Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial

Abstract

Background Upadacitinib is a selective inhibitor of Janus kinase 1 and was efficacious in phase 2 studies in patients with moderate-to-severe rheumatoid arthritis. We aimed to assess the efficacy of upadacitinib in patients with inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Methods This study is a double-blind, placebo-controlled trial at 150 sites in 35 countries. We enrolled patients aged 18 years or older with active rheumatoid arthritis for 3 months or longer, who had received csDMARDs for at least 3 months with a stable dose for at least 4 weeks before study entry, and had an inadequate response to at least one of the following csDMARDs: methotrexate, sulfasalazine, or leflunomide. Using interactive response technology, we randomly assigned patients receiving stable background csDMARDs (2:2:1:1) to receive a once-daily extended-release formulation of upadacitinib 15 mg or 30 mg, or placebo, for 12 weeks. Patients, investigators, and the funder were masked to allocation. After 12 weeks, patients taking placebo received 15 mg or 30 mg of upadacitinib once daily, according to the prespecified randomisation assignment. The primary endpoints were the proportion of patients at week 12 who achieved 20% improvement in American College of Rheumatology criteria (ACR20), and a 28-joint disease activity score using C-reactive protein (DAS28[CRP]) of 3·2 or less. We did efficacy analyses in the full analysis set of all randomly assig…