ACHIEVEMENT AND MAINTENANCE OF REMISSION WITH UPADACITINIB IN PATIENTS WITH MODERATE-TO-SEVERE RHEUMATOID ARTHRITIS IN A REAL-WORLD SETTING: 1-YEAR OUTCOMES FROM THE UPHOLD STUDY

Background: Upadacitinib (UPA), an oral reversible JAK inhibitor, has shown efficacy with an acceptable safety profile in patients (pts) with moderate-to-severe RA in the SELECT clinical trials. However, data on the effectiveness and safety of UPA in a real-world (RW) setting, which may differ from clinical trials, are limited. Objectives: To assess the co-primary endpoints of achievement of remission (REM) at 6 months (mo) and maintenance of REM after 12 mo of UPA treatment in pts with moderate-to-severe RA in RW practice. Methods: UPHOLD (NCT04497597) is an ongoing, international, observational cohort study of UPA-naïve pts aged ≥18 years with moderate-to-severe RA who received UPA 15 mg, with the decision to initiate UPA made before enrollment. This 12-mo interim analysis reports data between the start date of 16 Oct 2020 and data cutoff of 10 Aug 2023 (including all pts within the 12-mo visit window). The co-primary endpoints were: i) % of pts receiving UPA who achieved DAS28(CRP) REM (<2.6) at 6 mo and, of these, ii) % of pts who maintained REM (or had a ≤0.6-point increase in DAS28[CRP]) at 12 mo (analysed by modified non-responder imputation [mNRI; discontinuations before prespecified timepoints were treated as non-responders] and as observed [AO] in modified full analysis set [mFAS]1 and mFAS2, respectively). mFAS1 included all pts within the FAS (all pts receiving ≥1 UPA dose) who completed 6 mo of treatment and had DAS28(CRP) data available, and pts who discontinued before 6 mo; mFAS2 included all pts achieving REM within mFAS1 who completed 12 mo of treatment and had DAS28(CRP) data available, and pts who discontinued between 6 and 12 mo. Additional efficacy endpoints included: % of pts achieving DAS28(CRP) low disease activity (LDA; ≤3.2) at 6 mo who maintained LDA at 12 mo (analysed by mNRI in mFAS1/mFAS2 and AO); and % of pts achieving CDAI/SDAI REM (≤2.8/<3.3) at 12 mo (analysed AO). All treatment-emergent adverse events (TEAEs) in the FAS occurring by the cutoff date are reported as exposure-adjusted event rates (EAERs; events per 100 pt-years [E/100PY]). Results: Of 1719 participants, 1717 were enrolled and 1701 comprised the FAS. Baseline (BL) pt characteristics have been reported previously. Of FAS pts, 48.4% initiated UPA as monotherapy and 51.6% in combination with conventional synthetic DMARDs. Of 1523 pts receiving prior therapy, 64.3% received ≥1 biologic DMARD and 18.1% ≥1 targeted synthetic DMARD. A total of 400/1719 (23.3%) pts prematurely discontinued the study before 12 mo; the most common primary reasons were lack of efficacy (9.9%) and TEAEs (6.6%). Of 1074 pts in mFAS1, 46.5% (mNRI) and 55.3% (AO) were in DAS28(CRP) REM at 6 mo. Of 340 pts in mFAS2, 79.1% (mNRI) and 84.9% (AO) maintained REM at 12 mo (Figure 1A). The % of pts achieving DAS28(CRP) LDA at 6 mo who maintained LDA at 12 mo followed a similar trend (Figure 1B). The % of pts achieving DAS28(CRP), CDAI (≤2.8), and SDAI (≤3.3) REM at 12 mo were 59.8%, 28.0%, and 28.3%, respectively (FAS; AO). Of pts initiating UPA at BL as mono- or combination therapy who achieved DAS28(CRP) REM at 6 mo, had DAS28(CRP) data available at 6 and 12 mo, and continued UPA at 12 mo (or discontinued between 6 and 12 mo) and maintained their initial therapy scheme, 80.5% (136/169) and 79.4% (104/131), respectively, maintained REM at 12 mo (mNRI). There were 2436 TEAEs (101.45 E/100 PY), with EAERs for herpes zoster, serious infection, and hepatic disorder of 3.12, 2.62, and 2.46 E/100 PY, respectively (Table 1). EAERs for MACE, malignancy, and thrombotic events were low and consistent with those reported in long-term UPA clinical trials. Conclusion: UPA 15 mg is effective for the treatment of moderate-to-severe RA in RW practice, with >79% of pts who achieved DAS28(CRP) REM by 6 mo maintaining REM through 12 mo. The benefit-risk profile of UPA remains favorable in RW practice and is consistent with phase 3 clinical trial data. REFERENCES: [1] Conaghan PG et al. Drug Saf 2021;44:515–30. [2] Östör A et al. ACR 2023:POS 0424. [3] Burmester GR et al. RMD Open 2023;e002735. Acknowledgements: AbbVie and the authors thank the participants, study sites, and study investigators who are participating in this study. The authors would also like to thank Ivan Lagunes-Galindo from AbbVie and Gabriele Accetta from ICON for their invaluable support. AbbVie funded this study and contributed to its design, research, analysis, data collection, interpretation of data, and the review and approval of this abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship. Medical writing support was provided by Katerina Betsista, MD, of 2 the Nth (Cheshire, UK) and was funded by AbbVie. Disclosure of Interests: Andrew Östör AbbVie, GSK, Janssen, Lilly, Novartis, and Pfizer, Eugen Feist AbbVie, BMS, Galapagos, Lilly, MSD, Novartis, Pfizer, Roche, and Sobi, Prodromos Sidiropoulos AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and UCB, Jérôme Avouac Honoraria: AbbVie, AstraZeneca, Biogen, BMS, Fresenius Kabi, Galapagos, Janssen, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Roche-Chugai, Sandoz, and Sanofi; research grants: BMS, Fresenius Kabi, Galapagos, Novartis (Dreamer), and Pfizer (Passerelle), Martin Rebella Honoraria and/or support to participate in academic events: AbbVie, Bayer, Pfizer, and Roche, Rajaie Namas: None declared, Erin McDearmon-Blondell AbbVie, AbbVie, Tianming Gao AbbVie, AbbVie, Nasser Khan AbbVie, AbbVie, Sander Strengholt AbbVie, AbbVie, Suzan Attar Speaker fees: AbbVie, Amgen, AstraZeneca, BMS, Gilead, GSK, Hikma, Janssen, Lilly, Novartis, Organon, Pfizer, Roche, Sandoz, Sanofi, and Takeda, Research grants and advisory honoraria: AbbVie, Amgen, AstraZeneca, BMS, Gilead, GSK, Hikma, Janssen, Lilly, Novartis, Organon, Pfizer, Roche, Sandoz, Sanofi, and Takeda. DOI: 10.1136/annrheumdis-2024-eular.2238 Keywords: Real-world evidence, Disease-modifying Drugs (DMARDs), Targeted synthetic drugs, Safety Citation: , volume 83, supplement 1, year 2024, page 794Session: Rheumatoid arthritis (Poster View)

Real-world evidence, Disease-modifying Drugs (DMARDs), Targeted synthetic drugs, Safety