Upadacitinib in Rheumatoid Arthritis and Inadequate Response to Conventional Synthetic Disease-Modifying Antirheumatic Drugs: Efficacy and Safety Through 5 Years (SELECT-NEXT).

Abstract

To report 5-year efficacy and safety of upadacitinib in rheumatoid arthritis (RA) from the phase 3 long-term extension (LTE) of SELECT-NEXT. Patients on stable conventional synthetic disease-modifying antirheumatic drugs were randomized to upadacitinib 15 mg, upadacitinib 30 mg once daily (UPA15/30), or placebo for 12 weeks. Following this, placebo-randomized patients were switched to UPA15 or UPA30 in the LTE; upadacitinib-randomized patients continued their original dose. Blinding remained until dose switching from UPA30 to UPA15 due to approval of UPA15; the earliest switch occurred at week 168. Efficacy (as observed) and treatment-emergent adverse events (TEAEs) are reported through 5 years. Overall, 611 (92%) randomized patients entered the LTE; 271 (44%) discontinued study drug by 5 years, primarily due to adverse events (16%). Clinical outcomes improved or were maintained at 5 years; 51% and 43% of patients achieved Clinical Disease Activity Index remission and 75% and 66% achieved 28-joint Disease Activity Score-C-reactive protein < 2.6 among those initially randomized to UPA15 and UPA30, respectively. Proportions of patients achieving ≥ 20/50/70% improvement in American College of Rheumatology criteria responses increased from week 60 through 5 years. Results were similar regardless of initial randomization to upadacitinib or placebo. TEAEs, including TEAEs of special interest, were consistent with earlier analyses and other SELECT studies. Malignancies (excluding non-melanoma skin cancer), major adverse cardiovascular events, and venous thromboembolic events were reported infrequently. No new safety signals were observed. The 5-year benefit-risk profile for upadacitinib in RA remains favorable.