gms | German Medical Science

Introduction: Upadacitinib (UPA), an oral, reversible JAK inhibitor, has shown efficacy and an acceptable safety profile in rheumatoid arthritis (RA) [1], [2], [3], [4], [5], [6]. However, real-world data on UPA in clinical practice is limited [7], [8]. This sub-analysis of the UPHOLD study presents 12-month data in patients with moderate/severe RA from Germany, Austria, and Switzerland.

Methods: UPHOLD (NCT04497597) is a prospective, open-label, multi-country, observational study of real-world UPA-naïve adults (aged ≥18 years) with moderate/severe RA, who received UPA 15 mg once daily. Co-primary endpoints were proportion of patients achieving DAS28-CRP remission (<2.6) at Month 6 (M6) and maintenance of remission at M12 (DAS28-CRP<2.6 or ≤0.6-point increase in DAS28-CRP in patients in remission at M6). Additional efficacy endpoints included proportion of patients achieving DAS28-CRP low disease activity (LDA; ≤3.2) at M6, maintenance of LDA at M12 (DAS28-CRP≤3.2 or ≤0.6-point increase in DAS28-CRP in patients in LDA at M6), and change from baseline in patient-reported outcomes (PROs) through M12. DAS28-CRP remission/LDA were analyzed as observed (AO) in a modified full analysis set (mFAS; FAS patients received ≥1 UPA dose): mFAS1 (patients with data available at M6 or discontinuation before M6); mFAS2 (patients achieving remission/LDA in the mFAS1 with data available at M12 or discontinuation between M6 and M12). Safety (reported as exposure-adjusted event rates) and PRO endpoints were assessed in the FAS.

Results: Of 268 patients, 262 received ≥1 UPA dose (FAS). A total of 70/268 (26.1%) patients discontinued by M12. At UPA initiation, mean age was 57.8 years and 76.3% were female (Table 1). Of patients with available data, 68.8%/79.6% achieved DAS28-CRP remission/LDA, respectively, at M6 (mFAS1) and 84.0%/92.8% maintained DAS28-CRP remission/LDA at M12 (mFAS2; Figure). Improvements from baseline to M12 were observed across PROs including pain, functional disability, and fatigue. Due to the small sample size and limited exposure safety data should be interpreted with caution, however the overall safety profile was generally consistent with previous reports with no new safety signals observed (Table 2).

Conclusion: This study suggests UPA is effective for the treatment of moderate/severe RA in real-world practice. The benefit–risk profile of UPA remains favorable in this population, consistent with Phase 3 clinical trials [1], [2], [3], [4], [5], [6], [9], [10]).

Disclosures: Eugen Feist has received honoraria and research grants from AbbVie, BMS, Galapagos, Lilly, MSD, Novartis, Pfizer, Roche, and Sobi.

Sara Bär has received honoraria from AbbVie, Biopharma, Chugai Pharma, Galapagos, GSK, Lilly, Novartis, and UCB.

Maren Sieburg has received research support from Charité and has received honoraria from AbbVie, AstraZeneca, Biogen, BMS, Boehringer Ingelheim, Chugai, Galapagos, Hexal, Janssen, Labcorp, Lilly, Medac, Novartis, Pfizer, Sanofi-Aventis, and UCB.

Jacqueline Detert declares no conflict of interest.

Johannes Resch-Passini has received honoraria and research grants from AbbVie, Amgen, BMS, Lilly, Galapagos, Janssen, MSD, Novartis, and UCB.

Heino Prillwitz has received research grants, consultation and/or speaker honoraria from AbbVie, Amgen, Boehringer, Celgene, Grünenthal, Novartis, Pfizer, Roche, Sanofi-Genzyme, and UCB.

Katharina Wiesemann, Sixten Gnüchtel, Pascal Roulin, Monika Praschberger, and Alexandra Rueben are AbbVie employees and may own AbbVie stock or options.

Andrea Rubbert-Roth has received honoraria for lectures and consultation fees from AbbVie, Amgen, BMS, Galapagos, Lilly, MSD, Pfizer, Roche, Sanofi, and UCB.

AbbVie and the authors thank the participants, study sites, and study investigators who are participating in this study. AbbVie funded this study and contributed to its design, research, analysis, data collection, interpretation of data, and the review and approval of this 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. Statistical analyses were provided by ICON plc, which was funded by AbbVie. Medical writing support was provided by Colette Szarka, MPhil, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.