POS0655 LONG-TERM SAFETY AND EFFICACY OF UPADACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS: 3-YEAR RESULTS FROM THE SELECT-EARLY STUDY

Background: Upadacitinib (UPA), an oral Janus kinase inhibitor, demonstrated significant improvements in signs, symptoms, and structural inhibition as monotherapy (mono) vs methotrexate (MTX) MTX-naïve patients (pts) with rheumatoid arthritis (RA) through 48 weeks (wks). 1 Objectives: To report the efficacy safety of UPA MTX mono up to 156 wks pts RA from ongoing long-term extension (LTE) SELECT-EARLY trial. Methods: During 48-wk double-blind study period, were randomized 15 or 30 mg once daily (QD) (titrated 20 mg/wk by Wk 8). At 26, who did not achieve Clinical Disease Activity Index (CDAI) remission (≤2.8) had <20% improvement baseline tender swollen joint count received blinded rescue therapy (addition for groups group). In LTE, open-label treatment last pt reached 48. Efficacy assessments summarized group included American College Rheumatology (ACR) responses, low disease activity (LDA) measures, change modified Total Sharp Score (mTSS; 96 wks). Treatment-emergent adverse events (AEs) per 100 pt-years (PY) on continuous wks. Non-responder imputation was used binary endpoints missing data when prematurely discontinued drug. Results: Of 945 treated, 775 entered LTE drug (including 57 rescued pts; MTX, 33; mg, 17; 7). Overall, 161 (21%) during LTE. 156, higher proportions achieved a 20/50/70% ACR response (ACR20/50/70), LDA, (Figure 1). Change mTSS at favored (data shown). Most AEs numerically more frequent mg. The overall rate serious infection (Table Herpes zoster (HZ), neutropenia, non-melanoma skin cancer (NMSC), creatine phosphokinase (CPK) elevation MTX. Two active tuberculosis (TB) reported each arm; 3 adjudicated gastrointestinal (GI) perforation observed arm. Adjudicated major cardiovascular (MACEs) venous thromboembolic (VTEs) comparable across arms. Conclusion: showed sustained clinically meaningful responses including but rates several AEs, HZ, CPK elevations; no new risks compared previous results. 1,2 References: [1]van Vollenhoven R, et al. Ann Rheum Dis 2019;78:376–7; 2. Cohen SB, 2020;annrheumdis-2020-218510. Table 1. Safety overview E/100 PY (95% CI) (n=314; PY=601.9) QD (n=317; PY=703.4) PY=687.6) Any AE 240.2 (228.0, 252.9) 268.0 (256.0, 280.4) 292.5 (279.8, 305.5) 10.8 (8.3, 13.8) 12.2 (9.8, 15.1) 16.3 (13.4, 19.6) leading discontinuation 6.5 (4.6, 8.9) 7.3 (5.4, 9.5) 7.7 (5.8, 10.1) death 0.7 (0.2, 1.7) 0.9 (0.3, 1.9) 1.0 (0.4, 2.1) Serious 2.5 (1.4, 4.1) 3.3 (2.1, 4.9) 4.4 (2.9, 6.2) Opportunistic excluding TB HZ 0.2 (0.0, 0.9) 0.1 0.8) 0.3 1.1) 0.8 4.5 (3.1, 6.4) 4.7 (3.2, 6.6) Active 0 1.0) NMSC 0.4 (0.1, 1.2) Malignancy other than 2.2) 0.6 1.5) 1.2 (0.5, 2.3) Hepatic disorder 14.1 (11.3, 17.5) 12.5 (10.0, 15.4) 15.0 (12.2, 18.2) GI b 1.3) Neutropenia 2.2 (1.2, 3.7) 5.7 (4.0, 7.8) 1.8 (0.9, 3.3) 10.0) 15.4 (12.6, 18.6) MACE VTE Data censored time addition Includes treatment-emergent (≤30 days after dose drug) non-treatment-emergent deaths. Acknowledgements: AbbVie funded this study; contributed its design; participated collection, analysis, interpretation data; writing, review, approval abstract. No honoraria payments made authorship. Medical writing support provided Russell Craddock, PhD, 2 Nth (Cheshire, UK), AbbVie. Disclosure Interests: Ronald van Speakers bureau: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Galapagos, Gilead, GSK, Janssen, Pfizer, Sanofi, Servier, UCB, Viela Bio, Consultant of: Biogen, Grant/research from: Eli Lilly, Roche, Tsutomu Takeuchi AYUMI, Chugai, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Mitsubishi Tanabe, Novartis, Astellas, Asahi Kasei, Nippon Kayaku, Shionogi, Takeda, Jacob Aelion Amgen, Celgene, Galapagos/Gilead, Genentech, Horizon, Mallinckrodt, Nektar, Nichi-Iko, Regeneron, Selecta, Nilmo Chávez Pablo Mannucci Walter Genentech/Roche, Atul Singhal Aclaris, Idorsia, Oscotec, Roche/Genentech, Jerzy Swierkot Accord, BMS, MSD, Sandoz, Alan Friedman Shareholder May own stock options Employee Nasser Khan stocks Yihan Li Xianwei Bu Justin Klaff Vibeke Strand Arena, Bayer, Boehringer Ingelheim, Celltrion, Ichnos, Inmedix, Kiniksa, Myriad Genetics, Setpoint, UCB