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<0.001). ACR50/70 response rates were significantly higher in the ABT-494 groups (35-42% and 22-26%) versus placebo (ACR50, 16% and ACR70, 4%). Changes in DAS28(CRP) [ΔDAS28(CRP)] were significantly greater for all doses of ABT-494 versus placebo (P≤0.001). Onset of action was rapid, with significant differences versus placebo at Week 2, in ACR20 and ΔDAS28(CRP) (P≤0.001 for 6-18 mg). The most frequent AEs were headache, nausea, upper respiratory and urinary tract infections. Infection rates were higher at higher doses of ABT-494, but none were serious. No deaths were reported on ABT-494. Conclusions: In patients with an inadequate response or intolerance to anti-TNF therapy, ABT-494 added onto methotrexate showed rapid, dose-dependent improvements in RA signs and symptoms, with similar safety and tolerability to drugs of this class. No new AEs were identified.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)