Literatura académica sobre el tema "Philip Johnson Associates"

Background:Tildrakizumab (TIL), an anti–interleukin (IL)-23p19 monoclonal antibody, is approved in the US, EU, and Australia for treatment of moderate-to-severe plaque psoriasis.1A randomised, double-blind, placebo-controlled, multiple-dose, phase 2b study (NCT02980692) evaluating efficacy and safety of TIL for treatment of psoriatic arthritis (PsA) was recently completed.Objectives:To evaluate the effect of TIL in PsA, using the DAS28-CRP responses up to week (W)52.Methods:Patients (pts) ≥18 years old with PsA2and ≥3 tender and ≥3 swollen joints were randomised 1:1:1:1:1 to receive TIL (200 mg once every 4 weeks [Q4W], 200 mg every 12 weeks [Q12W], 100 mg Q12W, or 20 mg Q12W) or placebo (PBO Q4W) to W24. Thereafter, PBO Q4W and TIL 20 mg Q12W arms crossed over to TIL 200 mg Q12W to W52. DAS28-CRP was shown to be reliable in PsA studies,3and pts achieving scores <3.2 satisfied responder criteria. Adverse events (AEs), including treatment-emergent AEs (TEAEs) and serious AEs (SAEs), were monitored throughout the study.Results:Overall, 391/500 pts screened met the inclusion criteria; 55% were female with a mean age of 48.8 years. At baseline, disease characteristics were generally consistent across treatment arms (Table).At W24, DAS28-CRP response rates increased across all TIL treatment arms relative to PBO (Figure). After W24, response rates continued to increase and were sustained through W52, including in pts who switched from PBO to TIL.From W0–W24/W25–W52, 50.4%/39.9% and 2.3%/1.0% of pts experienced a TEAE and SAE, respectively. There were no reports of candidiasis, inflammatory bowel disease, major adverse cardiac events or elevated liver enzymes. From W0–W24, 1 pt (0.3%) had urinary tract infection (TIL 100 mg Q12W). From W25–W52, 1 pt (0.3%) had an intraductal proliferative breast lesion (TIL 20→200 mg Q12W). One pt (0.3%) discontinued before 24 weeks due to hypertension. No deaths were reported.Table.Baseline disease characteristics related to DAS28-CRPTIL 200 mg Q4Wn = 78TIL 200 mg Q12Wn = 79TIL 100 mg Q12Wn = 77TIL 20→200 mg Q12Wn = 78PBO→TIL 200 mg Q12Wn = 79hsCRP, mg/L7.8 ± 18.610.5 ± 14.410.6 ± 20.010.7 ± 14.013.0 ± 20.8ESR, mm/h*22.8 ± 18.922.5 ± 19.824.7 ± 19.827.2 ± 20.726.9 ± 20.5Swollen joint count (66)10.4 ± 7.410.0 ± 8.011.0 ± 8.29.4 ± 6.411.8 ± 9.8Tender joint count (68)16.6 ± 11.919.5 ± 13.921.3 ± 14.819.0 ± 13.019.7 ± 14.7PtGA57.8 ± 18.361.1 ± 20.760.3 ± 20.261.9 ± 17.465.2 ± 18.1Data are reported as mean ± standard deviation unless otherwise stated.*Total pts analysed (n) = 71, 69, 70, 68, 62, respectively.ESR, erythrocyte sedimentation rate; hsCRP, high-sensitivity C-Reactive Protein; PBO, placebo; PtGA, Patient Global Assessment; pts, patients; Q4W, every 4 weeks; Q12W, every 12 weeks; TIL tildrakizumab.Conclusion:Treatment with all doses of TIL increased the rate of DAS28-CRP responders in pts with active PsA and was well tolerated, suggesting a reduction in PsA-related disease activity for up to 52 weeks of treatment. Ongoing analyses will assess whether DAS28-CRP responses correlate with baseline clinical characteristics.References:[1]Reich K, et al.Lancet. 2017;390(10091):276−88.[2]Taylor W, et al.Arthritis Rheum. 2006; 54(8):2665−73.[3]Fransen J, et al.Ann Rheum Dis. 2004; 62:151.Disclosure of Interests:Saima Chohan Employee of: Partner/physician at Arizona Arthritis and Rheumatology Associates, Arthur Kavanaugh Grant/research support from: AbbVie, Amgen, Eli Lilly, Novartis, Janssen, Pfizer, Gilead, UCB, Consultant of: AbbVie, Amgen, Eli Lilly, Novartis, Janssen, Pfizer, Gilead, UCB, Vibeke Strand Consultant of: AbbVie, Amgen, Biogen, Celltrion, Consortium of Rheumatology Researchers of North America, Crescendo Bioscience, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi, UCB, Richard C Chou Consultant of: Sun Pharmaceutical Industries, Inc, Alan M Mendelsohn Shareholder of: Johnson and Johnson, Employee of: Sun Pharmaceutical Industries, Inc, Stephen Rozzo Employee of: Sun Pharmaceutical Industries, Inc, 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

BackgroundLupus nephritis (LN) is one of the most common severe clinical manifestations of systemic lupus erythematosus (SLE), occurring in 21%–48% of SLE patients.[1]The kidney is the major organ affected in SLE, with persistent inflammation leading to progressive loss of renal function and chronic kidney disease (CKD). The decline in kidney function leads to an accumulation of metabolic waste products normally cleared by the kidneys, known as uremic toxins. Uremic toxins negatively affect multiple organ systems, causing increased cardiovascular and kidney damage, among other effects.[2]Given the clear link to kidney function, uremic toxins may serve as biomarkers of kidney damage and of treatment response.Anifrolumab, a monoclonal antibody that targets the type I interferon (IFN) receptor subunit 1, is approved for moderate to severe SLE treatment[3]and intensified dosing is being evaluated in a phase 3 study for LN treatment.ObjectivesIn this study, we conducted unbiased metabolomic serum profiling to identify novel biomarkers of treatment response and provide insights into the mechanism of action of anifrolumab in LN.MethodsIn the 52-week phase 2 clinical trial TULIP-LN (NCT02547922), 147 patients with active LN were randomized 1:1:1 to receive intravenous anifrolumab every 4 weeks at standard SLE dosing (basic regimen [BR], 300 mg), intensified dosing (intensified regimen [IR], 900 mg for the first 3 doses, 300 mg thereafter), or placebo in addition to standard therapy.[4]Serum samples were obtained from 140 of these patients at baseline (BL) and Weeks 12, 24, and 52. Serum metabolites were analyzed using an unbiased liquid chromatography–mass spectrometry-based approach. Metabolites that were differentially modulated in the anifrolumab IR vs placebo group were identified using a mixed effects model evaluating the interaction of metabolite levels and treatment, adjusted for patients’ IFN gene signature (IFNGS) status (high/low) and 24-hour urine protein–creatinine ratio (UPCR >3 or ≤3). Relationships between BL metabolite level and clinical characteristics of kidney damage were assessed by Spearman’s correlation. Association of BL metabolite levels with complete renal response were evaluated by logistic regression, adjusted for IFNGS and UPCR status.ResultsOur unbiased metabolomic approach identified 2 metabolites significantly impacted by anifrolumab treatment compared with placebo (Figure 1). Cytosine (Cyt) and indoxyl sulfate (IS) levels were significantly reduced following anifrolumab IR treatment compared with placebo, while an intermediate, non-significant reduction was observed longitudinally with anifrolumab BR. At baseline, Cyt and IS serum levels were positively correlated with serum creatinine and negatively correlated with estimated glomerular filtration rate. Baseline IS levels were also associated with complete renal response at Week 52. Compared to the trend observed in nonresponders, IS levels in responders were reduced from BL to Week 52. A trend in reduction of multiple uremic toxins not limited to IS was detected in the anifrolumab-treated group.ConclusionIn patients with LN, anifrolumab treatment reduced levels of multiple circulating uremic toxins including IS, a known inducer of cardiovascular damage in CKD.[5]Together, correlations with kidney damage measures at baseline and reductions in IS levels in responders vs nonresponders at Week 52 suggest improvements in kidney function following anifrolumab treatment. Overall, our results contribute to a deeper understanding of how inhibition of type I IFN affects renal disease in LN.References[1] Wang H, et al.Arch Rheumatol.2017;33:17–25.[2] Rosner MH, et al.Clin J Am Soc Nephrol.2021;16:1918–28.[3] AstraZeneca. Saphnelo prescribing information. 2021.[4] Jayne D, et al.Ann Rheum Dis.2022;81:496–506.[5] Zoccali C, et al.Nat Rev Nephrol.2017;13:344–58.AcknowledgementsWriting assistance by Katey Glunt, PhD, of JK Associates Inc., part of Fishawack Health.This study was sponsored by AstraZeneca.Disclosure of InterestsDavid Jayne Shareholder of: Aurinia, Speakers bureau: GSK, CSL Vifor, Consultant of: AstraZeneca, Chemocentryx, CSL Vifor, GSK, Novartis, Roche, Takeda, Grant/research support from: GSK, Roche, Patrick Gavin Employee of: AstraZeneca, Erik Allman Shareholder of: Primarily AstraZeneca but others through various Exchange Traded Funds (ETFs), Employee of: Previously, Janssen/Johnson & Johnson. Currently, AstraZeneca, Cristina Di Poto Shareholder of: AstraZeneca, Employee of: AstraZeneca, Xiang Tian Shareholder of: AstraZeneca, Employee of: AstraZeneca, Sonja Hess Shareholder of: AstraZeneca, Employee of: AstraZeneca, Madhu Ramaswamy Shareholder of: GSK, Employee of: AstraZeneca (until Jan 2023), GSK (from Jan 2023), Mark Lazarus Consultant of: Paid consulting for Novartis and Sandoz over 2 years ago, Employee of: AstraZeneca, Philip Z Brohawn Shareholder of: AstraZeneca, Employee of: AstraZeneca, Daniel Muthas Shareholder of: AstraZeneca, Employee of: AstraZeneca, Adam Platt Shareholder of: AstraZeneca, Employee of: AstraZeneca, Hussein Al-Mossawi Shareholder of: AstraZeneca, UCB, GSK, Speakers bureau: Novartis, Pfizer, UCB, Consultant of: Novartis, UCB, AbbVie, Grant/research support from: UCB, Employee of: UCB (Previous), AstraZeneca (Current), Catharina Lindholm Shareholder of: AstraZeneca, Employee of: AstraZeneca, Nicola Ferrari Shareholder of: AstraZeneca, Employee of: AstraZeneca.

Abstract Background The pathogenesis of inflammatory bowel disease (IBD) which includes Crohn’s disease (CD) and ulcerative colitis (UC), is believed to involve activation of the intestinal immune system in response to the gut microbiome among genetically susceptible hosts. IBD has been historically regarded as a disease of developed nations, though in the past two decades there has been a reported shift in the epidemiological pattern of disease. High-income nations with known high prevalence of disease are seeing a stabilization of incident cases, while a rapid rise of incident IBD is being observed in developing nations. This suggests that environmental exposures may play a role in mediating the risk of developing IBD. The potential environmental determinants of IBD across various regions is vast, though medications have been increasingly recognized as one broad category of risk factors. Purpose Several medications have been considered to contribute to the etiology of IBD. This study assessed the association between medication use and risk of developing IBD using the Prospective Urban Rural Epidemiology (PURE) cohort. Method This was a prospective cohort study of 133,137 individuals between the ages of 20-80 from 24 countries. Country-specific validated questionnaires documented baseline and follow-up medication use. Participants were followed prospectively at least every 3 years. The main outcome was development of IBD, including CD and UC. Short-term (baseline but not follow-up use) and long-term use (baseline and subsequent follow-up use) was evaluated. Results are presented as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Result(s) During the median follow-up of 11.0 years [interquartile range (IQR) 9.2-12.2], we recorded 571 incident cases of IBD (143 CD and 428 UC). Higher risk of incident IBD was associated with baseline antibiotic use [aOR: 2.81 (95% CI: 1.67-4.73), p=0.0001] and hormonal medication use [aOR: 4.43 (95% CI: 1.78-11.01), p=0.001]. Among females, previous or current oral contraceptive use was also associated with IBD development [aOR: 2.17 (95% CI: 1.70-2.77), p=5.02E-10]. NSAID users were also observed to have increased risk of IBD [aOR: 1.80 (95% CI: 1.23-2.64), p=0.002], which was driven by long-term users [aOR: 5.58 (95% CI: 2.26-13.80), p&lt;0.001]. All significant results were consistent in direction for CD and UC with low heterogeneity. Conclusion(s) Antibiotics, hormonal medications, oral contraceptives, and long-term NSAID use were associated with increased odds of incident IBD after adjustment for covariates. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding below: Salim Yusuf is supported by the Heart & Stroke Foundation/Marion W. Burke Chair in Cardiovascular Disease. The PURE Study is an investigator-initiated study funded by the Population Health Research Institute, the Canadian Institutes of Health Research (CIHR), Heart and Stroke Foundation of Ontario, support from CIHR’s Strategy for Patient Oriented Research (SPOR) through the Ontario SPOR Support Unit, as well as the Ontario Ministry of Health and Long-Term Care and through unrestricted grants from several pharmaceutical companies, with major contributions from AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier, and GlaxoSmithkline, and additional contributions from Novartis and King Pharma and from various national or local organisations in participating countries; these include: Argentina: Fundacion ECLA; Bangladesh: Independent University, Bangladesh and Mitra and Associates; Brazil: Unilever Health Institute, Brazil; Canada: Public Health Agency of Canada and Champlain Cardiovascular Disease Prevention Network; Chile: Universidad de la Frontera; China: National Center for Cardiovascular Diseases; Colombia: Colciencias, grant number 6566-04-18062; India: Indian Council of Medical Research; Malaysia: Ministry of Science, Technology and Innovation of Malaysia, grant numbers 100 -IRDC/BIOTEK 16/6/21 (13/2007) and 07-05-IFN-BPH 010, Ministry of Higher Education of Malaysia grant number 600 -RMI/LRGS/5/3 (2/2011), Universiti Teknologi MARA, Universiti Kebangsaan Malaysia (UKM-Hejim-Komuniti-15-2010); occupied Palestinian territory: the UN Relief and Works Agency for Palestine Refugees in the Near East, occupied Palestinian territory; International Development Research Centre, Canada; Philippines: Philippine Council for Health Research & Development; Poland: Polish Ministry of Science and Higher Education grant number 290/W-PURE/2008/0, Wroclaw Medical University; Saudi Arabia: the Deanship of Scientific Research at King Saud University, Riyadh, Saudi Arabia (research group number RG -1436-013); South Africa: the North-West University, SANPAD (SA and Netherlands Programme for Alternative Development), National Research Foundation, Medical Research Council of SA, The SA Sugar Association (SASA), Faculty of Community and Health Sciences (UWC); Sweden: grants from the Swedish state under the Agreement concerning research and education of doctors; the Swedish Heart and Lung Foundation; the Swedish Research Council; the Swedish Council for Health, Working Life and Welfare, King Gustaf V’s and Queen Victoria Freemasons Foundation, AFA Insurance, Swedish Council for Working Life and Social Research, Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, grant from the Swedish State under the Läkar Utbildnings Avtalet agreement, and grant from the Västra Götaland Region; Turkey: Metabolic Syndrome Society, AstraZeneca, Turkey, Sanofi Aventis, Turkey; United Arab Emirates (UAE): Sheikh Hamdan Bin Rashid Al Maktoum Award For Medical Sciences and Dubai Health Authority, Dubai UAE. Disclosure of Interest C. Pray: None Declared, N. Narula Grant / Research support from: Neeraj Narula holds a McMaster University Department of Medicine Internal Career Award. Neeraj Narula has received honoraria from Janssen, Abbvie, Takeda, Pfizer, Merck, and Ferring, E. C. Wong: None Declared, J. K. Marshall Grant / Research support from: John K. Marshall has received honoraria from Janssen, AbbVie, Allergan, Bristol-Meyer-Squibb, Ferring, Janssen, Lilly, Lupin, Merck, Pfizer, Pharmascience, Roche, Shire, Takeda and Teva., S. Rangarajan: None Declared, S. Islam: None Declared, A. Bahonar: None Declared, K. F. Alhabib: None Declared, A. Kontsevaya: None Declared, F. Ariffin: None Declared, H. U. Co: None Declared, W. Al Sharief: None Declared, A. Szuba: None Declared, A. Wielgosz: None Declared, M. L. Diaz: None Declared, R. Yusuf: None Declared, L. Kruger: None Declared, B. Soman: None Declared, Y. Li: None Declared, C. Wang: None Declared, L. Yin: None Declared, M. Erkin: None Declared, F. Lanas: None Declared, K. Davletov: None Declared, A. Rosengren: None Declared, P. Lopez-Jaramillo: None Declared, R. Khatib: None Declared, A. Oguz: None Declared, R. Iqbal: None Declared, K. Yeates: None Declared, Á. Avezum: None Declared, W. Reinisch Consultant of: Speaker for Abbott Laboratories, Abbvie, Aesca, Aptalis, Astellas, Centocor, Celltrion, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Immundiagnostik, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka, PDL, Pharmacosmos, PLS Education, Schering-Plough, Shire, Takeda, Therakos, Vifor, Yakult, Consultant for Abbott Laboratories, Abbvie, Aesca, Algernon, Amgen, AM Pharma, AMT, AOP Orphan, Arena Pharmaceuticals, Astellas, Astra Zeneca, Avaxia, Roland Berger GmBH, Bioclinica, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Covance, Danone Austria, DSM, Elan, Eli Lilly, Ernest & Young, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, LivaNova, Mallinckrodt, Medahead, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nash Pharmaceuticals, Nestle, Nippon Kayaku, Novartis, Ocera, Omass, Otsuka, Parexel, PDL, Periconsulting, Pharmacosmos, Philip Morris Institute, Pfizer, Procter & Gamble, Prometheus, Protagonist, Provention, Robarts Clinical Trial, Sandoz, Schering-Plough, Second Genome, Seres Therapeutics, Setpointmedical, Sigmoid, Sublimity, Takeda, Therakos, Theravance, Tigenix, UCB, Vifor, Zealand, Zyngenia, and 4SC, Advisory board member for Abbott Laboratories, Abbvie, Aesca, Amgen, AM Pharma, Astellas, Astra Zeneca, Avaxia, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Danone Austria, DSM, Elan, Ferring, Galapagos, Genentech, Grünenthal, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestle, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Sandoz, Schering-Plough, Second Genome, Setpointmedical, Takeda, Therakos, Tigenix, UCB, Zealand, Zyngenia, and 4SC, P. Moayyedi: None Declared, S. Yusuf: None Declared

Background:DISCOVER 1 & 2 are phase 3 psoriatic arthritis (PsA) trials investigating guselkumab (GUS), an IL-23 inhibitor that specifically binds the IL-23p19 subunit. In both studies, GUS showed significant improvement vs placebo (PBO) through week (W) 24 in the PBO-controlled period.1,2Objectives:To present integrated safety results of DISC 1 & 2 through the PBO-controlled periods.Methods:Adult patients (pts) with active PsA despite standard therapy were enrolled. All pts were biologic-naïve, except ~30% in DISC 1 with previous exposure to 1-2 TNF inhibitors. Pts were randomized to SC GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or PBO. Adverse events (AEs) and lab results were analyzed from pooled data.Results:The rates of pts experiencing ≥1 AE, serious AE, infection, serious infection, and discontinuation due to an AE were similar between GUS and PBO (Table 1). There were 2 deaths, 3 malignancies, 2 Major Adverse Cardiac Events (MACE), and no opportunistic infections (treatment group not shown to prevent unblinding). Among the AEs reported by ≥5% pts in any group (Table 1), nasopharyngitis and elevated serum hepatic aminotransferases were more common with GUS vs PBO. Laboratory ALT and AST elevations were mostly mild, transient, and not associated with significant bilirubin elevation. There was a trend to decreased neutrophil count (mostly Grade 1, transient, and not associated with infection) with GUS vs PBO (Table 2). Low rates of injection-site reactions were seen with GUS vs PBO. Anti-drug antibody development was also low (Table 1).Table 1.Patient Reported AEs, n (%)GUS100 mgQ8WGUS100 mgQ4WPBON375373372≥1 AE182 (48.5)182 (48.8)176 (47.3)≥1 Serious AE7 (1.9)8 (2.1)12 (3.2)Discontinuation due to AE5 (1.3)8 (2.1)7 (1.9)≥1 Infection73 (19.5)80 (21.4)77 (20.7)≥1 Serious infection1 (0.3)3 (0.8)3 (0.8)≥1 Opportunistic Infection (including Candida)000Active Tuberculosis000≥1 Injection-site reaction5 (1.3)4 (1.1)1 (0.3)Anti-GUS antibody +, n/N (%)6/373 (1.6)9/371 (2.4)--AEs* reported by ≥5% of patients in any treatment groupNasopharyngitis26 (6.9)19 (5.1)17 (4.6)Upper respiratory tract infection13 (3.5)23 (6.2)17 (4.6)Increased ALT23 (6.1)28 (7.5)14 (3.8)Increased AST23 (6.1)14 (3.8)9 (2.4)*Medical Dictionary for Regulatory Activities (MedDRA) preferred termTable 2.Lab Results*GUS100 mgQ8WGUS100 mgQ4WPBON373371370ALT Increased (%)Grade 128.235.030.121.12.71.43-40.81.10.8Neutrophil Count Decreased (%)Grade 15.65.93.221.61.60.83-400.30.3*NCI toxicity gradeALT=Alanine aminotransferaseConclusion:GUS was safe and well tolerated through the PBO-controlled period in 2 randomized, phase 3 trials of patients with active PsA. There were no meaningful safety differences between the Q8W and Q4W groups, no significant safety issues identified when comparing GUS to PBO, and no safety signals with regards to infections, malignancy, and MACE. The safety profile of GUS Q4W and Q8W in PsA pts was generally consistent with that in the Phase 3 trials of GUS Q8W for psoriasis.3,4References:[1]Deodhar et al. ACR 2019 (#807). Arth Rheum 2019;71 S10:1386[2]Mease et al. ACR 2019 (#L13). Arth Rheum 2019;71 S10:5247[3]Blauvelt et al. J Am Acad Derm 2017;76:405[4]Reich et al. J Am Acad Derm 2017;76:418Acknowledgments:NoneDisclosure of Interests: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, Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Philip Helliwell: None declared, Wolf-Henning Boehncke Grant/research support from: Janssen Research & Development, LLC, Consultant of: Janssen, 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, Alice B Gottlieb Grant/research support from:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Consultant of:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Speakers bureau:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Shelly Kafka Employee of: Janssen Scientific Affairs, 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, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Prasheen Agarwal Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Bei Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Paraneedharan Ramachandran Employee of: Janssen Research & Development, LLC, 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

BackgroundFatigue, one of the top 3 patient (pt)-reported symptoms of psoriatic arthritis (PsA) and a recent PsA outcome domain,1 causes impaired health-related quality-of-life, diminished productivity, and disability.1-3 Although the origins of fatigue are multifactorial, inflammation is hypothesized to play an important role.4 In pts with active PsA, treatment with guselkumab (GUS) led to clinically meaningful and sustained improvements in fatigue through 1 year in DISCOVER-1 (D1) and DISCOVER-2 (D2).5ObjectivesTo identify 1) factors associated with fatigue and 2) factors associated with change in fatigue among pts with PsA treated with GUS.MethodsIn the Phase 3 D1 (N=381, biologic-naïve and tumor necrosis factor inhibitor-experienced) and D2 (N=739, biologic-naïve) studies, pts with active PsA despite standard therapies and/or biologic disease-modifying antirheumatic drugs were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or placebo (PBO) with crossover to GUS 100 mg Q4W at W24. The pt-reported Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale measured fatigue (scored 0-52). In these post-hoc analyses of D1 and D2 pts, a principal component analysis (PCA) was performed using W0 data to identify the underlying baseline factors associated with fatigue. Additionally, linear regression analyses were performed to identify covariates associated with change in fatigue from W0 to W24.ResultsIn 1120 pts (mean age 47 yrs, mean disease duration 5.9 yrs, 48% female), mean FACIT-Fatigue scores at baseline ranged from 29.1 to 31.4 (vs 43.6 for the general US population).5 PCA showed that 62% of the variability in fatigue could be explained by 3 components (Figure 1). The first component, explaining 34% of variability in fatigue, largely comprised systemic disease activity and function measures such as pain, pt global assessment of disease activity (PtGDA), physician’s global assessment of disease activity, and Health Assessment Questionnaire-Disability Index (HAQ-DI). The second component, explaining 16% of variability, comprised joint manifestations including swollen joint count (SJC) and tender joint count (TJC). Skin involvement as assessed by Psoriasis Area and Severity Index (PASI) and systemic inflammation (C-reactive protein [CRP]) could explain 12% of the variability in fatigue (Figure 1 and Table 1). In a multivariate linear regression analysis, after adjusting for effects from other variables, improvement in CRP, physical function (HAQ-DI), PtGDA, and PASI score were significantly associated with fatigue improvement in GUS-treated pts at W24 (all p<0.001).Table 1.PCA of Pts With Active PsA in D1+D2 (N=1120; Pooled W0 data): Factor Loading Estimates by CovariatesComponent1 Systemic Disease Activity and FunctionComponent 2 Joint ManifestationsComponent 3 Skin Involvement and InflammationPsA disease duration, yr0.100.140.25PASI total score (0-72)0.220.230.74CRP, mg/dL0.36-0.130.55HAQ-DI score (0-3)0.73-0.09-0.19Pain (0-10 VAS)0.83-0.35-0.13PtGDA (0-10 VAS)0.82-0.36-0.16Physician global assessment of disease activity (0-10 VAS)0.65-0.180.23SJC (0-66)0.500.74-0.12TJC (0-68)0.540.70-0.18VAS=Visual Analog Scale.ConclusionAmong pts with PsA, measures of systemic disease activity and function, followed by joint manifestations, and skin involvement/inflammation accounted for 62% of the variability in fatigue. The large residual effect (38%) that was unexplained by the current model suggests the need for further research to identify additional factors (eg, distinct molecular pathways) contributing to the fatigue reported by PsA pts.References[1]Leung YY, et al. J Rheumatol (Suppl). 2020;96:46-9.[2]Gudu T, et al. Joint Bone Spine. 2016;83:439-43.[3]Husted JA, et al. Ann Rheum Dis. 2009;68:1553-8.[4]Krajewska-Włodarczyk M, et al. Reumatologia. 2017;55:125-30.[5]Rahman P, et al. Arthritis Res Ther. 2021;23:190.Disclosure of InterestsProton 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, GlaxoSmithKline, Janssen, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, and UCB, Arthur Kavanaugh Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Genentech, Janssen, Merck, Novartis, Pfizer 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, Yan Liu Shareholder of: 3 Johnson & Johnson, Employee of: Janssen Research & Development, LLC, 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.

Background:Guselkumab (GUS) is a human monoclonal antibody specific to the p19-subunit of interleukin-23. GUS significantly improved signs and symptoms of PsA through Week24 (Wk24), and improvements were maintained through Wk52 in the Phase 3 DISCOVER-11 and DISCOVER-22 studies.Objectives:Assess GUS efficacy through Wk52 in both studies utilizing composite indices.Methods:Adult patients (pts) enrolled had active PsA despite standard therapies. Pts in DISCOVER-1 had ≥3 swollen and ≥3 tender joints and C-reactive protein (CRP) ≥0.3 mg/dL; in 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 (Q4W); GUS 100 mg at Wk0, Wk4, then every 8 weeks (Q8W); or placebo (PBO); PBO pts crossed over to GUS 100 mg Q4W at Wk24. Composite endpoints pooled across the two studies were: Disease Activity Index for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Disease Activity Score (PASDAS), Minimal Disease Activity (MDA), and Very Low Disease Activity (VLDA). GUS vs PBO comparisons through Wk24 employed a Cochran-Mantel-Haenszel test with baseline stratification factors or Fisher’s exact test; no treatment group comparisons were performed beyond Wk24. P-values were not adjusted for multiplicity. From Wk24 -Wk52, pts with missing data were considered nonresponders (>90% of pts completed study treatment through Wk52).Results:In randomized and treated pts from DISCOVER-1 (N=381) and DISCOVER-2 (N=739), pooled baseline characteristics were generally well-balanced across treatment groups and reflected active disease. Differences in response rates between GUS Q4W or Q8W and PBO were seen as early as Wk8 and increased over time through Wk24. In pts continuing GUS Q4W or Q8W, respectively, post-Wk24 response rates associated with these composite indices continued to increase through Wk52, at which time they were 54.2% and 52.5% for DAPSA LDA, 45.3% and 41.9% for PASDAS LDA, 35.9% and 30.7% for MDA, 18.2% and 17.6% for DAPSA remission, and 13.1% and 14.4% for VLDA, with no discernable difference between the GUS Q4W and Q8W dosing regimens (Table 1 and Figure 1). After PBO pts crossed over to GUS Q4W at Wk24, response rates increased through Wk52.Conclusion:GUS 100 mg Q4W and Q8W provided robust and sustained benefits to pts with active PsA across multiple domains, indicating that GUS may provide an alternative treatment option for the diverse manifestations of PsA.References:[1]Ritchlin CR et al. RMD Open 2021; 1–11. doi: rmdopen-2020-001457[2]McInnes IB, et al. Arthritis Rheumatol 2020 Oct 11. doi: 10.1002/art.41553.Table 1.Pooled response rates for DISCOVER-1 and DISCOVER-2 randomized and treated patients.DISCOVER-1&2GUS Q4WGUS Q8WPBO -->GUS Q4W1Randomized and treated patients, n373375372PASDAS2LDAWk 2427.9%**30.1%**8.9%Wk 5245.3%41.9%36.8%MDA3Wk 2422.8%**24.3%**7.8%Wk 5235.9%30.7%28.2%DAPSA4RemissionWk 2410.2%**8.3%**2.2%Wk 5218.2%17.6%11.0%VLDA3Wk 246.4%**4.3%*1.3%Wk 5213.1%14.4%8.3%Data reported as proportions of patients, %. Unadjusted p values at Wk24 vs PBO: *p<0.05; **p<0.001.1 Pts randomized to PBO crossed over to GUS Q4W at Wk24.2 PASDAS is derived from Pt global assessment of arthritis and psoriasis (0-100), Physician global assessment (0-100), swollen joint count (0-66), tender joint count (0-68), CRP (mg/L), Leeds enthesitis index score, tender dactylitis count, and the 36-item Short-Form Health Survey Physical Component Summary score. PASDAS LDA ≤3.2.3 MDA is 5/7 criteria met; VLDA is 7/7 criteria met: tender joint count ≤1, swollen joint count ≤1, Psoriasis Activity and Severity Index ≤1, Pt assessment of pain ≤15 (0-100), Pt global assessment of disease activity ≤20 (0-100), Health Assessment Questionnaire-Disability Index score ≤0.5, Tender entheseal points ≤1.4 DAPSA Remission: score ≤4 (definition in Figure 1 legend).Disclosure of Interests:Laura C Coates Consultant of: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Novartis, Pfizer, Christopher T. Ritchlin Consultant of: Amgen, AbbVie, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, and UCB, Laure Gossec Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Biogen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, and UCB., Grant/research support from: Amgen, Eli Lilly, Galapagos, Janssen, Pfizer, Sandoz, and Sanofi, Philip Helliwell Consultant of: Galapagos, Janssen, and Novartis, Grant/research support from: AbbVie, Janssen, Pfizer, 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, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, 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, Chetan Karyekar Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Wim Noel Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Yusang Jiang Employee of: Cytel, Inc. providing statistical support (funded by Janssen), Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Yanli Wang Employee of: IQVIA providing statistical support (funded by Janssen), 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.

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.

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.

Background:Guselkumab (GUS), a novel monoclonal antibody that specifically binds to the p19-subunit of IL-23, demonstrated efficacy in the Ph 3 DISCOVER-1 (D1) & DISCOVER-2 (D2) trials of pts with active psoriatic arthritis (PsA).1,2Dactylitis & enthesitis, key PsA clinical manifestations, can be difficult to treat and may portend more significant disease burden.3,4Objectives:In pts with dactylitis or enthesitis at baseline, assess: 1) changes in symptoms over time and 2) relationships between improvements in dactylitis or enthesitis and other PsA domains.Methods:Adults with active PsA despite standard therapies were eligible for D1 & D2. Approx. 30% of D1 pts previously received 1-2 TNF inhibitors; D2 pts were biologic-naïve. Pts were randomized 1:1:1 to GUS 100mg Q4W; GUS 100mg at W0, W4, Q8W; or PBO. Independent assessors evaluated dactylitis (total score: 0-60) & enthesitis (Leeds Enthesitis Index [LEI]; total score 0-6). Dactylitis and enthesitis findings through W24 were prespecified to be pooled across D1 & D2. P-values are unadjusted. We assessed changes in dactylitis and LEI scores over time (ANCOVA); associations between dactylitis or enthesitis resolution and ACR/PASI responses at W24 (Chi-square); and correlations between dactylitis or LEI and HAQ-DI/SF-36 change scores at W24 (Spearman’s correlation). AEs through W24 were reported.1,2Results:At W0, 42% of pooled D1+D2 pts had dactylitis; 65% had enthesitis. GUS improved dactylitis and LEI scores vs PBO at W8, W16, W24. GUS vs PBO differences were significant for dactylitis changes at W16 & W24 and LEI changes at W8 (Q4W only), W16 & W24; no dose response was observed (Fig). Rates of dactylitis or enthesitis resolution by W24 were consistently significantly (p<0.001) associated with ACR20/50/70 and PASI75/90 response (Table). In GUS-treated pts at W24, significant correlations were observed between dactylitis change scores and PASI (p<0.001 Q4W; p=0.006 Q8W) and SF-36 MCS (p=0.038 Q4W; p=0.003 Q8W) changes, and between LEI and HAQ-DI change scores (p<0.001 Q4W; p=0.005 Q8W). No consistent correlations/associations were observed between dactylitis or LEI scores and other clinical outcomes.Conclusion:In PsA pts with dactylitis or enthesitis at W0, GUS improved dactylitis or LEI scores vs PBO by W8; treatment differences were significant at W16 & W24. Resolution of dactylitis or enthesitis was significantly associated with clinically meaningful improvements in PsA joint & skin symptoms. Improved dactylitis scores correlated with improved skin symptoms and mental health; improved LEI scores correlated with improved physical function.References:[1]Deodhar A (A#807),[2]Mease P (A#L13), Arthritis Rheumatol 2019;71(suppl 10);[3]DOI: 10.1186/s13075-017-1399-5;4DOI: 10.1016/j.semarthrit.2018.02.002Table.Pooled DISCOVER-1&2: associations between dactylitis/enthesitis resolution and joint/skin responseACR20ACR50ACR70PASI75aPASI90aDactylitis resolutionbN%pts%pts%ptsN%pts%pts Q4W37355*34*16*12178*55* Q8W37553*31*16*11680*65* PBO37226*12*5*11519*10*Enthesitis resolutionc Q4W24334*31*11*18782*63* Q8W23040*7*12*16277*62* PBO25514*13*5*18219*9** p < 0.001 (Chi-square)aIn pts with ≥3% BSA psoriasis & IGA ≥2 at W0bIn pts with D at W0cIn pts with E at W0Acknowledgments:NoneDisclosure of Interests:Dennis McGonagle Grant/research support from: Janssen Research & Development, LLC, 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, 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, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and 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, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shelly Kafka Employee of: Janssen Scientific Affairs, LLC, Chetan Karyekar Shareholder of: Johnson & Johnson, Consultant of: Janssen, Employee of: Janssen Global Services, LLC. Previously, Novartis, Bristol-Myers Squibb, and Abbott Labs., 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, 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, Prasheen Agarwal Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Bei Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, 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

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