AB0523 LONG-TERM SAFETY AND EFFECTIVENESS OF UPADACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS: RESULTS AT 56 WEEKS FROM THE SELECT-PsA 1 STUDY
Authors: I. McInnes, K. Kato, M. Magrey, J. F. Merola, M. Kishimoto, C. F. Pacheco Tena, D. Haaland, L. Chen, Y. Duan, P. Zueger, J. Liu, R. Lippe, A. Pangan, F. Behrens
Journal: Annals of the Rheumatic Diseases (2021)

Background: In the SELECT-PsA 1 study, through 24 weeks (wks), once daily upadacitinib 15 mg (UPA15) and 30 mg (UPA30) showed improvements in musculoskeletal symptoms, psoriasis, physical function, pain, fatigue, and quality of life, as well as inhibition of radiographic progression in patients (pts) with psoriatic arthritis (PsA) and inadequate response or intolerance to ≥1 non-biologic disease-modifying antirheumatic drug (DMARD). 1 Objectives: To report the efficacy and safety of UPA vs adalimumab (ADA) up to 56 wks from the ongoing long-term extension of SELECT-PsA 1. Methods: Pts received UPA15 or UPA30, ADA 40mg every other wk for 56 wks, or PBO through wk 24 switched thereafter to either UPA15 or UPA30 until wk 56. Efficacy endpoints as listed and defined in the Table 1 were analyzed at wk 56. Results for binary endpoints are based on non-responder imputation analysis; treatments were compared using the Cochran-Mantel-Haenszel test. Results for non-radiographic continuous endpoints are based on mixed model repeated measures model based on as observed data. Radiographic endpoints were analyzed based on linear extrapolation. Treatment-emergent adverse events (TEAEs) per 100 pt years (PY) were summarized for pts who received ≥1 dose of study drug. Table 1. Efficacy Endpoints at Week 56 Endpoint PBO → UPA15 PBO → UPA30 UPA15 UPA30 ADA ACR20, % 73.0 74.1 74.4 74.7 # 68.5 ACR50, % 54.5 60.4 59.7* 60.5 # 51.3 ACR70, % 29.9 35.8 40.6* 43.7 # 31.2 Minimal Disease Activity, % 29.4 35.8 44.8 47.3 # 39.6 PASI75 a , % 58.3 60.2 65.4 63.3 61.1 PASI90 a , % 41.7 53.7 49.1 49.5 46.9 PASI100 a , % 22.3 38.9 34.6 39.5 31.3 Resolution of enthesitis by Leeds Enthesitis Index b , % 38.1 45.5 59.3 58.1 54.0 Resolution of dactylitis by Leeds Dactylitis Index c , % 47.7 59.0 75.0 74.8 74.0 Δ from BL in Bath Ankylosing Spondylitis Disease Activity Index d -3.1 -3.1 -3.3 -3.2 -2.8 Δ from BL in modified total Sharp/van der Heijde Score (mTSS) 0.44 e -0.05 † 0.02 ‡ -0.06 * and †, p≤0.05; for UPA15 vs ADA and PBO, respectively; # and ‡, p≤0.05; for UPA30 vs ADA and PBO, respectively. a for pts with psoriasis affecting ≥3% of body surface area at BL. b for pts with LEI &gt;0 at BL. c for pts with LDI &gt;0 at BL. d for pts with psoriatic spondylitis at BL. e pooled PBO. ACR20/50/70, ≥20%/50%/70% improvement in American College of Rheumatology criteria; ADA, adalimumab; BL, baseline; PASI75/90/100, ≥75%/90%/100% improvement in Psoriasis Area and Severity Index; PBO, placebo; pts, patients; UPA, upadacitinib. Results: Of 1704 pts who received ≥1 dose of study drug, 1419 (83.2%) completed 56 wks of treatment on study drug. Across all treatment groups, the proportions of pts who had achieved ACR20/50/70, MDA, PASI75/90/100, resolution of enthesitis, and resolution of dactylitis were maintained or further improved from wk 24 1 through wk 56; these proportions were generally greater for pts originally randomized to UPA vs ADA (Table 1). At wk 56, mean change from BL in mTSS was similar with UPA15, UPA30, and ADA. Improvements in pts who switched from PBO to UPA were generally similar to those originally randomized to UPA at wk 56. Through wk 56, the rates of TEAEs and serious AEs, including serious infections, were similar in the UPA15 and ADA arms and higher with UPA30 (Figure 1). The rate of herpes zoster was higher with UPA vs ADA in a dose-dependent manner. Malignancies were reported at similar rates among all treatment groups. Adjudicated venous thromboembolic events and major adverse cardiovascular events were reported in all groups with comparable rates. Two deaths were reported with UPA15, 2 with UPA30, and 1 with ADA; 1 death was reported with PBO during the 24-wk PBO-controlled period. Conclusion: Efficacy responses were maintained or further improved with UPA15 and UPA30 over 56 wks and were numerically higher vs ADA. The inhibition of radiographic progression was maintained at wk 56 and was similar with UPA and ADA. At wk 56, improvements in efficacy were observed in pts who switched from PBO to UPA. No new safety findings were observed with longer exposure to UPA. References: [1]McInnes IB et al. Ann Rheum Dis , 2020; 79:12 Figure 1 Acknowledgements: AbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial. AbbVie, Inc was the study sponsor, contributed to study design, data collection, analysis &amp; interpretation, and to writing, reviewing, and approval of final version. No honoraria or payments were made for authorship. Medical writing support was provided by Ramona Vladea, PhD of AbbVie Inc. Disclosure of Interests: Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, UCB Pharma, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, UCB Pharma, Koji Kato Shareholder of: AbbVie, Employee of: AbbVie, Marina Magrey Consultant of: UCB, Novartis, Eli Lilly, Pfizer and Janssen, Grant/research support from: Amgen, AbbVie, and UCB Pharma, Joseph F. Merola Consultant of: Merck, Bristol-Myers Squibb, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and Leo Pharma, Mitsumasa Kishimoto Consultant of: AbbVie, Amgen-Astellas BioPharma, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Celgene, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, Teijin Pharma, and UCB Pharma, Cesar Francisco Pacheco Tena Consultant of: Eli Lilly, AbbVie, Roche, Pfizer, Janssen, Astra-Zeneca, UCB, Gilead, R-Pharm, Sanofi Regeneron, Grant/research support from: Eli Lilly, AbbVie, Roche, Pfizer, Janssen, Astra-Zeneca, UCB, Gilead, R-Pharm, Sanofi Regeneron, Derek Haaland Speakers bureau: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, Consultant of: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, 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-Genzyme, UCB, Liang Chen Shareholder of: AbbVie, Employee of: AbbVie, Yuanyuan Duan Shareholder of: AbbVie, Employee of: AbbVie, Patrick Zueger Shareholder of: AbbVie, Employee of: AbbVie, Jianzhong Liu Shareholder of: AbbVie, Employee of: AbbVie, Ralph Lippe Shareholder of: AbbVie, Employee of: AbbVie, Aileen Pangan Shareholder of: AbbVie, Employee of: AbbVie, Frank Behrens Consultant of: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche, Chugai, BMS, UCB Pharma, Grant/research support from: Pfizer, Janssen, Chugai, Celgene and Roche.