Academic literature on the topic 'Myers, Kevin'

BackgroundDeucravacitinib is a first-in-class, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor approved in multiple countries for the treatment of adults with plaque psoriasis[1,2]. Deucravacitinib demonstrated efficacy across the primary endpoint and all key secondary endpoints in a phase 2 trial in patients with systemic lupus erythematosus (SLE)[3].ObjectivesHere, we describe 2 phase 3 trials currently underway to assess the efficacy and safety of deucravacitinib in patients with active SLE. These phase 3 trials have been designed to replicate the successful elements of the phase 2 trial, including its glucocorticoid-tapering strategy and rigorous management structure[3].MethodsIn these phase 3, randomized, double-blind, placebo-controlled, global trials (POETYK SLE-1 [NCT05617677], POETYK SLE-2 [NCT05620407]), adults (aged 18-75) with active SLE on background standard-of-care treatment will be randomized (1:1) to placebo or deucravacitinib for 52 weeks of double-blind treatment (Figure 1). Patients on glucocorticoids will be instructed to taper, unless significant disease activity is present, to a threshold dose level during the double-blind treatment period. At week 52, patients may choose to continue in a 104-week open-label extension phase, in which all patients receive deucravacitinib. Key eligibility criteria and study design are depicted below (Figure 1). The primary endpoint of SLE Responder Index (SRI[4]) and all secondary endpoints will be assessed at week 52 (Table 1). Safety and tolerability will be assessed throughout the trial.ResultsPlanned randomization in each trial includes 490 patients (245 per treatment group) in 27 countries across North and South America, Europe, and Asia-Pacific.ConclusionThe phase 3 POETYK SLE trials will further evaluate the efficacy and safety of deucravacitinib, an oral, selective, TYK2 inhibitor, in patients with active SLE.References[1]Armstrong A, et al.J Am Acad Dermatol.2022;S0190-9622(22)02256-3.[2]Strober B, et al.J Am Acad Dermatol.2022;S0190-9622(22)02643-3.[3]Morand E, et al.Arthritis Rheumatol.2022; Nov 11 (Epub ahead of print). doi: 10.1002/art.42391.Table 1.Primary and Secondary Endpoints Assessed at Week 52Primary Endpoint • Proportion of patients who achieve an SLE Responder Index (SRI[4]) responseSecondary Endpoints • Proportion of patients who achieve a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response • Proportion of patients with simultaneous achievement of SRI(4) and BICLA response (dual responders) • Proportion of patients who achieve a ≥ 50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-50) among patients with CLASI activity score ≥ 10 at baseline • Proportion of patients who achieve Lupus Low Disease Activity State (LLDAS) • Proportion of patients maintaining ≤ 7.5 mg/day glucocorticoid dose from weeks 24 to 52 • Proportion of patients who achieve a ≥ 50% reduction in active joints (Joint-Count 50) among patients with ≥ 6 active joints at baseline • Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scoreAcknowledgementsThis study was sponsored by Bristol Myers Squibb.Disclosure of InterestsCristina Arriens Speakers bureau: AstraZeneca, Aurinia, Bristol Myers Squibb, GlaxoSmithKline, Kezar, AstraZeneca and Aurinia, Grant/research support from: AstraZeneca and Bristol Myers Squibb, Anca Askanase Consultant of: Abbvie, Amgen, AstraZeneca, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech, GlaxoSmithKline, Idorsia, Janssen, Pfizer, and UCB, Richard Furie Consultant of: Bristol Myers Squibb, Grant/research support from: Bristol Myers Squibb, Eric F. Morand Consultant of: AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Genentech, Gilead, Novartis, and Servier, Grant/research support from: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Genentech, GlaxoSmithKline, Janssen, and UCB, Ronald van Vollenhoven Speakers bureau: AbbVie, Galapagos, Janssen, Pfizer, UCB, Consultant of: UCB, Pfizer, AstraZeneca, Biogen, Biotest, Celgene, Gilead, Servier, AbbVie, Galapagos, and Janssen, Grant/research support from: Bristol Myers Squibb, Eli Lilly, Pfizer, UCB, Roche, and GlaxoSmithKline, Kevin Connors Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Monica Davey Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Nikolay Delev Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Vaishali Shah Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Anna Stevens Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Thomas Wegman Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Coburn Hobar Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb.

BackgroundA previous real-world study has reported the characteristics, treatment patterns and clinical outcomes of patients with rheumatoid arthritis (RA) who received abatacept in UK clinical practice.1,2 However, many of the eligible population received abatacept monotherapy rather than as indicated. A subgroup analysis of patients treated with abatacept in combination with methotrexate (ABA + MTX) was therefore undertaken to explore the treatment effect in this specific patient population.ObjectivesPresent a subgroup analysis describing the clinical outcomes of patients with RA treated with ABA + MTX in UK real-world clinical practice.MethodsA multi-centre, retrospective observational study was undertaken in patients with RA treated with abatacept at any line of therapy between 1 January 2013 and 31 December 2017, across four UK centres. Data were collected from patient medical records from index date, defined as the date of first bDMARD initiation, to most recent RA clinic visit, death or end of study (31 December 2017). Clinical outcomes (disease activity and response to treatment) were measured using the 28-joint Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) and European League Against Rheumatism (EULAR) response criteria. Patients that received abatacept outside indication (i.e., without concomitant methotrexate) were retrospectively excluded from the analysis dataset. Statistical analyses for the ABA + MTX subgroup were repeated in line with the methodology previously reported.1,2ResultsThis subgroup analysis included 133 patients, of 213 patients included in the original study, with RA that received ABA + MTX (mean age 54.6 years, 77.4% female, 7.5 years mean duration of RA at index date). At index date, 64.8% of patients were positive for both anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF), where data were available. In total, 77.8% of patients were categorised with high disease activity at index, with mean DAS28-ESR of 6.2 (SD 1.1).Irrespective of line of treatment (LOT), patients tended to have a more favourable distribution of good/moderate/no EULAR response when receiving ABA + MTX (31.8%/34.1%/34.1%; n=44) compared with receipt of other bDMARDs (12.7%/36.4%/50.9%; n=55) at 6 months. Similarly, a favourable distribution of good/moderate/no EULAR response in favour of those receiving ABA + MTX compared with other bDMARDs was observed at 12 months (30.6%/41.7%/27.8% versus 20.0%/35.0%/45.0%, respectively).Patients receiving ABA + MTX remained on treatment for significantly longer than patients in receipt of other bDMARDs as first LOT (median time on treatment 53.4 vs 18.1 months; p<0.01). A similar trend was observed at second LOT, although differences were not statistically significant (median time on treatment 40.1 vs 19.7 months; p =0.08).ConclusionPatients with RA who received treatment with any bDMARDs, including ABA + MTX, experienced reduced disease activity. However, those receiving ABA + MTX persisted with treatment significantly longer than when receiving other bDMARDs.References[1]Choy, E. et al. Outcomes in rheumatoid arthritis patients treated with abatacept: a UK multi-centre observational study. BMC Rheumatology5, 3, doi:10.1186/s41927-020-00173-0 (2021).[2]Henning, S. et al. AB0295 CHANGE IN DISEASE ACTIVITY AND TREATMENT RESPONSE AFTER ABATACEPT TREATMENT FOR RHEUMATOID ARTHRITIS: REAL-WORLD EVIDENCE FROM THE UK. Annals of the Rheumatic Diseases79, 1446-1447, doi:10.1136/annrheumdis-2020-eular.1069 (2020).AcknowledgementsThis analysis was supported by Bristol-Myers Squibb.Disclosure of InterestsErnest Choy Speakers bureau: Abbvie, Amgen, Bristol Myer Squibbs, Chugai Pharma, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB, Consultant of: Abbvie, Amgen, Biogen, Biocon, Chugai Pharma, Eli Lilly, Gilead, Janssen, Merck Serono, Novartis, Pfizer, Regeneron, Roche, R-Pharm and Sanofi, Grant/research support from: Bio-Cancer, Biogen, Novartis, Pfizer, Roche, Sanofi and UCB, Sadie Henning Shareholder of: Bristol Myers Squibb, Employee of: Yes, Bristol Myers Squibb, Marie Brazil Shareholder of: Bristol Myers Squibb, Employee of: Currently an employee of Bristol Myers Squibb, Kevin Pollock Shareholder of: Yes - Bristol Myers Squibb, Speakers bureau: Yes - Merck Sharp & Dohme and Glaxo Smith Kline, Consultant of: Yes - Merck Sharp & Dohme, Employee of: Yes – currently employed by Bristol Myers Squibb, Lara Groves Grant/research support from: I am an employee of Health Economics and Outcomes Research Ltd., Cardiff, UK, who received fees from Bristol Myers Squibb in relation to this study, Daniel Sugrue Grant/research support from: I am an employee of Health Economics and Outcomes Research Ltd., Cardiff, UK, who received fees from Bristol Myers Squibb in relation to this study, John Houghton Grant/research support from: I am an employee of Health Economics and Outcomes Research Ltd., Cardiff, UK, who received fees from Bristol Myers Squibb in relation to this study

Background:Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that affects the axial skeleton and sacroiliac joints, and can be classified as ankylosing spondylitis (AS) or non-radiographic (nr)-axSpA.1A 2016 analysis estimated the US diagnostic prevalence of axSpA to be 0.2% and AS to be 0.1%.2Previous studies use disparate populations and diagnostic definitions;3,4it is therefore unclear how AS prevalence has changed over time.Objectives:To investigate the annual diagnostic prevalence of AS in US healthcare insurance claims databases.Methods:A retrospective, observational cohort study was conducted using 2006–2014 data from US Medicare Fee-for-Service Claims (5% random sample of all enrolled patients [pts]) and Truven MarketScan®. Eligible pts were ≥20 years (yrs) and had ≥6 months of continuous medical and pharmacy enrolment prior to diagnosis. Diagnoses used relevant International Classification of Disease, 9thversion (ICD-9) diagnosis codes: ICD-9 720.x [x=any number] for “AS and other inflammatory spondylopathies [SpA]” or 720.0 for “AS”. Two diagnosis definitions were used: Definition 1, ≥1 relevant ICD-9 code from hospital discharge or ≥2 from rheumatologist visit; Definition 2, ≥1 relevant ICD-9 code from hospital discharge or rheumatologist visit. Annual diagnostic prevalence of SpA/AS was calculated as “number of enrolled pts who met the definition of SpA/AS within each calendar yr and had full insurance coverage (medical and pharmacy)”, divided by “total number of pts with full insurance coverage in the same yr”. A primary analysis of SpA prevalence rates used Definitions 1 and 2, followed by a sensitivity analysis for AS prevalence rates using only Definition 2. All prevalence rates are shown per 10,000 pts enrolled.Results:The annual diagnostic prevalence of SpA appeared to increase from 2006–2014 (Table). Similarly, the sensitivity analysis showed the annual diagnostic prevalence of AS appeared to increase during the period from 2006 (Medicare: 2.87/10,000 pts [n=501,031]; MarketScan: 1.37/10,000 pts [n=17,562,637]) to 2014 (Medicare: 4.77/10,000 pts [n=1,046,107]; MarketScan: 2.14/10,000 pts [n=34,553,135];Figure).Conclusion:The apparent increase in diagnostic prevalence of SpA and AS during the period from 2006–‍2014 may be a consequence of increased awareness and availability of effective treatments. Furthermore, the 2009 Assessment of SpondyloArthritis international Society development of the axSpA classification criteria to include pts with both established AS and nr-axSpA may have accelerated this increase.5References:[1]Strand V. Mayo Clin Proc 2017;92:555–64;[2]Curtis J. Perm J 2016;20:15–151;[3]Reveille J. Arthritis Care Res (Hoboken) 2012;64:905–10;[4]Danve A. Clin Rheumatol 2019;38:625–34;[5]Rudwaleit M. Ann Rheum Dis 2009;68:777–83.Table.Prevalence of SpA by calendar year and data sourceMedicare (5% random sample)MarketScanCalendar yrTotal number of eligible ptsPrevalence/10,000 ptsTotal number of eligible ptsPrevalence/10,000 ptsDefinition 1Definition 2Definition 1Definition 22006501,0314.397.6217,562,6371.332.172007816,9705.258.7219,518,0661.472.372008825,4454.898.7828,603,5251.582.532009830,9675.229.2131,757,0691.903.092010844,5285.499.9031,126,1721.963.172011879,9966.3010.7138,295,1211.943.112012921,9946.1710.8840,320,4371.913.0420131,032,8276.7410.8233,826,0412.003.1920141,046,1076.5210.8534,553,1352.213.51Medicare data included a 5% random sample of all enrolled pts age ≥20 yrs. pts: patients; SpA: ankylosing spondylitis and other inflammatory spondylopathies; yr: year.Acknowledgments:This study was funded by UCB Pharma. Editorial services were provided by Costello Medical.Disclosure of Interests:Jeffrey Curtis Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corona, Crescendo, Genentech, Janssen, Pfizer, Roche and UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corona, Crescendo, Genentech, Janssen, Pfizer, Roche and UCB Pharma, Kevin Winthrop Grant/research support from: Bristol-Myers Squibb, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Pfizer Inc, Roche, UCB, Benjamin Chan: None declared, Sarah Siegel: None declared, Jeffrey Stark Employee of: UCB Pharma, Robert Suruki Employee of: UCB Pharma, Rhonda Bohn Consultant of: UCB Pharma, Fenglong Xie: None declared, Huifeng Yun Grant/research support from: Bristol-Myers Squibb and Pfizer, Lang Chen: None declared, 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

BackgroundTyrosine kinase 2 (TYK2) is an intracellular enzyme involved in IL-23 signaling that is important in the pathogenesis of immune-mediated diseases, including psoriasis, psoriatic arthritis, and systemic lupus erythematosus (SLE). Deucravacitinib is a first-in-class, oral, selective, allosteric TYK2 inhibitor approved in multiple countries for the treatment of adults with plaque psoriasis. Deucravacitinib uniquely binds to the TYK2 regulatory domain rather than the more conserved catalytic domain at which Janus kinase (JAK) 1/2/3 inhibitors bind. Deucravacitinib was efficacious compared with placebo in phase 2 trials in psoriatic arthritis and SLE.[1,2]Furthermore, deucravacitinib was significantly more efficacious than placebo or apremilast and was well tolerated in patients with moderate to severe plaque psoriasis, as observed in the phase 3 POETYK PSO-1 and PSO-2 trials.[3,4]Patients who completed the psoriasis trials could enroll in the ongoing open-label, 240-week long-term extension (LTE) trial.ObjectivesThis analysis examined whether changes occurred in blood laboratory parameters upon deucravacitinib treatment in the phase 3 POETYK PSO-1, PSO-2, and LTE trials and, if so, assessed how these compared with signature laboratory changes seen with JAK 1/2/3 inhibitors.MethodsPOETYK PSO-1 (NCT03624127) and PSO-2 (NCT03611751) were 52-week, double-blind trials that randomized patients with moderate to severe plaque psoriasis 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily. Patients receiving placebo switched to deucravacitinib at Week 16, and patients receiving apremilast who failed to achieve ≥50% reduction from baseline in Psoriasis Area and Severity Index (PASI 50; PSO-1) or ≥75% reduction from baseline in PASI (PASI 75; PSO-2) at Week 24 switched to deucravacitinib. At Week 52, all eligible patients enrolled in the LTE trial (NCT04036435) and received open-label deucravacitinib 6 mg once daily. Changes from baseline in hematologic parameters (lymphocytes, neutrophils, platelets, hemoglobin) and lipid and chemistry parameters (cholesterol, creatinine, CPK, ALT) known to be impacted by JAK 1/2/3 inhibitors were assessed through Week 100 (LTE at Week 48). CTCAE grade ≥3 laboratory abnormalities and treatment discontinuations due to laboratory abnormalities were also evaluated.ResultsPatients (n=1519) received ≥1 dose of deucravacitinib in PSO-1, PSO-2, and/or the LTE through the cutoff date of 1 October 2021. In total, 1179 (77.6%) and 584 (38.4%) patients had ≥52 and ≥104 weeks, respectively, of continuous deucravacitinib exposure at the cutoff date, and the median duration of exposure was 682.0 days (97 weeks). No trends for clinically meaningful changes from baseline were observed in any laboratory parameters from Weeks 0–52 in PSO-1 or in the LTE. Grade 3 or 4 abnormalities over 100 weeks of deucravacitinib treatment were rare; incidence rates were comparable with placebo and apremilast through Week 52, and no increases were seen in the LTE. Two patients discontinued deucravacitinib treatment due to laboratory abnormalities (1 lymphopenia, 1 abnormal hepatic function).ConclusionNo trends for clinically meaningful changes from baseline were observed with deucravacitinib treatment in hematologic, lipid, or chemistry parameters, including signature laboratory changes associated with JAK 1/2/3 inhibitors, for up to 100 weeks. Treatment discontinuations and grade 3 or 4 laboratory abnormalities were rare, consistent with those in the parent studies, and comparable to the incidence rates seen with placebo and apremilast. These results suggest that laboratory monitoring in patients with plaque psoriasis is not warranted with deucravacitinib treatment.References[5]Mease PJ, et al.Ann Rheum Dis. 2022;81:815-822.[6] Morand E, et al.Arthritis Rheumatol. 2022 Nov 11. doi: 10.1002/art.42391. Epub ahead of print.[7] Armstrong AW, et al.J Am Acad Dermatol.2023;88:29-39.[8] Strober B, et al.J Am Acad Dermatol.2023;88:40-51.AcknowledgementsThese clinical trials were sponsored by Bristol Myers Squibb.Disclosure of InterestsNeil J Korman Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Regeneron, and Sanofi Genzyme, Consultant of: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Principia, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Argenx, Bristol Myers Squibb, Celgene, Chemocentryx, Eli Lilly, Galderma, Kyowa Hakko Kirin, Leo Pharma, Menlo, Principia, Prothena, Rhizen, Syntimmune, Trevi, and XBiotech, Thierry Passeron Consultant of: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, Incyte, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi Genzyme, Sun Pharma, and UCB, Kenneth B Gordon Consultant of: Almirall, Amgen, Dermira, Leo Pharma, Pfizer, and Sun Pharma, Grant/research support from: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, and UCB, Yukari Okubo Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eisai, Eli Lilly, Janssen Pharma, Jimro, Kyowa Kirin, Leo Pharma, Maruho, Novartis, Pfizer, Sanofi, Sun Pharma, Taiho, Tanabe-Mitsubishi, Torii, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, and Sun Pharma, Grant/research support from: Eisai, Maruho, Shiseido, and Torii. AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, Maruho, Pfizer, Sun Pharma, and UCB, Jerry Bagel Speakers bureau: AbbVie, Celgene, Eli Lilly, Janssen Biotech, and Novartis, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Janssen Biotech, Novartis, Sun Pharma, and Valeant, Grant/research support from: AbbVie, Amgen, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, CorEvitas’ (Corrona) Psoriasis Registry, Dermavant, Dermira/UCB, Eli Lilly, Glenmark, Janssen Biotech, Kadmon, Leo Pharma, Lycera, Menlo Therapeutics, Novartis, Pfizer, Regeneron, Sun Pharma, Taro, and Valeant, Howard Sofen Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, Novartis, and Sun Pharma, Richard B. Warren Consultant of: AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, DiCE Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, and UNION, Grant/research support from: AbbVie, Almirall, Amgen, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer, and UCB, Neal Bhatia Consultant of: AbbVie, Almirall, Arcutis, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, InCyte, ISDIN, Johnson & Johnson, Leo Pharma, Lilly, Ortho, Pfizer, Regeneron, Sanofi, Stemline, and Sun Pharma, Grant/research support from: Arcutis, Biofrontera, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Galderma, Leo Pharma, Lilly, and Ortho, Lynda Spelman Consultant of: AbbVie, Amgen, Anacor, Ascend, Astellas, AstraZeneca, Blaze Bioscience, Bristol Myers Squibb, Boehringer Ingelheim, Botanix, Celgene, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Hexima, Janssen, Leo Pharma, Mayne, Medimmune, Merck, Merck-Serono, Novartis, Otsuka, Pfizer, Phosphagenics, Photon MD, Regeneron, Roche, Samumed, Sanofi Genzyme, SHR, Sun Pharma ANZ, Trius, UCB, and Zai Lab, Kevin Winthrop Consultant of: AbbVie, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Novartis, Pfizer, Regeneron, Roche, Sanofi, and Union Chimique Belge (UCB), Grant/research support from: Bristol Myers Squibb and Pfizer, Lauren Hippeli Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Renata M Kisa Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Subhashis Banerjee Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Diamant Thaçi Speakers bureau: AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron, Roche, Sandoz-Hexal, Sanofi, Target-Solution, and UCB, Consultant of: AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron, Roche, Sandoz-Hexal, Sanofi, Target-Solution, and UCB, Grant/research support from: AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron, Roche, Sandoz-Hexal, Sanofi, Target-Solution, and UCB.

Background:Comorbidities and extra-articular manifestations (EAMs) substantially increase disease burden and mortality risk in patients (pts) with ankylosing spondylitis (AS).1,2Tumour necrosis factor inhibitors (TNFi) are highly efficacious and effective in AS treatment (tx), and are used after inadequate response to non-steroidal anti-inflammatory drugs.3,4However, the impact of TNFi on the incidence of comorbidities and EAMs in pts with AS is unknown.5Objectives:To determine the incidence of comorbidities and EAMs in TNFi vs non-TNFi treated pts with AS in the US.Methods:This was a retrospective, observational cohort study using data from 3 healthcare insurance claims databases: Multi-Payer Claims Database (MPCD Optum Insight; 2007–2010), Truven MarketScan®(2010–2014) and US Medicare Fee-for-Service Claims database (2006–2014). Eligible pts: ≥20 years (yrs) for MarketScan/MPCD or ≥65 yrs for Medicare, had an AS diagnosis (≥2 International Classification of Disease, 9thversion [ICD-9] diagnosis codes of 720.0 from a rheumatologist) and ≥12 months’ continuous medical and pharmacy enrolment prior to AS diagnosis (AS index date). Pts with AS not receiving tx were excluded. Tx exposure was reported from the first date of a new prescription/administration of an AS tx (no prior exposure) after the AS index date. Crude incidence rates (IR; shown as cases/100 pt-yrs) were calculated for EAMs (uveitis, psoriasis [PSO], psoriatic arthritis [PsA], inflammatory bowel disease [IBD]), with follow-up until the earliest of: death, lost medical/pharmacy coverage, study period end, first outcome occurrence, tx switch/discontinuation. Hazard ratios (HRs) of comorbidities (hospitalised infection, solid cancers) and EAMs for propensity score (PS)-matched pt groups were calculated using Cox proportional hazard regression models. Pts with the specific comorbidity/EAM of interest prior to AS index date were excluded. PS analyses assessed probability of TNFi initiation vs non-TNFi tx and adjusted for factors including comorbidities and demographics. HRs with confidence intervals crossing 1 are not reported.Results:20,460 pts with AS were eligible (MPCD: 2,384; MarketScan: 9,032; Medicare: 9,044). In all databases, crude IR of EAMs were higher for TNFi vs non-TNFi treated pts (Figure 1). In the PS-matched cohort, incidences of hospitalised infections were lower in TNFi vs non-TNFi treated pts from the MarketScan and Medicare databases (Figure 2). Higher incidences of solid cancers and EAMs were observed in TNFi vs non-TNFi treated pts; Medicare data (Figure 2). A higher risk of PsA and PSO was seen in TNFi vs non-TNFi treated pts; MarketScan data (Figure 2). PS-matched cohort data from the MPCD database were non-significant.Conclusion:Despite strong efficacy in treating AS-related signs and symptoms, similar incidence of comorbidities and increased incidence of some EAMs (IBD, PSO/PsA, uveitis) was seen in TNFi vs non-TNFi treated pts in the PS-matched analyses. This may be due to channelling of pts with more severe AS to receive TNFi, despite the PS-matched analysis aiming to overcome this. Moreover, prior medical history of Medicare pts may not be captured in the database, as pts are typically older with longer disease durations. While these results confirm previous findings,6a prospective observational study is required to generalise to pts outside the US.References:[1]Stolwijk C. Ann Rheum Dis 2015;74:1373–8;[2]Bremander A. Arthritis Care Res 2011;63:550–6;[3]Braun J. Scand J Rheumatol 2005;34:178–90;[4]Ji X. Front Pharmacol 2019;10:1476;[5]Maxwell LJ. Cochrane Database Syst Rev 2015:CD005468;[6]Walsh J. J Pharm Health Serv Res 2018;9:115–21.Acknowledgments:This study was funded by UCB Pharma. Editorial services were provided by Costello Medical.Disclosure of Interests: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, Kevin Winthrop Grant/research support from: Bristol-Myers Squibb, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Pfizer Inc, Roche, UCB, Rhonda Bohn Consultant of: UCB Pharma, Benjamin Chan: None declared, Robert Suruki Employee of: UCB Pharma, Jeffrey Stark Employee of: UCB Pharma, Huifeng Yun Grant/research support from: Bristol-Myers Squibb and Pfizer, Sarah Siegel: None declared, Lang Chen: None declared, Jeffrey Curtis Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corona, Crescendo, Genentech, Janssen, Pfizer, Roche and UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corona, Crescendo, Genentech, Janssen, Pfizer, Roche and UCB Pharma

Background:Upadacitinib (UPA) is an oral JAK inhibitor approved for the treatment of rheumatoid arthritis (RA). The background rate of herpes zoster (HZ) in patients (pts) with RA is around 0.98/100 person years (PY)1. Pts with RA receiving JAK inhibitors have been reported to have an increased risk of HZ.Objectives:To evaluate the incidence and risk factors for HZ in pts with RA receiving UPA relative to active comparators in the Phase 3 clinical trial program.Methods:The incidence rate of HZ was determined in pts receiving UPA (as monotherapy [mono] or combination therapy) in five randomized Phase 3 trials (SELECT-EARLY, SELECT-MONOTHERAPY, SELECT-NEXT, SELECT-COMPARE, and SELECT-BEYOND), of which 4 evaluated both the UPA 15 and 30 mg once-daily (QD) doses and 1 trial (SELECT-COMPARE) evaluated only the 15 mg QD dose. Incidence of HZ was also determined in pts receiving adalimumab (ADA) + methotrexate (MTX) in SELECT-COMPARE and MTX mono in SELECT-EARLY. Risk factors for HZ were assessed using univariate and multivariate Cox regression models. Data cut-off was 30 June 2019.Results:Overall, 2629 pts who received UPA 15 mg QD (4565.8 patient-years [PY]), 1204 pts who received UPA 30 mg QD (2309.7 PY), 579 pts who received ADA + MTX (768.6 PY), and 314 pts who received MTX mono (456.0 PY) were analyzed. Fewer than 5% of pts across the treatment groups reported prior HZ vaccination. HZ (n/100 PY [95% CI]) occurred in 142 pts (3.1 [2.6–3.7]) with UPA 15 mg, 126 pts (5.5 [4.5–6.5]) with UPA 30 mg, 8 pts (1.0 [0.4–2.1]) with ADA + MTX, and 5 pts (1.1 [0.4–2.6]) with MTX mono. Most of the HZ cases (~71%) with UPA (Table) and all cases with ADA + MTX and MTX mono involved a single dermatome. Ophthalmic involvement was seen in 6 (4.2%) and 3 (2.4%) cases in the UPA 15 and 30 mg groups, respectively, and unilateral involvement with multiple dermatomes was seen in 26 (18.3%) and 23 (18.3%) cases. There was a single case of HZ meningitis reported in a Japanese pt on UPA 30 mg. In multivariate analyses, prior history of HZ and Asian region were associated with an increased risk of HZ in both the UPA groups (p≤0.01;Figure). In addition, pts ≥65 years old had increased risk of HZ in the 15 mg group.Conclusion:HZ events in pts with RA receiving UPA were more common in the 30 mg vs 15 mg group, and in both UPA groups compared with the ADA + MTX and MTX groups.References:[1]Smitten AL, et al. Arthritis Rheum 2007;57:1431–8Table.Summary of extent of involvement in pts with HZCategories, n (%)aAny UPA 15 mg QD(N=2629)Any UPA 30 mg QD(N=1204)Total patients with ≥1 HZ event142 (5.4)126 (10.5)Single dermatome101 (71.1)89 (70.6)Ophthalmic involvement6 (4.2)3 (2.4)HZ Oticus (Ramsay Hunt Syndrome)2 (1.4)1 (0.8)Multidermatomal (unilateral)b26 (18.3)23 (18.3)Disseminated, cutaneous only (no CNS involvement)c7 (4.9)8 (6.3)Disseminated with CNS or visceral involvement01 (0.8)dMissing8 (5.6)5 (4.0)aPts may fall into >1 category;b≤2 adjacent dermatomes;c≥3 dermatomes, unilateral nonadjacent dermatomes, or bilateral dermatomes;dHZ meningitisFigure.Multivariable-adjusted risk factors for HZ in pts receiving UPADisclosure of Interests: :Kevin Winthrop Grant/research support from: Bristol-Myers Squibb, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Pfizer Inc, Roche, UCB, Peter Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Kunihiro Yamaoka Speakers bureau: AbbVie GK, Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd, Mitsubishi-Tanabe Pharma Corporation, Pfizer Japan Inc., and Takeda Pharmaceutical Company Ltd, Eduardo Mysler Grant/research support from: AbbVie, Lilly, Pfizer, Roche, BMS, Sandoz, Amgen, and Janssen., Consultant of: AbbVie, Lilly, Pfizer, Roche, BMS, Sandoz, Amgen, and Janssen., Leonard Calabrese Consultant of: AbbVie, GSK, Bristol-Myers Squibb, Genentech, Janssen, Novartis, Sanofi, Horizon, Crescendo, and Gilead, Speakers bureau: Sanofi, Horizon, Crescendo, Novartis, Genentech, Janssen, and AbbVie, Nasser Khan Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jose Jeffrey Enejosa Shareholder of: AbbVie, Employee of: AbbVie, Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jessica Suboticki Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jeffrey R. Curtis Grant/research support from: Abbvie, Amgen, BMS, Corrona, Crescendo, Janssen, Pfizer, Regeneron/Sanofi, and UCB, Consultant of: AbbVie, Amgen, BMS, Corrona, Crescendo, Janssen, Pfizer, Sanofi/Regeneron, and UCB

BackgroundUpadacitinib (UPA) 15 mg once daily (QD) has demonstrated efficacy and safety in patients with psoriatic arthritis (PsA) for up to 56 weeks in the Phase 3 SELECT-PsA 1 and 2 trials.1,2ObjectivesThis post hoc analysis of these studies explored the association of baseline characteristics and short-term responses with achievement of minimal disease activity (MDA) and Disease Activity Index for Psoriatic Arthritis (DAPSA) low disease activity (LDA).MethodsData were pooled from patients with prior inadequate response or intolerance to ≥1 non-biologic (b) DMARDs (SELECT-PsA 1) or ≥1 bDMARDs (SELECT-PsA 2) originally randomized to UPA 15 mg QD. Logistic regression models were used to assess the association between baseline characteristics and short-term (Week 12) responses with achieving MDA or DAPSA LDA at 56 weeks, sustained MDA (MDA at Weeks 36 and 56), or sustained DAPSA LDA (DAPSA LDA at Weeks 36, 44, and 56). Each predictor was evaluated separately in an initial model that included effects for study and concurrent non-bDMARD use. Odds ratios and concordance (c-)statistics were used to determine the predictive accuracy. Statistically significant predictors were then evaluated simultaneously using stepwise logistic regression with the Akaike Information Criterion for model-building.ResultsOf 640 patients included in the analysis, 40% and 47% achieved MDA and DAPSA LDA, respectively, at 56 weeks. Evaluated separately, younger age, sex (male), geographic region, lower weight, lower body mass index, the presence of dactylitis or enthesitis, and lower scores of Patient’s Assessment of Pain (Pt-Pain), Patient’s Global Assessment (PtGA), tender joint count in 68 joints, and Health Assessment Questionnaire-Disability Index (HAQ-DI) were significant baseline predictors for achieving MDA and DAPSA LDA at Week 56. Lower Pt-Pain (Weeks 12–24) and PtGA (Weeks 16–24) scores were strongly predictive (c-statistics >0.8) of achieving MDA at Week 56, and both measures (from Week 8) were moderately predictive (c-statistics >0.7) of achieving DAPSA LDA. Evaluated simultaneously with several baseline characteristics, lower Pt-Pain and HAQ-DI scores at Week 12 were included in models strongly predictive of achieving MDA (c-statistic=0.850; Figure 1) and DAPSA LDA (c-statistic=0.840; Figure 2) at Week 56. For each 1-point increase in Pt-Pain or HAQ-DI scores at Week 12 (after adjusting for other effects in the model), patients were less likely to achieve MDA (by 32% or 56%, respectively) or DAPSA LDA (by 23% or 31%, respectively) at Week 56. Predictors for achieving sustained MDA and sustained DAPSA LDA were generally similar to those identified for achieving MDA and DAPSA LDA, respectively.ConclusionIn patients with PsA receiving UPA 15 mg, baseline characteristics and early responses strongly predicted achievement of MDA or DAPSA LDA at Week 56. This may guide considerations of treatment targets in clinical trials and encourage physicians to further optimize treatment of their patients in clinical practice.References[1]McInnes IB, et al. Ann Rheum Dis 2020;79:16–7.[2]Mease PJ, et al. Rheumatol Ther 2021 [Epub ahead of print].AcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, review, and approval of the abstract. No honoraria or payments were made for authorship. Medical writing support was provided by Hilary Wong, PhD, of 2 the Nth (Cheshire, UK), which was funded by AbbVie.Disclosure of InterestsDaniel Aletaha Consultant of: AbbVie, Grünenthal, Janssen, Medac, Merck, Mitsubishi/Tanabe, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Grünenthal, Janssen, Medac, Merck, Mitsubishi/Tanabe, Pfizer, Roche, and UCB, Philip J Mease Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, and Janssen, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, and Janssen, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, and Janssen, Ralph Lippe Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Frank Behrens Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Chugai, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Chugai, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: Chugai, GlaxoSmithKline, Janssen, Pfizer, and Roche, Derek Haaland Speakers bureau: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, Takeda, and UCB, Consultant of: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, Takeda, and UCB, Grant/research support from: AbbVie, Adiga Life Sciences, Amgen, Bristol-Myers Squibb, Can-Fite BioPharma, Celgene, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Regeneron, Sanofi, and UCB, Penelope Palominos Speakers bureau: AbbVie, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Janssen, Novartis, Pfizer, and UCB, Apinya Lertratanakul Shareholder of: formerly of AbbVie, Employee of: former employee of AbbVie, Michael Lane Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Kevin Douglas Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Peter Nash Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB, Arthur Kavanaugh Speakers bureau: AbbVie, Amgen, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Janssen, Novartis, Pfizer, and UCB

BackgroundPatients with PsA and axial involvement have higher disease activity and greater reductions in quality of life;1 however, there are no accepted criteria for identifying axial involvement in PsA.ObjectivesThe objective of this post-hoc analysis is to assess the efficacy of upadacitinib (UPA), a Janus kinase inhibitor, on axial symptoms in patients with active PsA and axial involvement defined by investigator assessment and PRO-based criteria from two phase 3 SELECT trials.2,3MethodsPatients with active PsA (≥3 swollen joints and ≥3 tender joints) and prior inadequate response or intolerance to ≥1 non-biologic (SELECT-PsA 1) or ≥1 biologic (SELECT-PsA 2) DMARD were randomly assigned to once daily oral UPA 15 mg or 30 mg, placebo (PBO), or every other week subcutaneous adalimumab (ADA) 40 mg (SELECT-PsA 1 only).2,3 At baseline, axial involvement in PsA was determined by investigator assessment based on the totality of clinical information, such as duration and character of back pain, age of onset, and previous imaging. In addition to investigator assessment, PRO-based criteria for axial involvement (BASDAI ≥4 and BASDAI Question 2 ≥4 at baseline) were applied for this analysis to identify patients with active disease. Efficacy in the sub-group of patients defined using both investigator assessment and PRO-based criteria was evaluated at week 24 for UPA 15 mg vs PBO and ADA (SELECT-PsA 1 only). Data were analyzed using mixed-effect model repeated measures (MMRM) or non-responder imputation (NRI), with nominal P-values shown.ResultsBased on investigator assessment alone, 31.3% (n=534/1704) of patients in SELECT-PsA 1 and 34.2% (n=219/641) in SELECT-PsA 2 were defined as having axial involvement. When both investigator assessment and PRO-based criteria were applied, 23.1% (n=393/1704) of patients in SELECT-PsA 1, or 73.6% (n=393/534) of those defined using investigator assessment alone, and 27.5% (n=176/641) in SELECT-PsA 2, or 80.4% (n=176/219) using investigator assessment alone, met the combined criteria for axial involvement. In both studies, UPA 15 mg showed significantly greater clinical responses vs PBO at week 24 across all endpoints assessed (Figure 1). In SELECT-PsA 1, UPA showed numerically greater responses than ADA at week 24 across all BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS) endpoints. The proportion of patients achieving ASDAS clinically important improvement (CII) at week 24 was significantly greater with UPA vs ADA based on nominal P-value.ConclusionPatients with active PsA and axial involvement defined by both investigator assessment and PRO-based criteria demonstrated statistically greater clinical responses related to their axial involvement with UPA 15 mg compared to PBO, and consistently numerically higher responses compared to ADA, at week 24 in the SELECT-PsA trials. Findings from this post-hoc analysis are consistent with previous data based on investigator assessment alone.4References[1]Mease PJ et al. J Rheumatol. 2018; 45(10):1389-96[2]McInnes IB et al. N Engl J Med. 2021; 384(13):1227-39[3]Mease PJ et al. Ann Rheum Dis. 2020; 80(3):312-20[4]Deodhar A et al. Arthritis Rheumatol. 2020; 72(Suppl 10)AcknowledgementsAbbVie funded these studies and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. No honoraria or payments were made for authorship. Medical writing support was provided by Monica R.P. Elmore, PhD of AbbVie.Disclosure of InterestsXenofon Baraliakos Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, and UCB, R Ranza Speakers bureau: AbbVie, Janssen, Novartis, and Pfizer, Consultant of: AbbVie, Janssen, Novartis, and Pfizer, Andrew Ostor Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Gilead, MSD, Novartis, Pfizer, and Roche, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Gilead, MSD, Novartis, Pfizer, and Roche, francesco ciccia Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, MSD, Novartis, Pfizer, Janssen, Sanofi, Sandoz, Galapagos, Sobi, and UCB, Grant/research support from: AbbVie, Celgene, Pfizer, Roche, and UCB, Laura Coates Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, MSD, Novartis, Pfizer, Janssen, Sanofi, Sandoz, Galapagos, Sobi, and UCB, Grant/research support from: AbbVie, Celgene, Pfizer, Roche, and UCB, Simona Rednic Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, and Pfizer, Grant/research support from: AbbVie, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Pfizer, and UCB, Jessica A. Walsh Consultant of: AbbVie, Amgen, Eli Lilly, Merck, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Eli Lilly, Merck, Novartis, Pfizer, and UCB, Tianming Gao Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Apinya Lertratanakul Shareholder of: Formerly of AbbVie, Employee of: Former employee of AbbVie, In-Ho Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Fabiana Ganz Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Kevin Douglas Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Atul Deodhar Consultant of: AbbVie, Amgen, Aurinia, BMS, Boehringer Ingelheim, GSK, Janssen, Lilly, MoonLake, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, GSK, Lilly, Novartis, Pfizer and UCB

Dasheng Leow of the National Tsing Hua University used (Eur. J. Org. Chem. 2014, 7347) photolysis to activate the air oxidation of hydrazine to generate diimide, that then reduced 1 selectively to 2. Kevin M. Peese of Bristol-Myers Squibb effected (Org. Lett. 2014, 16, 4444) ring-closing metathesis of 3 followed by in situ reduction to form 4. Jitendra K. Bera of the Indian Institute of Technology Kanpur effected (J. Am. Chem. Soc. 2014, 136, 13987) gentle oxidative cleavage of cyclooctene 5 to the dialde­hyde 6. Arumugam Sudalai of the National Chemical Laboratory observed (Org. Lett. 2014, 16, 5674) high regioselectivity in the oxidation of the alkene 7 to the ketone 8. Hao Xu of Georgia State University also observed (J. Am. Chem. Soc. 2014, 136, 13186) high regioselectivity in the oxidation of the alkene 9 with 10, leading to the urethane 11. Justin Du Bois of Stanford University developed (J. Am. Chem. Soc. 2014, 136, 13506) mild conditions for the net double amination of the alkene 12 with 13, leading to 14. Jiaxi Xu and Pingfan Li of the Beijing University of Chemical Technology devised (Org. Lett. 2014, 16, 6036) a protocol for the allylic thiomethylation of an alkene with 16, converting 15 to 17. Matthias Beller of the Leibniz-Institüt für Katalyse combined (Chem. Eur. J. 2014, 20, 15692) hydroformylation, aldol condensation, and reduction to convert the alkene 18 to the ketone 19. Phil S. Baran of Scripps/La Jolla added (Angew. Chem. Int. Ed. 2014, 53, 14382) the diazo dienone 21 to the alkene 20 to give, after exposure to HCl, the arylated product 22. Markus R. Heinrich of the Friedrich-Alexander-Universität Erlangen-Nürnberg employed (Chem. Eur. J. 2014, 20, 15344) Selectfluor as both an oxidizing and a fluorinating agent in the related addition of 24 to 23 to give 25. Debabrata Maiti at the Indian Institute of Technology Bombay activated (J. Am. Chem. Soc. 2014, 136, 13602) the ortho position of 27, then added that interme­diate to 26 to give 28.

Chaozhong Li of the Shanghai Institute of Organic Chemistry reported (J. Am. Chem. Soc. 2012, 134, 10401) the silver nitrate catalyzed decarboxylative fluorination of carboxylic acids, which shows interesting chemoselectivity in substrates such as 1. A related decarboxylative chlorination was also reported by Li (J. Am. Chem. Soc. 2012, 134, 4258). Masahito Ochiai at the University of Tokushima has developed (Chem. Commun. 2012, 48, 982) an iodobenzene-catalyzed Hofmann rearrangement (e.g., 3 to 4) that proceeds via hypervalent iodine intermediates. The dehydrating agent T3P (propylphosphonic anhydride), an increasingly popular reagent for acylation chemistry, has been used (Tetrahedron Lett. 2012, 53, 1406) by Vommina Sureshbabu at Bangalore University to convert amino or peptide acids such as 5 to the corresponding thioacids with sodium sulfide. Jianqing Li and co-workers at Bristol-Myers Squibb have shown (Org. Lett. 2012, 14, 214) that trimethylaluminum, which has long been known to effect the direct amidation of esters, can also achieve the direct coupling of acids and amines, such as in the preparation of amide 8. The propensity of severely hindered 2,2,6,6-tetramethylpiperidine (TMP) amides such as 9 to undergo solvolysis at room temperature has been shown (Angew. Chem. Int. Ed. 2012, 51, 548) by Guy Lloyd-Jones and Kevin Booker-Milburn at the University of Bristol. The reaction proceeds by way of the ketene and is enabled by sterically induced destabilization of the usual conformation that allows conjugation of the nitrogen lone pair with the carbonyl. Matthias Beller at Universität Rostock has found (Angew. Chem. Int. Ed. 2012, 51, 3905) that primary amides may be transamidated via copper(II) catalysis. The conditions are mild enough that an epimerization-prone amide such as 11 undergoes no observable racemization during conversion to amide 13. A photochemical transamidation has been achieved (Chem. Sci. 2012, 3, 405) by Christian Bochet at the University of Fribourg that utilizes 385-nm light to activate a dinitroindoline amide in the presence of amines such as 15, which produces the amide 16. Notably, photochemical cleavage of the Ddz protecting group occurs at a shorter wavelength of 300 nm.