1 Fleischmann R, et al. RMD Open 2022;8:e002012. doi:10.1136/rmdopen-2021-002012 ORIGINAL RESEARCH Long-term safety and effcacy of upadacitinib or adalimumab in patients with rheumatoid arthritis: results through 3 years from the SELECT- COMPARE study Roy Fleischmann , 1 Eduardo Mysler, 2 Louis Bessette, 3 Charles G Peterfy, 4 Patrick Durez , 5 Yoshiya Tanaka , 6 Jerzy Swierkot, 7 Nasser Khan, 8 Xianwei Bu, 8 Yihan Li, 8 In-Ho Song 8 To cite: Fleischmann R, Mysler E, Bessette L, et al. Long-term safety and effcacy of upadacitinib or adalimumab in patients with rheumatoid arthritis: results through 3 years from the SELECT- COMPARE study. RMD Open 2022;8:e002012. doi:10.1136/ rmdopen-2021-002012 ► Additional supplemental material is published online only. To view, please visit the journal online (http://dx.doi.org/10. 1136/rmdopen-2021-002012). Received 6 October 2021 Accepted 13 January 2022 For numbered affliations see end of article. Correspondence to Dr Roy Fleischmann; rfeischmann@arthdocs.com Rheumatoid arthritis © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. ABSTRACT Objectives To assess the long-term safety and effcacy of the Janus kinase inhibitor upadacitinib versus adalimumab over 3 years in the ongoing long-term extension (LTE) of SELECT-COMPARE, a randomised controlled phase 3 trial of patients with active rheumatoid arthritis and inadequate response to methotrexate (MTX). Methods Patients on stable background MTX were randomised 2:2:1 to upadacitinib 15 mg, placebo or adalimumab 40 mg. Patients with an insuffcient response were switched by week 26 from placebo to upadacitinib, upadacitinib to adalimumab or adalimumab to upadacitinib. Patients who completed the 48-week double-blind period could enter an LTE for up to 10 years. Safety and effcacy results were analysed here through 3 years. Treatment- emergent adverse events (AEs) were summarised based on exposure to upadacitinib and adalimumab. Effcacy was analysed by original randomised groups (non-responder imputation), as well as separately by treatment sequence (as observed). Results Rates of several AEs were generally comparable between upadacitinib and adalimumab, including AEs leading to discontinuation, serious infections and serious AEs, malignancies, major adverse cardiac events, venous thromboembolism and deaths. Consistent with earlier results, herpes zoster, lymphopaenia, hepatic disorder and CPK elevation were reported at higher rates with upadacitinib versus adalimumab. In terms of effcacy, upadacitinib continued to show numerically better clinical responses than adalimumab over 3 years across all endpoints, including low disease activity and remission. Conclusion The safety profle of UPA 15 mg was consistent with previous study-specifc and integrated safety reports. Higher levels of clinical response continued to be observed with upadacitinib versus adalimumab through 3 years of treatment. INTRODUCTION Rheumatoid arthritis (RA) is a chronic inflammatory joint disease associated with progressive cartilage and bone damage. Affecting approximately 0.5% of the adult population worldwide, 1 RA can lead to functional impairment, loss of mobility and reduced quality of life. To counter these effects and improve long-term prognosis, the Key messages What is already known about this subject? ► Safety and effcacy of upadacitinib have been evaluated in multiple rheumatoid arthritis (RA) populations in six global phase III trials, including SELECT-COMPARE, which demonstrated improve- ments in the signs and symptoms of RA in favour of upadacitinib 15 mg versus adalimumab through 72 weeks. What does this study add? ► Safety and effcacy data through 3 years, including treatment switch data are reported for a Janus ki- nase inhibitor versus a TNF inhibitor. ► The safety profle of upadacitinib 15 mg observed through 3 years was generally similar to adalimum- ab for adverse events of special interest, including malignancies, major adverse cardiac events, venous thromboembolism and deaths. ► Upadacitinib continued to show consistently bet- ter clinical responses compared with adalimumab through 3 years including rates of remission and low disease activity, physical function and pain severity; radiographic progression was inhibited to a similar extent. How might this impact on clinical practice or further developments? ► Based on its favourable beneft–risk profle for the treatment of patients with active RA, upadacitinib 15 mg continues to be a reasonable treatment choice after an inadequate response to methotrexate. on July 30, 2022 by guest. Protected by copyright. http://rmdopen.bmj.com/ RMD Open: first published as 10.1136/rmdopen-2021-002012 on 4 February 2022. Downloaded from