POS1541 LONG-TERM EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS: 3-YEAR RESULTS FROM THE PHASE 3 SELECT-PsA 1 STUDY

Background Upadacitinib (UPA) improved symptoms in patients (pts) with psoriatic arthritis (PsA) with prior inadequate response or intolerance to ≥1 non-biologic disease-modifying antirheumatic drug (nbDMARD-IR) through week (wk) 104 or 2 years of treatment in SELECT-PsA 1 [1] . Objectives To evaluate efficacy and safety of UPA vs adalimumab (ADA) through wk 152 or 3 years from the ongoing long-term open-label extension of SELECT-PsA 1. Methods Pts were randomized to receive UPA 15 mg (UPA15) or UPA 30 mg (UPA30) once daily, ADA 40 mg (ADA) every other wk, or placebo (PBO). At wk 24, PBO pts switched to UPA15 or UPA30. Following approval of UPA15, the protocol was amended so pts on UPA30 switched to UPA15 (earliest at wk 104). Efficacy was assessed through wk 152, and safety through June 13, 2022. Results Of 1704 pts randomized, 911 completed 152 wks of treatment. The proportions of pts achieving. ≥20%/50%/70% improvement in American College of Rheumatology criteria (ACR20/50/70), minimal disease activity (MDA), and ≥75%/90%/100% improvement in Psoriasis Area and Severity Index at wk 152 were generally consistent with those at wk 104 1 . UPA had greater ACR20/50/70 and MDA responses vs ADA, and a greater mean change from baseline (BL) in Health Assessment Questionnaire-Disability Index, pt’s assessment of pain, and Bath Ankylosing Spondylitis Disease Activity Index vs ADA. Change from BL in modified total Sharp/van der Heijde score were similar between UPA30 and ADA, and numerically higher with UPA15 (Table 1 ). The overall UPA safety profile remained unchanged ( Figure 1 ) [1,2] . UPA had numerically higher rates of serious infection (SI), herpes zoster (HZ), anemia, lymphopenia, creatine phosphokinase (CPK) elevation, and non-melanoma skin cancer (NMSC) vs ADA. Increases for SI, HZ, anemia, and CPK elevation with UPA were dose dependent. Rates of major adverse cardiovascular events, venous thromboembolism, and malignancy excluding NMSC were low and generally similar across groups. The most common cause of death was COVID-19. Conclusion Efficacy of UPA in nbDMARD-IR pts with PsA was maintained through 3 years of treatment. No new safety signals were identified. References [1]McInnes IB, et al. Rheumatol Ther 2022;1–18 [Epub ahead of print]. [2]McInnes IB, et al. RMD Open 2021;7(3):e001838. Table 1. Efficacy endpoints at wk 152 UPA15 (n=429) UPA30 a (n=423) ADA (n=429) Proportion of pts (%) NRI AO NRI AO NRI AO ACR20/50/70 64.6/52.0/35.9* 89.8/71.6/ 48.2 63.1/54.1*/ 35.7 87.9/74.4/ 47.8 61.1/46.6/ 28.7 86.2/65.2/ 39.8 Minimal disease activity 37.5 55.1 43.5* 60.3 35.9 50.2 PASI75/90/100 b 50.5/42.5/32.2 69.2/58.5/ 43.4 58.1/46.7/3 7.6 78.6/63.5/ 50.9 54.0/40.8/ 30.3 79.6/59.9/ 44.6 Resolution of enthesitis by Leeds Enthesitis Index c 50.4 75.2 48.9 73.8 46.0 77.0 Resolution of dactylitis by Leeds Dactylitis Index d 65.4 95.2 66.1 97.9 65.4 97.1 Change from BL e MMRM AO MMRM AO MMRM AO Health Assessment Questionnaire- Disability Index -0.51 -0.55 -0.53* -0.58 -0.45 -0.49 Pt’s assessment of pain (numeric rating scale) -3.3* -3.5 -3.3* -3.6 -2.8 -3.0 Bath Ankylosing Spondylitis Disease Activity Index f -3.09 -3.27 -3.16 -3.54 -2.81 -2.71 Modified total Sharp/van der Heijde score 0.21 0.19 0.05 0.04 0.09 0.09 a Following a protocol amendment, all pts on UPA30 switched to UPA15 (earliest switch at wk 104); data are presented by originally randomized group. b Pts with psoriasis affecting ≥3% of body surface area at BL. c Pts with LEI >0 at BL; resolution LEI=0. d Pts with LDI >0 at BL; resolution LDI=0. e Data shown as MMRM (least squares mean) and AO (mean). f Pts with psoriatic spondylitis at BL. n value ranges: UPA15 (99–429), UPA30 (95–423), ADA (89–429). Nominal *p<0.05 UPA vs ADA. ACR20/50/70, ≥20%/50%/70% improvement in American College of Rheumatology criteria; ADA, adalimumab; AO, as observed; BL, baseline; MMRM, mixed effect model repeated measurement; NRI, non-responder imputation; PASI75/90/100, ≥75%/90%/100% improvement in Psoriasis Area and Severity Index; pt, patient; UPA15/30, upadacitinib 15/30 mg once daily; wk, week Acknowledgements AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, and the review and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Carl Davies, MSc, of 2 the Nth (Cheshire, UK), and was funded by AbbVie. Disclosure of Interests Iain McInnes Grant/research support from: AbbVie, AstraZeneca, Bristol Myers Squibb, Celgene, Eli Lilly, Evelo, Causeway Therapeutics, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, and UCB Pharma, Koji Kato Employee of: AbbVie and may hold stock or options, Marina Magrey Consultant of: BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, BMS, and UCB Pharma, Joseph F. Merola Consultant of: AbbVie, Arena, Avotres, Biogen, Bristol Myers Squibb, Celgene, Dermavant, Eli Lilly, EMD Sorono, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB Pharma, Mitsumasa Kishimoto Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Celgene, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB Pharma, Derek Haaland Speakers bureau: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, 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-Genzyme, UCB; and has received honoraria or other fees from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, and UCB Pharma, Yihan Li Employee of: AbbVie and may hold stock or options, Yanxi Liu Employee of: AbbVie and may hold stock or options, Jianzhong Liu Employee of: AbbVie and may hold stock or options, Ralph Lippe Employee of: AbbVie and may hold stock or options, Peter Wung Employee of: AbbVie and may hold stock or options.