A Phase 2b Study of ABT-494, a Selective JAK1 Inhibitor, in Patients With Rheumatoid Arthritis and an Inadequate Response to Anti–TNF Therapy

Objective: To compare the efficacy and safety of ABT-494, a novel selective Janus kinase 1 inhibitor, with placebo, in patients with moderate-to-severe rheumatoid arthritis (RA) and an inadequate response or intolerance to ≥1 anti–tumor necrosis factor (TNF) therapy. Methods: In this 12-week, double-blind, placebo-controlled, dose-ranging study, 276 patients with ≥1 prior anti-TNF therapy on a stable methotrexate dose were randomized equally to immediate-release ABT-494 3, 6, 12, or 18 mg twice daily or placebo. The primary endpoint was the proportion of patients achieving an ACR20 response at Week 12. Results: At Week 12, significantly more patients in the ABT-494 groups (53-71%) versus placebo (34%) achieved an ACR20 response (NRI, P<0.05), with a dose-response relationship among all ABT-494 doses (P