Baricitinib versus placebo or adalimumab in rheumatoid arthritis

Background Baricitinib is an oral, reversible, JAK1/JAK2 inhibitor that may have therapeutic value in patients with rheumatoid arthritis. Methods In this 52-week, phase 3, double-blind, placebo and active-controlled study, 1307 patients with active rheumatoid arthritis receiving background methotrexate were randomized 3:3:2 to placebo (switched to baricitinib after 24 weeks), baricitinib 4-mg once daily, or anti-tumor necrosis factor α monoclonal antibody, adalimumab, 40-mg every other week. Endpoint measures controlled for multiplicity included American College of Rheumatology 20% response (ACR20, primary endpoint), 28-joint Disease Activity Scores (DAS28), Health Assessment Questionnaire-Disability Index (HAQ-DI), and Simplified Disease Activity Index (SDAI) at Week 12, and progressive radiographic joint damage as measured by van der Heijde modified Total Sharp score (mTSS) at Week 24. Results More patients achieved an ACR20 response at Week 12 with baricitinib than placebo (primary objective, 70% vs. 40%, P≤0.001). All major secondary objectives were met, including inhibition of progressive radiographic joint damage (mTSS, range 0 to 448, with higher scores indicating greater damage) at Week 24 for baricitinib vs. placebo (mean change from baseline 0.41 vs.0.90, P≤0.001) and increased ACR20 response rate at Week 12 for baricitinib vs. adalimumab (70% vs. 61%, P=0.014). Adverse events, including infections, were more frequent through Week 24 for baricitinib and adalimumab compared to placebo. Malignancies were reported in 5 patients (2 baricitinib, 3 placebo). Baricitinib was associated with reductions in neutrophils and increases in creatinine and low-density lipoprotein cholesterol. Conclusions In patients with rheumatoid arthritis with inadequate response to methotrexate, baricitinib was associated with significant clinical improvements compared to placebo and adalimumab