Abstract
OBJECTIVE: To assess the long-term safety and efficacy of upadacitinib over 5 years in Japanese patients with moderate-to-severe active rheumatoid arthritis and an inadequate response to stable doses of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs-IR). METHODS: Japanese patients received upadacitinib 7.5, 15 or 30 mg once per day or placebo for 12 weeks in a double-blind, randomised manner. Patients who completed the placebo-controlled phase entered a long-term extension phase during which they continued the same upadacitinib dose or were switched from placebo to upadacitinib 7.5, 15 or 30 mg once per day. Blinding was maintained until dose switching from upadacitinib 30 mg to 15 mg, prior to the regulatory approval of 15 mg; the earliest switch occurred at week 132. Safety and efficacy were evaluated through week 260. RESULTS: In total, 121/187 (64.7%) patients who entered the long-term extension phase completed the study. The types and frequency of adverse events were comparable with those reported at week 84 and in other studies of upadacitinib. The incidences of any adverse events, serious adverse events, infection and serious infection were numerically higher on upadacitinib 15 and 30 mg than on 7.5 mg. Clinical outcomes were improved and maintained over 260 weeks; Clinical Disease Activity Index clinical remission rates after 5 years were 40.8%, 26.5% and 28.0% on upadacitinib 7.5, 15 and 30 mg, respectively (non-responder imputation). CONCLUSIONS: Upadacitinib showed sustained efficacy with no new safety signals identified through 5 years of treatment and is a long-term treatment option for Japanese patients with rheumatoid arthritis and csDMARDs-IR.