Efficacy and safety of upadacitinib over 84\u2009weeks in Japanese patients with rheumatoid arthritis (SELECT-SUNRISE)

Abstract

Background The objective of the study was to evaluate the efficacy and safety of upadacitinib over 84\u2009weeks in Japanese patients with active rheumatoid arthritis (RA) and an inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs. Methods All patients completing a 12-week, randomized, double-blind treatment period entered a blinded extension and continued upadacitinib 7.5, 15, or 30\u2009mg once daily (QD), or were switched from placebo to upadacitinib 7.5, 15, or 30\u2009mg QD. Efficacy and safety were assessed over 84\u2009weeks. Results Of 197 randomized patients, 187 (94.9%) completed the 12-week period and entered the blinded extension; 152 (77.2%) patients were ongoing at week 84. At week 84, the proportions of patients achieving a 20% improvement in American College of Rheumatology criteria (ACR20) were 85.7%, 77.6%, and 58.0% with continued upadacitinib 7.5, 15, and 30\u2009mg, respectively (nonresponder imputation), and were similar in patients who had switched from placebo. Favorable response rates were also observed for more stringent measures of response (ACR50/70) and remission (defined by the Disease Activity Score of 28 joints with C-reactive protein, Clinical Disease Activity Index, or Simplified Disease Activity Index). The 15\u2009mg and 30\u2009mg doses of upadacitinib were associated with more rapid and numerically higher initial responses for some measures of disease activity and remission compared with the 7.5\u2009mg dose. Rates of adverse events, infection, opportunistic infection, serious infection, and herpes zoster were lower with upadacitinib 7.5 and 15\u2009mg versus 30\u2009mg. Conclusions Upadacitinib demonstrated sustained efficacy and was well tolerated over 84\u2009weeks in Japanese patients with RA, with upadacitinib 15\u2009mg offering the most favorable benefit–risk profile. Trial registration ClinicalTrials.gov NCT02720523 . Registered on March 22, 2016.