant of: AbbVie, Janssen, Lilly, Moonlake, MSD, Pfizer Inc, UCB, Grant/research support from: AbbVie, Novartis, Marina Magrey Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Grant/research support from: AbbVie, UCB, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Arne Yndestad Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Oluwaseyi Dina Shareholder of: Pfizer Inc, Employee of: Pfizer Inc.
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Kavanaugh, A., X. Baraliakos, S. Gao, W. Chen, K. Sweet, S. D. Chakravarty, Q. Song, M. Shawi, F. Behrens, and P. Rahman. "POS0969 GENETIC AND MOLECULAR DISTINCTIONS BETWEEN AXIAL PSORIATIC ARTHRITIS AND ANKYLOSING SPONDYLITIS." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 791.2–792. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1500.
Full textAbstract:
BackgroundPsoriatic arthritis (PsA) and ankylosing spondylitis (AS) represent the prototypical spondyloarthritides. PsA patients may also suffer from axial disease (axPsA). Despite overlapping symptoms, axPsA and AS may be distinct disorders with differing clinical manifestations, genetic associations, and radiographic findings.1 These disorders also respond differently to immunomodulatory therapies such as anti-interleukin (IL)-23 inhibitors. While guselkumab, a human monoclonal antibody targeting the IL-23p19 subunit, improved symptoms of axPsA,2 risankizumab, a humanized monoclonal antibody targeting the IL-23p19 subunit, did not show improvement in the primary endpoint of proportion of AS patients achieving an Assessment of SpondyloArthritis International Society 40% (ASAS40) response at week (W) 12.3ObjectivesTo understand molecular distinctions between axPsA and AS to differentiate these diseases and guide treatment choice.MethodsWhole blood and serum samples were collected from consenting patients in the NCT03162796/NCT0315828 studies of guselkumab in PsA and the NCT02437162/NCT02438787 studies of ustekinumab in AS. axPsA patients were investigator-verified as having magnetic resonance imaging- or pelvic x-ray-confirmed sacroiliitis at screening (locally read). Human leukocyte antigen (HLA) genotypes were determined by RNA sequencing, limited to Caucasian patients to reduce genetic variability,4 and select serum cytokine levels were analyzed alongside samples from healthy individuals. Differential prevalence of HLA alleles in axPsA versus AS was determined using a Fisher’s Exact test. Statistical significance of differential baseline serum cytokine expression among axPsA versus non-axPsA versus AS patients, and of guselkumab effect on serum cytokine reduction versus placebo among axPsA and non-axPsA patients, were determined with a generalized linear model performed on log2-transformed data. Biomarker data from guselkumab every-4-weeks and every-8-weeks treatment arms were pooled.ResultsAmong the 186/234 Caucasian axPsA/AS patients with available data, 34%/15% were female, 70%/14% used methotrexate at baseline, mean serum C-reactive protein (CRP) levels were 2.8/2.4 mg/dL and mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores were 6.4/7.5, respectively. Aside from race, baseline demographics and disease characteristics were representative of the overall population. The prevalence of class I HLA allele -B27, -C01, and -C02 carriers was significantly lower in axPsA than AS patients (30.7% versus 92.3%, p<0.001; 5.9% versus 31.6%, p<0.001; and 28.0% versus 62.0%, p<0.001, respectively), while the prevalence of HLA-C06 was significantly higher in axPsA than AS populations (36.0% versus 8.6%, p<0.001). Baseline serum levels of IL-17A and IL-17F were significantly higher in axPsA (N=71) than in AS (N=58) patients (p<0.01 and p<0.001, respectively). Comparable IL-17A/F expression was seen for axPsA and non-axPsA (N=229) patients (both p=not significant). Significant and comparable reductions from baseline in serum IL-17A/F in axPsA and non-axPsA patients were seen with guselkumab treatment (axPsA N=41, non-axPsA N=160) versus placebo (axPsA N=30, non-axPsA N=69) at W4/24 (all p<0.05).ConclusionAdults with axPsA and AS exhibit different genetic risk factors and serum IL-17 levels, supporting the concept of distinct disorders. Guselkumab demonstrated significant pharmacodynamic effects in axPsA patients that aligned with such effects in non-axPsA patients, consistent with observed clinical improvement.2References[1]Feld et al. Nat Rev Rheumatol. 2018;14(6):363-371.[2]Mease et al. Lancet Rheumatol. 2021;3(10)E715-E723.[3]Baeten et al. Ann Rheum Dis. 2018;77(9):1295-1302.[4]Buchkovich et al. Genome Med. 2017;9(86).Disclosure of InterestsArthur Kavanaugh Consultant of: AbbVie, Amgen, BMS, Genentech, Janssen, Eli Lilly, Merck, Novartis, Pfizer and UCB, Xenofon Baraliakos Consultant of: AbbVie, Chugai, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, MSD, and Novartis, Sheng Gao Employee of: Janssen Research & Development, LLC, and may own stock or stock options in Johnson & Johnson, Warner Chen Employee of: Janssen Research & Development, LLC, and may own stock or stock options in Johnson & Johnson, Kristen Sweet Employee of: Janssen Research & Development, LLC, and may own stock or stock options in Johnson & Johnson, Soumya D Chakravarty Employee of: Janssen Scientific Affairs, LLC, and may own stock or stock options in Johnson & Johnson, Qingxuan Song Employee of: Janssen Research & Development, LLC, and may own stock or stock options in Johnson & Johnson, May Shawi Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, and may own stock or stock options in Johnson & Johnson, Frank Behrens Speakers bureau: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Genzyme, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Genzyme, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: Celgene, Chugai, Janssen, Pfizer, and Roche, Proton Rahman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: Janssen, research grants from Janssen and Novartis
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Curtis, J., I. Mcinnes, S. Peterson, P. Agarwal, F. Yang, A. Kollmeier, E. C. Hsia, et al. "POS1026 GUSELKUMAB PROVIDES SUSTAINED IMPROVEMENTS IN WORK PRODUCTIVITY AND NON-WORK ACTIVITY IN PATIENTS WITH PSORIATIC ARTHRITIS: RESULTS THROUGH 1 YEAR OF A PHASE 3 TRIAL." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 782.2–783. http://dx.doi.org/10.1136/annrheumdis-2021-eular.244.
Full textAbstract:
Background:DISCOVER-2 was a Phase 3 trial of the first-in-class anti-IL-23-specific mAb guselkumab (GUS) in patients (pts) with psoriatic arthritis (PsA). PsA impacts patients’ productivity at work and in daily activity.1Objectives:To evaluate the effect of GUS on work productivity and daily activity in DISCOVER-2 through 1 year using the Work Productivity and Activity Impairment Questionnaire: PsA (WPAI- PsA).Methods:Bio-naïve adults with active PsA despite nonbiologic DMARDs &/or NSAIDs received subcutaneous GUS 100 mg every 4 weeks (Q4W); GUS 100 mg W0, W4, then Q8W; or placebo (PBO). At W24, PBO pts crossed over to GUS 100 mg Q4W. WPAI-PsA assesses PsA-related work time missed (absenteeism), impairment while working (presenteeism), impaired overall work productivity (absenteeism + presenteeism), and daily activity during the previous week. A shift analysis evaluated proportions of pts employed vs unemployed (regardless of desire to work) over time. Among pts working at baseline, least-squares (LS) mean changes from baseline in WPAI-PsA domains were determined using a mixed-effects model for repeated measures analysis, whereby mean changes in WPAI-PsA domains were calculated for each multiple imputation (MI) dataset using an analysis of covariance (ANCOVA); the reported LSmean is the average of all MI datasets. Also, among pts employed at baseline, indirect savings from improved overall work productivity were estimated using 2020 EU mean yearly wage estimate (all occupations).2Results:In pts working at baseline, significant improvement in work productivity and non-work activity vs PBO was observed at W24. Productivity gains seen with GUS at W24 continued to improve through 1 year (Table 1). Shift analysis showed relatively stable employment in pts employed at baseline (62% of shift analysis cohort) through 1 year of GUS (>91% continued to work when assessed at W16, W24, and W52 [data not shown]). For those unemployed at baseline (38% of cohort), the proportion of pts working increased by ~10% following 1 year of GUS (Figure 1). Potential yearly indirect savings from improved overall work productivity were: €7409 GUS Q4W and €7039 GUS Q8W vs €4075 PBO at W24 and were €8520 GUS Q4W, €9632 GUS Q8W, and €6668 PBO→GUS Q4W at W52.Conclusion:Improvement in work productivity and non-work activity was greater with GUS vs PBO among pts with active PsA through W52. Improvements demonstrated may result in reduction in PsA costs associated with work productivity.References:[1]Tillett W et al. Rheumatol (Oxford). 2012;51:275–83.[2]OECD (2020). Average wages (indicator). https://data.oecd.org/earnwage/average-wages.htmTable 1.Model-based estimates of LSmean changea (95% CI) from baseline in WPAI-PsA domains among pts working at baseline and with an observed change through W24 (N=474) and W52 (N=475)Change from baselineGUS 100mg Q4WGUS 100mg Q8WPBO(W0-24)PBO → GUS 100 mg Q4W (W24-52)VisitW24W52W24W52W24W52Absenteeism, N145145147147162163LSmean-3.4 (-6.5,-0.3)-4.1 (-6.8,-1.5)-3.0 (-6.0,0.1)-4.0 (-6.6,-1.3)-3.0 (-6.0, 0.04)-3.0 (-5.5,-0.4)Diff vs. PBO-0.4 (-4.6,3.8)-0.01 (-4.2, 4.2)Presenteeism, N145145147147162163LSmean-20.1 (-23.7,-16.6)-22.4 (-26.3,-18.6)-19.6 (-23.2,-16.1)-25.7 (-29.5,-21.8)-10.5 (-13.9,-7.0)-18.5 (-22.2,-14.7)Diff vs PBO-9.7* (-14.4,-5.0)-9.2* (-13.9,-4.5)Work productivity, N145145147147162163LSmean-20.1 (-24.1,-16.1)-22.6 (-26.8,-18.3)-19.2 (-23.1,-15.2)-25.9 (-30.0,-21.7)-10.6 (-14.4,-6.8)-17.6 (-21.7,-13.6)Diff vs PBO-9.5* (-14.8,-4.2)-8.6* (-13.9,-3.3)Non-work Activity, N242242246246245245LSmean-20.5 (-23.3,-17.7)-25.7 (-28.6,-22.7)-21.2 (-23.9,-18.4)-25.4 (-28.4,-22.5)-9.9 (-12.6,-7.1)-22.3 (-25.3,-19.4)Diff vs PBO-10.6* (-14.4,-6.8)-11.3* (-15.1,-7.5)CI=Confidence intervala. LSmean for each MI dataset is calculated based on an ANCOVA model for the change from baseline at W24/W52. The combined LSmean, which is the average of the LSmean, taken over all the MI datasets, is presented.*p<0.05Disclosure of Interests:Jeffrey Curtis Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, and UCB, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Steve Peterson Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Prasheen Agarwal Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Feifei Yang Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Chenglong Han Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, William Tillett Speakers bureau: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer Inc, and UCB, Consultant of: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer Inc, and UCB, Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, and UCB, Philip J Mease Speakers bureau: Boehringer Ingelheim and GlaxoSmithKline, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB, Proton Rahman Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Janssen and Novartis.
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Næss, V., R. T. Fosse, and T. Hofstad. "A possible inhibitory effect on the Shwartzman reaction in the rabbit caused by fentanyl-fluanisone tranquillization." Laboratory Animals 20, no. 4 (October 1, 1986): 304–6. http://dx.doi.org/10.1258/002367786780808776.
Full textAbstract:
Shwartzman's reaction was elicited in four Chinchilla rabbits. Two of the animals were tranquillized with fentanyl-fluanisone (Hypnorm®: Janssen Pharmaceuticals). There was a reduced response in the tranquillized rabbits while the untranquillized animals developed the typical dose-responsive skin reaction. Fentanyl-fluanisone tranquillization may interfere with the development of the Shwartzman reaction in Chinchilla rabbits.
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Coates, L. C., P. J. Mease, P. Helliwell, F. Van den Bosch, M. Trivedi, M. Alani, F. O. Le Brun, et al. "POS1049 EFFECT OF FILGOTINIB ON PASDAS: DRIVERS OF LOW AND VERY LOW ACTIVITY UP TO WEEK 100." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 801.2–802. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1721.
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Background:EQUATOR (NCT03101670) was a Phase 2, double-blind, randomised placebo (PBO)- controlled trial of the preferential Janus kinase 1 inhibitor filgotinib (FIL) for the treatment of psoriatic arthritis (PsA); EQUATOR2 (NCT03320876) is the open-label extension (OLE).Objectives:This post-hoc analysis assessed the effect of FIL on individual Psoriatic Arthritis Disease Activity Score (PASDAS) components; and the association between PASDAS disease activity (DA) levels and DA levels achieved for each PASDAS component and patient-reported outcomes (PROs) up to OLE Week (Wk) 100.Methods:In EQUATOR, patients with active moderate-to-severe PsA were randomised 1:1 to oral FIL 200 mg or PBO once daily (QD) for 16 wks.1 At Wk 16, patients could continue into the 304-wk OLE, in which all patients received FIL 200 mg QD. The proportions of patients with PASDAS of very low DA (VLDA; ≤1.9), LDA (>1.9–<3.2), moderate DA (MoDA; ≥3.2–<5.4), and high DA (HDA; ≥5.4) at core Wk 16 and OLE Wk 52 and 100 were assessed. The proportion with improved PASDAS status vs baseline (BL) at OLE Wk 52 and 100 was calculated. Percent change from BL in PASDAS components and PROs were assessed at core Wk 16 and OLE Wk 52 and 100 by PASDAS status (VLDA, LDA, other). Multivariate logistic regression analyses performed cross-sectionally identified PASDAS components and PROs associated with not achieving VLDA or LDA at core Wk 16 and OLE Wk 52 and 100; all analyses were observed cases.Results:At OLE Wk 52, LDA and VLDA were achieved by 27.5% and 16.8% of randomised patients, respectively (44.3% combined). At OLE Wk 100, LDA and VLDA were achieved by 26.0% and 17.6% of patients (43.6% combined; Figure 1). Of patients with HDA at BL, 69% improved to MoDA/LDA/VLDA, <4% remained in HDA and 27% did not reach Wk 100; of those in MoDA at BL, 63% improved to VLDA/LDA, 11% remained stable, <4% worsened and 22% did not reach Wk 100. Patient Global Assessment of Disease Activity (PtGDA), Short Form-36 physical component scale (SF-36 PCS), Functional Assessment of Chronic Illness Therapy, and Health Assessment Questionnaire Disability Index were found to be important components/PRO measures in achieving VLDA vs LDA (Table 1). Logistic regression indicated that factors associated with not achieving LDA at Wk 52 were PtGDA (odds ratio [OR]: 1.20, 95% confidence interval [CI]: 1.07–1.35), physician GDA (PhGDA; OR: 1.58, 95% CI: 1.18–2.12), and SF-36 PCS (OR: 0.79, 95% CI: 0.67–0.95); PtGDA was associated with not achieving VLDA (OR: 1.30, 95% CI: 1.15–1.47).Conclusion:The proportion of patients achieving PASDAS VLDA or LDA increased over time and remained stable between OLE Wk 52 and 100. Important factors in determining whether VLDA/LDA was met were PtGDA, PhGDA, and SF-36 PCS, although the low patient numbers is a limitation.References:[1]Mease P, et al. Lancet. 2018;392:2367–77Table 1.Mean % change from baseline in PASDAS components and PROs (observed cases)Core Wk 16 (FIL + PBO groups combined)n=122OLE Wk 52n=110OLE Wk 100n=97VLDAn=8(7%)LDAn=22(18%)Othersn=92(75%)VLDAn=22(20%)LDAn=36(33%)Othersn=52(47%)VLDA n=23(24%)LDAn=34(35%)Othersn=40(41%)PhGDA−93−75−44−94−82−56−96−84−54PtGDA−87−69−13−86−58−24−90−57−13Tender joint count 68−94−80−42−99−84−64−98−87−61Swollen joint count 66−99−80−64−99−96−78−99−94−80LEI−100−86−32−96−100−78−100−99−78Dactylitis−100−100−73−100−100−97−100−100−98C-reactive protein−66−2217138*−32−25−12−1324SF-36 PCS53261133239472316FACIT1195032975134994636HAQ-DI−84−68−18−85−51−18−88−45−19PASI−84−66−29−54−59−56−49−76−42Components or PRO measures in bold are those for which numerical differences between VLDA and LDA are greatest across timepoints*Due to outlier (3784)FACIT, Functional Assessment of Chronic Illness Therapy; HAQ-DI, Health Assessment Questionnaire Disability Index; LEI, Leeds Enthesitis Index; PASI, Psoriasis Area Severity Index; PhGDA, Physician Global Assessment of Disease Activity; PtGDA, Patient Global Assessment of Disease Activity; SF-36 PCS, Short Form-36 physical component summary; (V)LDA, (very) low disease activityAcknowledgements:EQUATOR and EQUATOR2 were sponsored by Galapagos NV Mechelen, Belgium) and co-funded by Galapagos NV and Gilead Sciences, Inc (Foster City, CA, USA). Benjamin Pett and his team, employees of Galapagos, provided assistance with statistical analyses. Medical writing/editorial support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), and was funded by Galapagos NV.Disclosure of Interests:Laura C Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Gilead, Janssen, Medac, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Novartis, and Pfizer, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer, SUN, and UCB, Philip Helliwell Paid instructor for: Janssen, Novartis, and Pfizer, Consultant of: Eli Lilly, Filip van den Bosch Consultant of: AbbVie, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Merck, and UCB, Mona Trivedi Shareholder of: Gilead Sciences, Amgen, Employee of: Gilead Sciences, Muhsen Alani Shareholder of: Gilead Sciences, Employee of: Gilead Sciences, Franck Olivier Le Brun Shareholder of: Galapagos, Employee of: Galapagos, Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Lien Gheyle Shareholder of: Galapagos, Employee of: Galapagos, Emilia Gvozdenovic Employee of: Galapagos, Dafna D Gladman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB., Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB.
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Curtis, J., I. Mcinnes, D. D. Gladman, F. Yang, S. Peterson, P. Agarwal, A. Kollmeier, et al. "POS1028 PATIENT CHARACTERISTICS & CLINICAL FEATURES ASSOCIATE WITH HEALTH-RELATED QUALITY OF LIFE IN BIO-NAÏVE PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS THROUGH WEEK 24 OF THE DISCOVER-2 STUDY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 784–85. http://dx.doi.org/10.1136/annrheumdis-2021-eular.432.
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Background:Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by peripheral arthritis, axial inflammation, dactylitis, enthesitis, & skin/nail psoriasis. Patients (pts) with PsA often experience reduced health-related quality of life (HRQoL) due to these features.Objectives:Using EuroQoL-5 dimension-5 level (EQ-5D-5L) questionnaire index & visual analog scale (EQ-VAS) scores, we assessed HRQoL in pts with PsA & its association with pt characteristics & clinical features of PsA, including fatigue.Methods:The Phase 3 DISCOVER-2 trial evaluated guselkumab (GUS), a human monoclonal antibody targeting the IL-23p19-subunit, in bio-naïve adults with active PsA (swollen joint count [SJC] ≥5, tender joint count [TJC] ≥5, C-reactive protein [CRP] ≥0.6 mg/dL) despite standard therapies.1 Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at Week 0 (W0), W4, then Q8W; or placebo (PBO). EQ-5D-5L index assesses mobility, self-care, usual activities, pain/discomfort, & anxiety/depression. EQ-VAS assesses pt health state. Spearman correlation testing was used to evaluate relationships between baseline (BL) pt characteristics & PsA clinical features & BL EQ-5D-5L index & EQ-VAS scores (Figure 1). Employing absolute observed scores at both W0 & W24, univariate linear regression was used to assess the association between EQ-5D-5L index & EQ-VAS scores & pt characteristics/PsA clinical features. Variables with p<0.20 in the univariate analysis were included in a multivariate analysis employing mixed-effect model for repeated measures (MMRM), controlling for all other variables; resulting p values <0.05 were considered statistically significant. Least-squares (LS) mean changes in EQ-5D-5L index & EQ-VAS were assessed at W24 using MMRM.Results:Among 738 pts, BL EQ-5D-5L index & EQ-VAS scores were moderately to strongly correlated (ie, ≥0.4) with BL pt-reported pain (0-10 VAS), physical function (Health Assessment Questionnaire-Disability Index [HAQ-DI]), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] scale), & 36-item Short Form Health Survey (SF-36) physical & mental component summary (PCS & MCS) scores & weakly correlated with other variables (Figure 1). Based on univariate analyses (p<0.20) & evaluation of collinearity between variables, attributes at W0 & W24 included in the multivariate models were age, sex, CRP, FACIT-F, pain, psoriasis area & severity index (PASI) score, TJC, SJC, enthesitis, & dactylitis. In the final model, CRP, FACIT-F, pain, PASI score, & the presence of dactylitis were significantly associated with EQ-5D-5L index & EQ-VAS scores. A higher TJC was significantly associated with a worse EQ-5D-5L index score. A higher SJC was significantly associated with a worse EQ-VAS score (Table 1). For reference, in the GUS Q4W (N=244), GUS Q8W (N=246), & PBO (N=244) groups, the LS mean changes from baseline at W24 were 0.12, 0.12, & 0.05, respectively, for EQ-5D-5L index & 18.1, 18.4, & 6.8, respectively, for EQ-VAS.Conclusion:Joint & skin symptoms, dactylitis, fatigue, pain, & elevated levels of CRP were significantly associated with reduced HRQoL (measured by EQ-5D-5L index & EQ-VAS) in bio-naïve pts with active PsA. Treatment of multiple PsA domains may help optimize HRQoL. Improvement across clinical domains1 & in HRQoL has been observed in GUS-treated pts with PsA.References:[1]Mease P, et al. Lancet 2020;395:1126-36.Table 1.Multivariate analysis of pt characteristics/clinical features & EQ-5D-5L index & EQ-VAS scores at W0 & W24ParameterEQ-5D-5L IndexEQ-VASEstimatep valueEstimatep valueAge (y)-0.00010.690.060.12Female-0.0030.531.110.20CRP (mg/dL)-0.005<0.001-0.510.007FACIT-F (0-52)0.007<0.0010.57<0.001Pain (0-10)-0.02<0.001-3.47<0.001PASI (0-72)-0.0010.03-0.17<0.001SJC (0-66)-0.0010.21-0.170.02TJC (0-68)-0.0010.04-0.040.41Dactylitis (Y/N)0.010.021.740.49Enthesitis (Y/N)-0.0040.33-0.980.22Disclosure of Interests:Jeffrey Curtis Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Eli Lilly, Janssen, Myriad, Pfizer, Regeneron, Roche, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Eli Lilly, Janssen, Myriad, Pfizer, Regeneron, Roche, and UCB, Iain McInnes Consultant of: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, and UCB, Dafna D Gladman Consultant of: Abbvie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB, Grant/research support from: Abbvie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB, Feifei Yang Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Steve Peterson Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Prasheen Agarwal Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Chenglong Han Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, William Tillett Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, MSD, Pfizer, and UCB, Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB, Proton Rahman Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Janssen and Novartis.
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Mateos, Maria, Maria Gavriatopoulou, Thierry Facon, Holger W. Auner, Xavier Leleu, Roman Hajek, Meletios A. Dimopoulos, et al. "Effect of Prior Treatment with Proteasome Inhibitors on the Efficacy and Safety of Once-Weekly Selinexor, Bortezomib, and Dexamethasone in Comparison with Twice-Weekly Bortezomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma: Subgroup Analysis from the Boston Study." Blood 136, Supplement 1 (November 5, 2020): 48–50. http://dx.doi.org/10.1182/blood-2020-138391.
Full textAbstract:
Introduction Selinexor is a first-in-class, oral, potent selective inhibitor of nuclear export (SINE) which blocks XPO1, forcing the nuclear retention and activation of tumor suppressor proteins, leading to cancer cell apoptosis. Selinexor has demonstrated antimyeloma activity in triple class refractory multiple myeloma (MM) [Chari et al. NEJM 2019]. Selinexor synergizes with proteasome inhibitors (PIs) in PI-sensitive and -resistant cell lines and produces high response rates in patients with PI refractory and non-refractory MM (Bahlis et al. Blood 2018). In the phase 3 BOSTON study, the combination of once weekly (QW) selinexor, QW bortezomib, and dexamethasone (SVd) in patients who had received 1-3 prior therapies led to a significantly longer (47%) median progression-free survival (PFS) of 13.93 vs 9.46 months, with a hazard ratio of 0.70 (P=0.0075) compared to standard twice weekly bortezomib and dexamethasone (Vd). In addition, SVd regimen produced higher response rates and deeper responses (ORR: 76.4% vs 62.3% and ≥CR 16.9% vs 10.2%) compared with Vd. The benefit with SVd was observed across all efficacy endpoints and was associated with lower incidence and severity of bortezomib-induced peripheral neuropathy. Here we analyzed the effect of prior PI therapy (bortezomib, carfilzomib, ixazomib) on the efficacy and safety of SVd compared with Vd. Methods BOSTON is an open-label, randomized phase 3 study in patients with MM comparing SVd (QW oral selinexor 100 mg, QW subcutaneous bortezomib 1.3 mg/m2, and BIW oral dexamethasone 20 mg), versus Vd (BIW bortezomib 1.3 mg/m2 and QIW dexamethasone 20 mg). Patients previously treated with a PI must have had at least a partial response (PR) to the PI and 6 months since the last PI regimen. The study primary end point was PFS. Here we report subgroup analysis of treatment outcomes based on prior PI treatment. Results Subgroups consisted of PI naïve patients (n=95; 24%) and patients with prior PI treatment (n=307; 76%). Both the subgroups and study arms were comparable for baseline patient demographic and disease characteristics. However, those with prior PI treatment more frequently had a previous stem cell transplant (38% vs 24%) or 3 lines of prior anti MM therapy (21% vs 13%). Median PFS was improved with SVd compared with Vd in both the PI naïve group (PFS not reached (NR) vs 9.7 months; HR 0.2585 [95% CI, 0.1116-0.5988]; P=0.0003) and in the PI treated group (11.7 vs 9.4 months; HR 0.7839 [95% CI, 0.5791-1.0612]; P=0.06). Other efficacy endpoints are shown in the table. Peripheral neuropathy ≥grade 2 (a secondary study endpoint) was less frequent in the SVd compared with the Vd arm (PI naïve: 25.5%, Vd 43.8%, P=0.0302; PI treated: SVd 19.6%, Vd 31.4%, P=0.0092). Adverse events of ≥grade 3 occurred in 71% of patients in the PI naïve group (SVd 77%, Vd 65%) and 74% of patients in the PI treated group (SVd 88%, Vd 60%). Thrombocytopenia was more frequent in patients in the SVd arms (PI naïve: SVd 32%, Vd 13%; PI treated: SVd 42%, Vd 19%) as was anemia (PI naïve: SVd 15%, Vd 6%; PI treated: SVd 16%, Vd 12%), and fatigue (PI naïve: SVd 15%, Vd 2%; PI treated: SVd 13%, Vd 1%). Conclusions The once-weekly SVd combination was associated with significant clinical benefit and reduced peripheral neuropathy as compared with standard twice-weekly Vd in patients with MM and 1-3 prior therapies, regardless of prior therapy with a PI. However, the benefits of SVd over Vd were more pronounced in patients who had never been treated with a PI (PFS HR 0.26), suggesting that selinexor could be an optimal partner for combining with weekly bortezomib as the first PI-containing MM regimen. Figure 1 Disclosures Mateos: Roche: Honoraria; Seattle Genetics: Honoraria; EDO Mundipharma: Honoraria; Adaptive Biotechnologies: Honoraria; GlaxoSmithKline: Honoraria; Abbvie: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Janssen: Honoraria. Gavriatopoulou:Amgen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Genesis Pharma: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Facon:Celgene, Janssen, Takeda, Amgen, Roche, Karyopharm, Oncopeptides, BMS, Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Auner:Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding. Leleu:AbbVie: Honoraria; GSK: Honoraria; Amgen: Honoraria; Novartis: Honoraria; Carsgen: Honoraria; Incyte: Honoraria; Merck: Honoraria; BMS-celgene: Honoraria; Janssen: Honoraria; Oncopeptide: Honoraria; Sanofi: Honoraria; Karyopharm: Honoraria. Hajek:Novartis: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Oncopeptides: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharma MAR: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Dimopoulos:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau. Delimpasi:GENESIS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Spicka:Celgene, Amgen, Janssen-Cilag, Takeda, Bristol-Myers Squibb, Novartis, Sanofi: Consultancy, Honoraria, Speakers Bureau. Kryachok:Janssen, Bayer, Karyopharm, MSD, Acerta, AvbbVie, Debiopharm: Research Funding; Takeda, Janssen: Consultancy; Takeda, MSD, AbbVie, Ro: Other: Travel, accommodations, expenses; Takeda, Janssen, Novartis, Roche, MSD, Bayer: Consultancy, Research Funding. Sinha:Dr Reddys Lab, Intas Pharmaceuticals, Karyopharm Therapeutics: Honoraria. Venner:Celgene, Amgen: Research Funding; Janssen, BMS/Celgene, Sanofi, Takeda, Amgen: Honoraria. Garg:Janssen, Takeda, Celgene, Novartis, Sanofi: Honoraria. Stevens:Amgen, MorphoSys: Consultancy. Quach:GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Research Funding; Glaxo Kline Smith: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Janssen Cilag: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria, Research Funding. Jagannath:BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy. Moreau:Amgen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Takeda: Honoraria; Janssen: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Honoraria. Levy:Karyopharm,Takeda, BMS: Consultancy, Honoraria, Speakers Bureau. Badros:Amgen: Consultancy; University of Maryland: Current Employment. Anderson:Karyopharm: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Bahlis:Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; BMS/Celgene and Janssen: Consultancy, Honoraria, Other: Travel, Accomodations, Research Funding; AbbVie: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria; GSK: Consultancy, Honoraria. Cavo:Jannsen, BMS, Celgene, Sanofi, GlaxoSmithKline, Takeda, Amgen, Oncopeptides, AbbVie, Karyopharm, Adaptive: Consultancy, Honoraria. Chai:Karyopharm Therapeutics Inc: Current Employment. Arazy:Karyopharm Therapeutics Inc.: Current Employment. Shah:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company. Shacham:Karyopharm: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents PCT/US12/048319, 499/2012, PI20102724, and 2012000928) . Kauffman:Karyopharm Therapeutics Inc: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Richardson:Celgene/BMS, Oncopeptides, Takeda, Karyopharm: Research Funding.
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Deodhar, A., X. Baraliakos, I. Mcinnes, K. De Vlam, L. Bessette, A. Maniccia, R. Lippe, et al. "POS0907 EFFECT OF UPADACITINIB ON REDUCING PAIN IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS AND INADEQUATE RESPONSE TO NONSTEROIDAL ANTI-INFLAMMATORY DRUGS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 712–13. http://dx.doi.org/10.1136/annrheumdis-2021-eular.604.
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Background:Pain is a debilitating symptom of ankylosing spondylitis (AS) and negatively impacts patient (pt) lives. Upadacitinib (UPA), a Janus kinase (JAK) inhibitor engineered for increased selectivity for JAK1 over JAK2, JAK3, and tyrosine kinase 2, 1 showed significant efficacy vs placebo (PBO) in the randomized phase 2/3 SELECT-AXIS 1 study in active AS.2Objectives:To evaluate the efficacy of UPA on multiple pain assessments through 64 weeks (wks).Methods:SELECT-AXIS 1 (NCT03178487) enrolled adults with active AS, who had an inadequate response, intolerance or contraindications to ≥2 NSAIDs, were biologic DMARD naive and met the modified New-York Criteria. Pts were randomized 1:1 to UPA 15 mg once daily (QD, n=93) or PBO (n=94) for 14 wks (Period 1), followed by open-label UPA 15 mg QD during 90-wk extension (Period 2); reported here are data through wk 64. Pain endpoints included the proportion of pts achieving ≥30%/≥50%/≥70% reduction in Pt’s Global Assessment (PGA) of pain on a 0–10 numeric rating scale (NRS), minimal clinically important difference (MCID, defined as ≥1 point reduction or ≥15% reduction from baseline [BL]) in PGA of pain, and much better improvement (MBI, defined as ≥2 point reduction and ≥33% reduction from BL) in PGA of pain. In addition, mean change from baseline in PGA of pain, BASDAI questions 2 (neck/back/hip pain) and 3 (peripheral pain/swelling), and pt’s assessment of back pain and nocturnal back pain NRS scores (NRS 0–10) were assessed. Non-responder imputation (binary endpoints) and mixed-effects model for repeated measurements (continuous endpoints) were used for missing data/dropouts in Period 1; as-observed analysis was used for Period 2.Results:A significantly higher proportion of pts receiving UPA vs PBO achieved reductions in all PGA of pain assessments as early as wk 2 that was sustained at all time points in Period 1; the only exception was ≥70% reduction in PGA of pain that was significant at wk 4 and sustained thereafter (Figure 1). For ≥30%/≥50%/≥70% reduction and MBI, the response rate increased over time with UPA; the difference for UPA vs PBO also continued to increase over time for ≥50% and ≥70% reduction endpoints. For MCID, an increase from BL to wk 2 was observed and plateaued thereafter. The mean change from BL in PGA of pain, BASDAI Q2, back pain, and nocturnal back pain NRS scores were significantly greater for UPA vs PBO at all time points in Period 1; BASDAI Q3 was significant at wk 8 and 14 (Figure 1). The effect of UPA on pain reduction was sustained through wk 64. PBO pts who switched to open-label UPA at wk 14 generally reached the same level of pain reduction as those initially randomized to UPA (Figure 1).Conclusion:In pts with active AS and an inadequate response/contraindication to NSAIDs, a greater proportion of patients treated with UPA achieved rapid, significant, and clinically meaningful reductions in pain vs PBO through 14 wks across multiple pain assessments. The reductions in pain were sustained over time, and pts who switched from PBO to UPA reached the same level of improvement as the continuous UPA group.References:[1]Parmentier JM, et al. BMC Rheumatology. 2018;2(23).[2]van der Heijde D, et al. Lancet. 2019;394(10214):2108-2117.Acknowledgements:AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by M Hovenden and J Matsuura of ICON plc and was funded by AbbVie.Disclosure of Interests:Atul Deodhar Speakers bureau: Novartis, Pfizer, AbbVie, Eli Lilly, UCB Pharma, GlaxoSmithKline, Consultant of: Novartis, Pfizer, AbbVie, Eli Lilly, UCB Pharma, GlaxoSmithKline, Grant/research support from: Novartis, Pfizer, AbbVie, Eli Lilly, UCB Pharma, GlaxoSmithKline, Xenofon Baraliakos Consultant of: Novartis, Pfizer AbbVie, Eli Lilly, UCB Pharma, Galapagos Janssen, Celgene and Amgen, Grant/research support from: Novartis, Pfizer AbbVie, Eli Lilly, UCB Pharma, Galapagos Janssen, Celgene and Amgen, Iain McInnes Consultant of: AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers, Celgene, Janssen, Leo, Lilly, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers, Celgene, Janssen, Leo, Lilly, Novartis, Pfizer, and UCB, Kurt de Vlam Speakers bureau: Celgene Eli Lilly, Galapagos, Novartis, and UCB, Consultant of: Celgene, Eli Lilly, Galapagos, Novartis, and UCB, Grant/research support from: Celgene and Galapagos, Louis Bessette Speakers bureau: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Celgene, Lilly, Novartis, and Sanofi, Consultant of: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Celgene, Lilly, Novartis, Sanofi, Gilead, Grant/research support from: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Celgene, Lilly, Novartis, Sanofi, and Gilead, anna maniccia Shareholder of: AbbVie, Employee of: AbbVie, Ralph Lippe Shareholder of: AbbVie, Employee of: AbbVie, Christopher Saffore Shareholder of: AbbVie, Employee of: AbbVie, Tianming Gao Shareholder of: AbbVie, Employee of: AbbVie, In-Ho Song Shareholder of: AbbVie, Employee of: AbbVie, Andrew Ostor Consultant of: AbbVie, BMS, Roche, Janssen, Lilly, Novartis, Pfizer, UCB, Gilead, and Paradigm
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Gladman, D. D., M. Starr, R. Ranza, A. M. Bravo Perdomo, M. Strauss, M. Shawi, C. Han, E. Rampakakis, A. Andrew Östör, and P. J. Mease. "AB1087 LONG-TERM EFFICACY OF GUSELKUMAB IN FATIGUE AND IDENTIFICATION OF EARLY TREATMENT TARGETS: POST HOC ANALYSIS THROUGH 2 YEARS OF A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY CONDUCTED IN BIOLOGIC-NAÏVE PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1765.1–1765. http://dx.doi.org/10.1136/annrheumdis-2023-eular.1918.
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BackgroundThe IL-23p19-subunit inhibitor guselkumab (GUS) demonstrated clinically meaningful improvements in fatigue through one year of treatment[1]independent of its effects on American College of Rheumatology 20% (ACR20) improvement criteria and Minimal Disease Activity (MDA) achievement[2].ObjectivesIn this post-hoc analysis, the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) scale was used to: (a) evaluate the long-term effect of GUS in maintaining or further improving fatigue between week (W) 52 and W100, and to (b) identify potential early (W8) predictors, in terms of fatigue, for improved long-term fatigue outcomes.MethodsDISCOVER-2 enrolled adult patients (pts) with active PsA (≥5 swollen and ≥5 tender joints and CRP ≥0.6 mg/dl) who were naïve to biologics/JAK inhibitors. Pts were randomized (1:1:1) and treated with GUS 100 mg every 4W (Q4W); GUS 100mg at W0, W4, then Q8W; or placebo (PBO→GUS Q4W; crossing over to GUS Q4W at W24). Pts with baseline (BL) fatigue levels lower than the normative value (FACIT-F score ≤43)[3]were included in these post hoc analyses (N=681). The proportions of pts with clinically meaningful improvement (≥4 points) from BL in FACIT-F and with normative FACIT-F levels between W52 and W100 were calculated using non-responder imputation (NRI) for missing data and compared over time within each treatment group with the McNemar test. Changes in FACIT-F over time were assessed with mixed models adjusting for time, treatment group, their interaction, and BL FACIT-F score. Receiver operating characteristics (ROC) analyses were conducted using Youden’s index to determine optimal cutoffs at W8 for predicting achievement of normative scores and clinically meaningful FACIT-F responses at W100.ResultsAt BL, the mean (SD) FACIT-F score was 28.3 (8.7) with similar levels across treatment groups. At W52, 66.1%, 69.6%, 68.0%, and 67.8% of pts in the PBO→GUS Q4W, GUS Q4W, GUS Q8W, and pooled GUS groups, respectively, achieved clinically meaningful improvements from BL in FACIT-F score; response rates were maintained through W100. Normative FACIT-F levels were achieved by 24.9%, 28.1%, 29.4% and 27.5% of pts in each treatment group, respectively, at W52, and by increasingly greater proportions of pts through W100. Significant improvements from BL in FACIT-F scores were observed at W52 (all nominal p<0.05), with further improvements seen from W52 to W100 across all GUS groups (Figure 1). ROC optimal cutoff in FACIT-F improvement from BL to W8 associated with a clinically meaningful improvement in FACIT-F at W100 was ≥2.0 (nominal p<0.0001); while for achieving normative FACIT-F levels at W100, the optimal cutoff in actual FACIT-F score at W8 was ≥39.5 (nominal p<0.0001).ConclusionThe clinically meaningful improvements in fatigue seen after 1 year of GUS treatment were further enhanced through 2 years, at which time nearly a third of GUS-treated pts reported normative FACIT-F levels. Early targets in FACIT-F levels achieved with GUS were identified to aid in guiding treatment decisions in routine clinical practice.References[1] Ritchlin CT et al. RMD Open. 2022 Mar;8(1);e002195.[2] Rahman P et al. Arthritis Res Ther. 2021 Jul 14;23(1):190.[3] Montan I et al. Value Health. 2018 Nov;21(11):1313-1321.Acknowledgements:NIL.Disclosure of InterestsDafna D Gladman Consultant of: AbbVie, Amgen, Eli Lilly, Janssen, Pfizer, UCB, BMS, Galapagos, Gilead, and Novartis, Grant/research support from: AbbVie, Amgen, Eli Lilly, Janssen, Pfizer, UCB, Michael Starr Speakers bureau: (Advisory boards or honorariums) AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, R Ranza Speakers bureau: AbbVie, Janssen, Novartis, Pfizer, Consultant of: AbbVie, Janssen, Novartis, Pfizer, Ana Maria Bravo Perdomo Shareholder of: Johnson & Johnson, Employee of: Janssen Latin America, Marcie Strauss Employee of: Medasource, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Chenglong Han Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, Andrew Andrew Östör Consultant of: AbbVie, BMS, Eli Lilly, Gilead, Janssen, Novartis, Paradigm, Pfizer, Roche, and UCB, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB.
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Ramiro, S., R. B. M. Landewé, D. Van der Heijde, A. Sepriano, O. Fitzgerald, M. Østergaard, J. Homik, et al. "POS0111 MORE METICULOUSLY FOLLOWING TREAT-TO-TARGET IN RA DOES NOT LEAD TO LESS RADIOGRAPHIC PROGRESSION: A LONGITUDINAL ANALYSIS IN BIODAM." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 279–81. http://dx.doi.org/10.1136/annrheumdis-2022-eular.2161.
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BackgroundA Treat-to-Target approach (T2T) is broadly considered to lead to better clinical outcomes and recommended in patients with RA. However, very few studies have analyzed the effect of T2T on radiographic progression, and any such studies have provided inconsistent results.ObjectivesTo investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice leads to lower radiographic progression in RA.MethodsPatients from the multicenter RA-BIODAM cohort with ≥2 consecutive visits with radiographs available were included. In RA-BIODAM patients were enrolled as they were initiating a new csDMARD/bDMARD treatment were followed-up with the intention to benchmark and intensify treatment. The primary outcome of this analysis was the change in Sharp-van der Heijde score (SvdH, 0-448), assessed every 6 months, using average scores from 2 readers (scores with known chronological order). Following a DAS44-T2T remission strategy, which was defined at each 3-month visit, was the main variable of interest. Patients were categorized based on the proportion of visits in which T2T was followed according to our definition: very low (≤40% of the visits, low (>40%, <62.5%), high (≥62.5%, ≤75%) and very high (>75%). Radiographic progression at 2 years was visualized across groups by cumulative probability plots. Per 3-month interval T2T could be followed zero, one or two times (in a total of 2 visits). Associations between the number of visits with T2T in an interval and radiographic progression, both in the same and in the subsequent 6-month interval, were analysed by generalised estimating equations, adjusted for age, gender, disease duration and country.ResultsIn total, 511 patients were included (mean (SD) age: 56 (13) years; 76% female). After 2 years, patients showed on average 2.2 (4.1) units progression (median:1 unit). Mean (SD) 2-year progression was not significantly different across categories of T2T: very low: 2.1 (2.7)-units; low: 2.8 (6.0); high: 2.4 (4.5), very high: 1.6 (2.2) (Figure 1). Meticulously following-up T2T in a 3-month interval neither reduced progression in the same 6-month interval (parameter estimates (for yes vs no): +0.15 units (95%CI: -0.04 to 0.33) for 2 vs 0 visits; and +0.08 units (-0.06;0.22) for 1 vs 0 visits) nor did it reduce progression in the subsequent 6-month interval (Table 1).Table 1.Effect of following DAS44-remission-T2T strategy on 6-month radiographic progression over 2 yearsChange in radiographic damage(regression coefficient (95% CI))N=506T2T during 3 months on radiographic progression in the same 6-month period 2 visits vs 0 followed0.15 (-0.04; 0.33) 1 visit vs 0 followed0.08 (-0.06; 0.22)T2T during 3 months on radiographic progression in the subsequent 6-month period 2 visits vs 0 followed-0.09 (-0.28; 0.10) 1 visit vs 0 followed-0.10 (-0.24; 0.05)Figure 1.Cumulative probability plot with 2-year radiographic progression according to the proportion of 3-monthly visits with T2T followedConclusionIn this daily practice cohort, more meticulously following T2T principles did not result in more reduction of radiographic progression than a somewhat more liberal attitude toward T2T. One possible interpretation of these results is that the intention to apply T2T already suffices and that a more stringent approach does not further improve outcome.AcknowledgementsBIODAM was financially supported by an unrestricted grant from AbbVieDisclosure of InterestsSofia Ramiro Speakers bureau: Eli Lilly, MSD, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB, Sanofi, Grant/research support from: AbbVie, Galapagos, Novartis, Pfizer, UCB, Robert B.M. Landewé Speakers bureau: AbbVie, BMS, Gilead, Galapagos, GSK,Janssen, Lilly, Novartis, Pfizer, UCB, Consultant of: AbbVie, BMS, Gilead, Galapagos, GSK,Janssen, Lilly, Novartis, Pfizer, UCBDr Landewé owns Rheumatology Consultancy BV, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB Pharma. Director of Imaging Rheumatology bv., Alexandre Sepriano Speakers bureau: Novartis, Consultant of: UCB, Oliver FitzGerald Speakers bureau: Biogen, Novartis, AbbVie, BMS, Pfizer, Grant/research support from: BMS, Novartis, UCB, Pfizer, Lilly, Janssen, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Orion, Pfizer, Roche and UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Abbvie, Amgen, BMS, Merck, Celgene and Novartis, Joanne Homik: None declared, Ori Elkayam Speakers bureau: Pfizer, Lilly, Novartis, Abbvie, BI, Janssen, Consultant of: Pfizer, Lilly, Novartis, Abbvie, BI, Janssen, Grant/research support from: Pfizer, Abbvie, Janssen, Carter Thorne Consultant of: Abbvie, Organon, Pfizer, Sandoz, Maggie Larché Speakers bureau: AbbVie, Actelion, Amgen, BMS, Boehringer-Ingelheim, Fresenius-Kabi, Gilead, Janssen, Mallinckrodt, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, Sobi, UCB, Grant/research support from: Abbvie, BMS, Gianfranco Ferraccioli Speakers bureau: SOBI, Consultant of: Abbivie, Marina Backhaus: None declared, Gilles Boire Speakers bureau: Abbvie Canada, BMS Canada, Lilly Canada, Janssen Canada, Merck Canada, Pfizer Canada, Viatris, Consultant of: Abbvie Canada, Amgen Canada, BMS Canada, Celgene, GileadSciences, Janssen Canada, Lilly Canada, Merck Canada, Mylan Canada, Novartis Canada, Pfizer Canada, Roche Canada, Samsung Bioepis, Sanofi Canada, Teva, Grant/research support from: Lilly Canada, BMS Canada, Pfizer, Sandoz Canada, UCB Canada, Merck Canada, Novartis Canada, Roche Canada, Bernard Combe Speakers bureau: Abbvie, BMS,Celltrion,Galapgos-Gilead, Janssen, Lilly, MERCK, Pfizer,Roche-Chugai, Consultant of: Abbvie, Celltrion,Galapgos-Gilead, Janssen, Lilly, MERCK, Roche-Chugai, Grant/research support from: Pfizer, Roche-chugai, Thierry Schaeverbeke: None declared, Alain Saraux Speakers bureau: Abbvie, Lilly, Nordic, Novartis, Pfizer, Roche-Chugai, Sanofi, UCB, Consultant of: Abbvie, Lilly, Nordic, Novartis, Pfizer, Roche-Chugai, UCB, Grant/research support from: Novartis, Fresenius, Lilly, Maxime Dougados Consultant of: Pfizer, AbbVie, UCB, Merck, Lilly, Novartis, BMS, Galapagos, Biogen, Roche, Grant/research support from: Pfizer, AbbVie, UCB, Merck, Lilly, Novartis, BMS, Galapagos, Biogen, Roche, Maurizio Rossini Speakers bureau: Amgen, Abbvie, BMS, Eli-Lilly, Galapagos,MSD, Novartis, Pfizer, Sandoz, Theramex, UCB, Marcello Govoni Speakers bureau: Abbvie, Pfizer, Galapagos, BMS, Eli-Lilly, Paid instructor for: Pfizer, Consultant of: Abbvie, BMS, Novartis, Astrazeneca, Pfizer, Luigi Sinigaglia: None declared, Alain Cantagrel Speakers bureau: Abbvie, Amgen, Biogen, BMS, Janssen, Lilly France, Médac, MSD France, Nordic-Pharma, Novartis, Pfizer, Sanofi Aventis, UCB, Consultant of: BMS, Janssen, Lilly France, MSD France, Sandoz, Grant/research support from: MSD France, Novartis, Pfizer, Cornelia Allaart: None declared, Cheryl Barnabe Speakers bureau: Sanofi Genzyme, Pfizer, Fresenius Kabi, Janssen, Consultant of: Gilead, Celltrion Healthcare, Clifton Bingham Consultant of: AbbVie, BMS, Eli Lilly, Janssen, Moderna, Pfizer, Sanofi, Grant/research support from: BMS, Dirkjan van Schaardenburg: None declared, Hilde Berner Hammer Speakers bureau: AbbVie, Novartis, Lilly, Rana Dadashova: None declared, Edna Hutchings: None declared, Joel Paschke: None declared, Walter P Maksymowych Speakers bureau: Abbvie, Janssen, Novartis, Pfizer, UCB, Consultant of: Abbvie, Boehringer Ingelheim, Celgene, Eli-Lilly, Galapagos, Novartis, Pfizer, UCB, Grant/research support from: Abbvie, Novartis, Pfizer
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Kreuter, M., F. Bonella, K. Kathrin, J. Henes, E. Siegert, G. Riemekasten, N. Blank, et al. "POS0834 LONG-TERM OUTCOME OF SSC ASSOCIATED ILD: IMPROVED SURVIVAL IN PPI TREATED PATIENTS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 670.2–671. http://dx.doi.org/10.1136/annrheumdis-2021-eular.878.
Full textAbstract:
Background:Gastroesophageal reflux disease (GERD) occurs frequently in patients with systemic sclerosis (SSc) and SSc-associated interstitial lung disease (SSc-ILD). PPI use has to been shown to improve survival in patients with idiopathic pulmonary fibrosis, whereas to date there are no data on the use of PPI in SSc-ILD.Objectives:This study was aimed to assess whether use of PPI is associated with progression of SSc-ILD and survival.Methods:We retrospectively analysed 1931 patients with SSc and SSc-ILD from the German Network for Systemic Sclerosis (DNSS) database (2003 onwards). Kaplan–Meier analysis compared overall survival (OS) and progression-free survival (PFS) in patients with vs. without GERD (SSc and SSc-ILD), and PPI vs. no PPI use (SSc-ILD only). Progression was defined as a decrease in either % predicted forced vital capacity ≥10% or single-breath diffusing capacity for carbon monoxide ≥15%, or death.Results:GERD was not associated with decreased OS or PFS in patients with either SSc or SSc-ILD. In patients with SSc-ILD, PPI use was associated with improved OS vs. no PPI use after 1 year (98.4% [95% confidence interval: 97.6–99.3]; n=760 vs. 90.8% [87.9–93.8]; n=290) and after 5 years (91.4% [89.2–93.8]; n=357 vs. 70.9% [65.2–77.1]; n=106; p<0.0001). PPI use was also associated with improved PFS vs. no PPI use after 1 year (95.9% [94.6–97.3]; n=745 vs. 86.4% [82.9–90.1]; n=278) and after 5 years (66.8% [63.0–70.8]; n=286 vs. 45.9% [39.6–53.2]; n=69; p<0.0001).Conclusion:GERD had no effect on survival in SSc or SSc-ILD. PPIs improved survival in patients with SSc-ILD; however, controlled, prospective trials are needed to confirm this finding.Disclosure of Interests:Michael Kreuter Speakers bureau: Boehringer, Consultant of: Boehringer, Grant/research support from: Boehringer, Francesco Bonella Speakers bureau: Boehringer, Roche, GSK, Consultant of: Boehringer, Roche, GSK, Grant/research support from: Boehringer, Kuhr Kathrin: None declared, Jörg Henes Speakers bureau: Abbvie, Boehringer, Chugai, Roche, Janssen, Novartis, SOBI, Pfizer and UCB, Consultant of: Boehringer, Celgene, Chugai, Roche, Janssen, Novartis, SOBI, Grant/research support from: Chugai, Roche, Janssen, Novartis, SOBI, Pfizer, Elise Siegert: None declared, Gabriela Riemekasten Speakers bureau: Novartis, Janssen, Roche, GSK, Boehringer, Consultant of: Janssen, Actelion, Boehringer, Norbert Blank Consultant of: Sobi, Novartis, Roche, UCB, MSD, Pfizer, Actelion, Abbvie, Boehringer, Grant/research support from: Novartis, Sobi, Christiane Pfeiffer: None declared, Ulf Müller-Ladner: None declared, Alexander Kreuter Speakers bureau: MSD, Boehringer, InfectoPharm, Paid instructor for: MSD, PETER KORSTEN Consultant of: Glaxo, Abbvie, Pfizer, BMS, Chugai, Sanofi, Lilly, Boehringer, Novartis, Grant/research support from: Glaxo, Aaron Juche: None declared, Marc Schmalzing Speakers bureau: Chugai Roche, Boehringer, Celgene, Medac, UCB, Paid instructor for: Novartis, Abbvie, Astra Zeneca, Chugai Roche, Janssen, Consultant of: Chugai Roche, Hexal Sandoz, Gilead, Abbvie, Janssen, Boehringer, Margitta Worm Speakers bureau: Boehringer, Ilona Jandova Speakers bureau: Boehringer, Novartis, Abbvie, Laura Susok Speakers bureau: MSD, Novartis, BMS, Sunpharma, Consultant of: MSD, Tim Schmeiser Consultant of: Abbvie, Boehringer, Novartis, UCB, Claudia Guenther Paid instructor for: Advisory Board Boehringer January 2020, Employee of: Novartis 2002-2005, Gernot Keyszer Consultant of: Boehringer, Jan Ehrchen Speakers bureau: Boehringer, Janssen, Chugai, Sobi, Employee of: Pfizer, Actelion (now Janssen), Andreas Ramming Speakers bureau: Boehringer, Gilead, Janssen, Pfizer, Roche, Consultant of: Boehringer, Pfizer, Grant/research support from: Novartis, Pfizer, Ina Kötter Speakers bureau: several companies, Consultant of: several companies, Grant/research support from: several companies, Hanns-Martin Lorenz Speakers bureau: Abbvie, Astra Zeneca, Actelion, Alexion Amgen, Bayer Vital, Baxter, Biogen, Boehringer, BMS, Celgene, Fresenius, Genzyme, GSK, Gilead, Hexal, Janssen, Lilly, Medac, MSD, Mundipharm, Mylan, Novartis, Octapharm, Pfizer, Roche Chugai, Sandoz, Sanofi, Shire SOBI, Thermo Fischer, UCB, Grant/research support from: basic research studies: Pfizer, Novartis, Abbvie, Gilead, Lilly, MSD, Roche Chugai, Pia Moinzadeh Speakers bureau: Boehringer, Actelion, Grant/research support from: Actelion, Nicolas Hunzelmann Speakers bureau: Boehringer Janssen, Roche, Sanofi, Consultant of: Boehringer
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Bahlis, Nizar J., Shambavi Richard, Darrell J. White, Sebastian Grosicki, Christine Chen, Sosana Delimpasi, Heather J. Sutherland, et al. "Effects of Cytogenetic Risk on Outcomes in Multiple Myeloma Treated with Selinexor, Bortezomib, and Dexamethasone (XVd)." Blood 138, Supplement 1 (November 5, 2021): 1634. http://dx.doi.org/10.1182/blood-2021-146324.
Full textAbstract:
Abstract Introduction: Patients with multiple myeloma (MM) have a high rate of relapse resulting in a need for multiple lines of therapy. In contrast to MM with standard risk cytogenetics (SR-Cyto), high-risk cytogenetics (HR-Cyto) in MM such as del(17p), t(4;14), t(14;16), and gain(1q) (≥3 copies), can result in shorter progression-free survival (PFS) and overall survival (OS) with less durable responses. Treatment regimens that can overcome the negative effect of HR-Cyto abnormalities are required to address this area of unmet medical need. Exportin 1 (XPO1), is overexpressed in many hematologic and solid tumor malignancies including MM, and exports tumor suppressor proteins from the nucleus to the cytoplasm, leading to their inactivation. Elevated levels of XPO1 are correlated with more aggressive MM and resistance to therapy and confers a poor prognosis. The potent oral XPO1 inhibitor, selinexor, has been approved as a triplet combination with bortezomib and dexamethasone for previously-treated MM. In the Phase 3 BOSTON study, treatment with XVd in patients with previously treated MM significantly prolonged median PFS and improved the overall response rate (ORR), with a trend towards a prolonged OS amongst all patients as well as those with HR cytogenetics. Methods: We performed post hoc analyses on patients with previously-treated MM from the XVd arm of the Phase 1b/2 study STOMP (NCT02343042) and the Phase 3 BOSTON (NCT03110562) study to determine the effects of cytogenetic abnormalities on outcomes. The HR-Cyto group included patients with at least one of the following cytogenetic abnormalities at initial diagnosis or screening: del(17p), t(4;14), t(14;16), or gain(1q) (≥3 copies). Efficacy was based on independent review committee. Results: A total of 106 patients with HR-Cyto were identified, including del(17p) (n=25), t(4;14) (n=25), t(14;16) (n=10), and gain(1q) (n=80). There were 131 patients classified as SR-Cyto including those with unknown cytogenetics. Baseline demographics were similar between groups with median age of 66 years old (range 40-87). Patients with HR-Cyto had a median PFS of 12.9 months and patients with SR-Cyto had a median PFS of 16.6 months; PFS on the BOSTON Vd control arm were 8.6 and 9.5 months with HR- and SR-Cyto, respectively. Of the individual abnormalities, a PFS of 13.2 and 13.9 months was observed in the t(4;14) and gain1q subgroups, respectively. Of the HR-Cyto subgroups with more than 10 patients, a similar median OS was observed in comparison to SR-Cyto and ranged from 20.4 months to not reached. The response of XVd treatment was maintained across HR-Cyto risk subgroups, with an ORR of 76.4% overall and the following values for subgroups: del(17p) (72.0%), t(4;14) (88.0%), and gain1q (73.8%). The ORR of the SR group was 69.5%. Of all patients that received XVd, there were 6 CRs (5.7%) and 32 VGPRs (30.2%) in the HR group and 9 CRs (6.9%) and 29 VGPRs (22.1%) in the SR group. The ORRs on the BOSTON Vd control arm were 57.7% and 64.7% for HR- and SR-Cyto, respectively. The rates of the most common treatment emergent adverse events (TEAEs) of any grade were similar across risk groups (HR- vs SR-Cyto): thrombocytopenia (65.1% vs. 54.2%), nausea (53.8% vs. 53.4%), fatigue (47.2% vs. 45.0%) decreased appetite (37.7% vs. 42.0%) and anemia (34.6% vs 40.5%). Rates of AEs of any grade peripheral neuropathy (PN) were 35.8% overall, 40.0% in del(17p), t(4;14) (40.0%), t(14;16) (30.0%), gain(1q) (38.8%), and 23.7% in the SR group. The rates of PN in the HR and SR groups of the XVd arm of the BOSTON and STOMP studies were 37.1% and 29.6% and 11.1% and 15.2%, respectively. The corresponding rates for Vd alone in the BOSTON study were 48.6% and 47.0%. Conclusions: Patients with MM with HR-Cyto treated with XVd demonstrated a comparable ORR and PFS, with a manageable safety profile compared to patients with SR-Cyto, supporting the use of XVd in patients with any cytogenetic profile. These results are consistent with the distinct and broad mechanism of action associated with XPO1 inhibition and the use of the agent in earlier lines of therapy. Further assessment of selinexor in combination with other therapies in patients with MM across the entire cytogenetic spectrum is warranted. Figure 1 Figure 1. Disclosures Bahlis: Sanofi: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria; Genentech: Consultancy; BMS/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria. Richard: Karyopharm, Janssen: Honoraria. White: Amgen, Antengene, BMS/Celgene, Forus, GSK, Janssen, Karyopharm, Sanofi, Takeda: Consultancy, Honoraria. Chen: Gilead: Research Funding; BMS, Janssen, Abbvie, Novartis, Gilead, AstraZeneca: Consultancy. Delimpasi: Amgen: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. Sutherland: Amgen: Consultancy; Janssen: Consultancy, Research Funding; GSK: Research Funding; Celgene: Consultancy; Karyopharm: Research Funding. Sebag: Janssen: Research Funding; Bristol Myers-Squibb: Consultancy, Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria. Gavriatopoulou: GSK: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Genesis: Honoraria; Sanofi: Honoraria; Karyopharm: Honoraria; Amgen: Honoraria. Lentzsch: Oncopeptides: Consultancy; Sanofi: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; Takeda: Consultancy; GSK: Consultancy; AbbVie: Consultancy; Celularity: Consultancy; Janssen: Consultancy; Caelum Biosciences: Consultancy, Current holder of individual stocks in a privately-held company; Ossium Health: Consultancy; Magenta Therapeutics: Current equity holder in publicly-traded company; Kadmon: Current equity holder in publicly-traded company. Chari: Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Research Funding; Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Secura Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Shattuck Labs: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millenium/Takeda: Consultancy, Research Funding; Pharmacyclics: Research Funding; Janssen Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kriachok: Takeda, Roche, Abbvie, Janssen, MSD, Pfizer: Honoraria, Speakers Bureau; Takeda, Roche, Abbivie, Janssen, MSD: Consultancy. Dimopoulos: BMS: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Beigene: Honoraria. Auner: Janssen: Speakers Bureau; Amgen: Research Funding; Takeda, Karyopharm: Other: Advisory role. Leleu: Bristol-Myers Squibb: Honoraria; Carsgen Therapeutics Ltd: Honoraria; Celgene: Honoraria; Gilead Sciences: Honoraria; Janssen-Cilag: Honoraria; Karyopharm Therapeutics: Honoraria; Merck: Honoraria; Mundipharma: Honoraria; Novartis: Honoraria; Oncopeptides: Honoraria; Pierre Fabre: Honoraria; Roche: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; AbbVie: Honoraria; Takeda: Honoraria, Other: Non-financial support. Usenko: Janssen: Consultancy, Honoraria, Other: Clinical Trials Investigator; AbbVie: Consultancy, Honoraria, Other: Clinical Trials Investigator; Pfizer: Consultancy, Honoraria; Acerta: Other: Clinical Trials Investigator; Ascentage: Other: Clinical Trials Investigator; Celgene: Other: Clinical Trials Investigator; Il-Yang: Other: Clinical Trials Investigator; Karyopharm: Other: Clinical Trials Investigator; Oncopeptides: Other: Clinical Trials Investigator; Rigel: Other: Clinical Trials Investigator; Takeda: Other: Clinical Trials Investigator; UCB: Other: Clinical Trials Investigator. Hajek: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharma MAR: Consultancy, Honoraria; Novartis: Consultancy, Research Funding; AbbVie: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Venner: Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene: Research Funding; Amgen: Research Funding. Garg: Takeda Janssen Novartis Sanofi: Other: Travel Accommodations, Expenses; Amgen Janssen Novartis Sanofi Takeda: Honoraria; University Hospital Leicester: Current Employment. Quach: Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen/Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; CSL: Consultancy, Membership on an entity's Board of Directors or advisory committees. Jagannath: Karyopharm Therapeutics: Consultancy; Bristol Myers Squibb: Consultancy; Legend Biotech: Consultancy; Janssen Pharmaceuticals: Consultancy; Sanofi: Consultancy; Takeda: Consultancy. Moreau: Celgene BMS: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; Amgen: Honoraria; Oncopeptides: Honoraria. Levy: Takeda, Celgene, Seattle Genetics, AbbVie, Jazz Pharmaceuticals, Gilead Sciences, Bristol-Myers Squibb, Amgen, Spectrum Pharmaceuticals,Janssen.: Consultancy. Badros: J&J: Research Funding; Janssen: Research Funding; BMS: Research Funding; GlaxoSmithKline: Research Funding. Anderson: Celgene, BMS, Janssen, GSK, Karyopharm, Oncopeptides, Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Mateos: Oncopeptides: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sea-Gen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene - Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; Bluebird bio: Honoraria; AbbVie: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cavo: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Adaptive Biotechnologies: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Accommodations, Speakers Bureau; Novartis: Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau; Bristol-Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. DeCastro: Karyopharm: Current Employment, Current equity holder in publicly-traded company. Chai: Karyopharm: Current Employment. Van Domelen: Karyopharm: Current Employment, Current equity holder in publicly-traded company. Mishal: Karyopharm: Current Employment. Bentur: Karyopharm Therapeutics: Current Employment, Current equity holder in publicly-traded company. Shah: Karyopharm: Current Employment. Shacham: Karyopharm: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents PCT/US12/048319, 499/2012, PI20102724, and 2012000928) . Kauffman: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Richardson: Secura Bio: Consultancy; Sanofi: Consultancy; AstraZeneca: Consultancy; Oncopeptides: Consultancy, Research Funding; Janssen: Consultancy; Protocol Intelligence: Consultancy; Takeda: Consultancy, Research Funding; Regeneron: Consultancy; Celgene/BMS: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; AbbVie: Consultancy; Karyopharm: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding.
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Coates, L., J. Ramírez, D. Mcgonagle, S. Aydin, M. Zimmermann, F. Nantel, M. Shawi, E. Rampakakis, P. Nash, and P. J. Mease. "POS1540 EARLY SKIN AND EARLY ENTHESITIS RESPONSES IN PSORIATIC ARTHRITIS PATIENTS TREATED WITH GUSELKUMAB ASSOCIATE WITH LONG-TERM RESPONSE: POST HOC ANALYSIS THROUGH 2 YEARS OF A PHASE 3 STUDY." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1137.1–1137. http://dx.doi.org/10.1136/annrheumdis-2023-eular.2581.
Full textAbstract:
BackgroundGuselkumab (GUS), an IL-23p19 inhibitor, has demonstrated efficacy in psoriatic arthritis (PsA) across key Group for Research and Assessment of Psoriasis (PsO) and Psoriatic Arthritis (GRAPPA)-recommended domains[1,2]. Skin disease and enthesitis have been identified as disease manifestations with earlier response times than others[3].ObjectivesIn this analysis we: (a) Determined whether early skin and/or entheseal response predicts future response in other PsA domains; (b) Evaluated the trajectory for achieving skin/entheseal responses by 52 weeks (W) in patients (pts) without early responses.MethodsPts in the DISCOVER-1 and DISCOVER-2 (D1/2) studies were adults with active PsA despite standard therapies. D1 pts had ≥3 swollen and ≥3 tender joints (SJC/TJC) and C-reactive protein (CRP) ≥0.3 mg/dL; D2 pts had SJC ≥5, TJC ≥5, and CRP ≥0.6 mg/dL. 31% of D1 pts received 1-2 prior TNF inhibitors; D2 pts were biologic-naïve. Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then every 8 weeks (Q8W); or placebo. These post hoc analyses included only pooled GUS Q4W and Q8W pts (N=748). Early skin response was defined as PsO Area and Severity Index (PASI) score ≤1 at W16 or skin visual analogue scale (VAS) ≤15mm at W8 among pts with a baseline (BL) PASI score >1 and skin VAS >15mm (first assessment time for both); early entheseal response was defined as Leeds Enthesitis Index (LEI) score ≤1 at W8; and categories of early response were defined as skin VAS ≤15mm only vs LEI score ≤1 only vs combined skin VAS ≤15mm & LEI score ≤1 vs none at W8. Potential responses at W24 & W52 included achievement of minimal disease activity (MDA), Disease Activity in PsA (DAPSA) low disease activity (LDA) or remission, DAPSA50, and enthesitis/dactylitis resolution. Associations between early skin/entheseal response and W24/W52 response were assessed with crosstabulations and logistic regression.ResultsEarly skin response associated with greater odds of achieving W24 MDA, DAPSA LDA, DAPSA remission, and DAPSA50, but not enthesitis or dactylitis resolution (Figure 1). Early entheseal response associated with greater odds of achieving all W24 outcomes, including resolution of enthesitis or dactylitis, with the exception of DAPSA remission; DAPSA remission was achieved by a greater proportion of early responders, though the association was significant only at W52. In pts with both BL PsO and enthesitis, early responders in both domains were even more likely to subsequently demonstrate MDA, DAPSA LDA, DAPSA50, DAPSA remission only at W52, and dactylitis resolution than pts with individual responses. Among pts who did not achieve early responses, approximately half did so by W52.ConclusionEarly skin and entheseal responses predicted long-term clinical response, including disease remission. A synergistic effect was observed, in which pts with BL PsO and enthesitis exhibiting early response in both domains were more likely to achieve later clinical response. These results highlight the importance of early response in these two domains on the trajectory of long-term pt outcome.References[1]Deodhar A et al. Lancet. 2020;395(10230):1115-25[2]Mease PJ et al. Lancet. 2020;395(10230):1125-36[3]Coates LC et al. A893. EULAR 2022, DenmarkAcknowledgements:NIL.Disclosure of InterestsLaura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Julio Ramírez Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, and UCB, Consultant of: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, and UCB, Dennis McGonagle Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Sibel Aydin Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Miriam Zimmermann Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Francois Nantel Shareholder of: Johnson & Johnson, Consultant of: Janssen, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson & Johnson, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, Peter Nash Grant/research support from: AbbVie, Boehringher-Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, MSD, Novartis, Pfizer, Samsung, Sun Pharma, and UCB, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB.
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Curtis, J., A. Deodhar, E. Soriano, E. Rampakakis, M. Shawi, N. Shiff, M. Strauss, C. Han, W. Tillett, and D. D. Gladman. "AB1084 GUSELKUMAB PROVIDES RAPID CLINICALLY MEANINGFUL IMPROVEMENTS IN CLINICAL AND PATIENT REPORTED OUTCOMES AND SUSTAINED DISEASE CONTROL OF PSORIATIC ARTHRITIS." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1762–63. http://dx.doi.org/10.1136/annrheumdis-2023-eular.515.
Full textAbstract:
BackgroundThe Group for Research and Assessment of Psoriasis and PsA advocates addressing all aspects of disease, including optimizing functional status and improving health-related quality of life (HRQoL).[1]Guselkumab (GUS) has demonstrated robust efficacy across key PsA domains at week (W) 24, with effects sustained or further enhanced through 2 years.[2-4]Timing of clinically meaningful improvement in disease activity (DA), functional status, and HRQoL is of interest to PsA patients (pts) and providers.Objectives1) Evaluate effect of GUS on time to minimally clinically important improvements (MCII) in pt reported outcomes and composite measures of DA; 2) Assess association between W4/W8 MCII achievement and later disease control (W24/W52).MethodsThis post hoc analysis evaluated 1120 adults with active PsA despite standard therapies from DISCOVER-1 (D1) (swollen & tender joint counts [SJC/TJC] ≥3 each, CRP ≥0.3 mg/dL, 1-2 prior TNF inhibitors [TNFi] in 31% of pts) and D2 (SJC/TJC ≥5 each, CRP ≥0.6 mg/dL, biologic-naïve). Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or placebo (PBO)→GUS 100 mg Q4W at W24. Time to MCII in outcomes of interest, i.e., improvement in cDAPSA ≥5.7, Joint Visual Analogue Scale [VAS] ≥15mm, Pt Pain ≥15mm, HAQ-DI ≥0.35, PASDAS ≥0.8, PtGA ≥15mm, Skin VAS ≥15mm, FACIT-F ≥4, SF-36 PCS ≥5, was compared between GUS vs PBO with Cox regression adjusting for baseline (BL) levels of respective outcome, treatment group, prior TNFi use, and BL DMARD use. MCII achievement was determined using non-responder imputation and compared between GUS and PBO using logistic regression adjusting for the above covariates. The association between MCII achievement at W4/W8 and stringent clinical response at W24/W52 amongst GUS-treated pts was assessed with logistic regression adjusting for prior TNFi use and BL DMARD use.ResultsTime to achieve MCII in all studied outcomes was significantly shorter (hazard ratio range: 1.3-2.5; all p<0.01) for both GUS Q4W and Q8W vs PBO, including cDAPSA as a representative example (Figure 1), with curve separation occurring at the first timepoint assessed. MCII rates also were significantly higher with GUS vs PBO at the first timepoint assessed, i.e., W4 for cDAPSA, Joint VAS, Pt Pain, and HAQ-DI and W8 for PASDAS, PtGA, Skin VAS, FACIT-F, and SF-36 PCS (Table 1).W4 achievement of MCII in cDAPSA, Joint VAS, Pt Pain, and HAQ-DI was associated with greater odds of achieving future disease control, defined as ACR50, ACR70, cDAPSA ≤13, PASDAS ≤3.2, and MDA, at W24 (odds ratio [OR] range: 1.5-3.6) and W52 (OR: 1.2-2.4). W8 achievement of MCII in all studied outcomes was also associated with greater odds of achieving disease control at W24 (OR: 1.4-17.2) and W52 (OR: 1.2-5.4).ConclusionIn pts with active PsA, treatment with GUS was associated with more rapid MCII in both clinical and pt reported outcomes compared with PBO. As early as W4, achievement of MCII vs non-achievement in each studied outcome, particularly PASDAS and cDAPSA, was associated with greater odds of longer-term stringent DA control. Findings highlight the impact of these rapid improvements with GUS - as early as W4 - on the trajectory of long-term pt outcomes.References[1]Coates LC, et al.Nat Rev Rheumatol2022;18:465[2]Deodhar A, et al.Lancet2020;395:1115[3]Mease PJ, et al.Lancet2020;395:1126[4]McInnes IB, et al.Arthritis Rheumatol2022;74:475Table 1.Proportions of Pts Achieving MCIIEndpoint with MCIIWeekGUS Q4WGUS Q8WPBOcDAPSA4¥58.5%†57.9%†46.8%873.9%‡72.1%‡56.8%Joint VAS4¥31.9%†34.1%‡21.1%845.3%‡45.7%‡30.7%Pt Pain4¥27.8%†29.4%†18.9%844.7%‡44.1%‡28.1%HAQ-DI4¥33.9%†30.5%*22.7%841.7%‡42.6%‡27.6%PASDAS8¥68.4%‡64.9%‡44.0%PtGA8¥53.4%‡53.7%‡32.9%Skin VAS8¥64.0%‡62.1%‡35.2%FACIT-F8¥51.1%*53.1%†43.4%SF-36 PCS8¥43.2%†41.6%35.8%*nominal p <0.05;†p <0.01;‡p ≤0.0001 vs PBO.¥First time point assessed.Acknowledgements:NIL.Disclosure of InterestsJeffrey Curtis Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, CorEvitas, Eli Lilly and Company, Janssen, Myriad, Novartis, Pfizer, Sanofi, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, CorEvitas, Eli Lilly and Company, Janssen, Myriad, Novartis, Pfizer, Sanofi, and UCB, Atul Deodhar Speakers bureau: Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, and UCB, Enrique Soriano Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Janssen, Novartis, and Roche, Grant/research support from: AbbVie, Janssen, Novartis, Pfizer, Roche, and UCB, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, May Shawi Shareholder of: Johnson & Johnson, Employee of: Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson & Johnson, Natalie Shiff Shareholder of: AbbVie, Gilead, Iovance, Jazz Pharmaceuticals, Johnson & Johnson, Novavax, and Viatris, Employee of: Janssen Scientific Affairs, LLC, a subsidiary of Johnson & Johnson, Marcie Strauss Consultant of: Janssen Scientific Affairs, LLC, Employee of: MEDASOURCE, Chenglong Han Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC of Johnson & Johnson, William Tillett Speakers bureau: Abbvie, Amgen, Eli-Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Consultant of: Abbvie, Amgen, Eli-Lilly, Janssen, MSD, Novartis, Ono-Pharma, Pfizer, and UCB, Grant/research support from: Abbvie, Amgen, Eli-Lilly, Janssen, Pfizer and UCB, Dafna D Gladman Consultant of: Abbvie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB, Grant/research support from: Abbvie, Amgen, Eli Lilly, Janssen, Pfizer, UCB.