Arthritis Rheumatol. 2016 Jan;68(1):46-55.VX-509 (decernotinib) is a novel oral, selective inhibitor of JAK-3. JAK-3 is a member of the JAK signalling family that is primarily expressed in hematopoietic cells and associates with only the common γ-chain making it a promising therapeutic drug target. A phase IIb 24-week study of VX-509 in 358 patients with RA, who had prior inadequate response to MTX, uses ACR20 response rate and DAS28-CRP change at Week 12 to assess the efficacy of VX-509. Patients were administered either placebo+MTX or VX-509+MTX in dosages of 100 mg/day, 150 mg/day, 200 mg/day, or 100 mg BID.At Week 12, VX-509 demonstrated statistically significantly improvements in signs and symptoms of RA compared with placebo, and improvements were maintained through Week 24. The most common adverse event in the VX-509 groups were headache. Elevated levels of transaminases, lipoproteins, and creatinine were also observed. This study provides evidence for VX-509 in combination with MTX as effective in reducing the signs and symptoms of RA in patients with inadequate response to MTX.