Efficacy of VX-509 (decernotinib) in Combination with a Disease-modifying Antirheumatic Drug in Patients with Rheumatoid Arthritis: Clinical and MRI Findings
This Phase 2b study of VX-509 (decernotinib), a selective JAK3 inhibitor, showed that VX-509 in combination with stable DMARD therapy was effective for improving synovitis and osteitis as assessed by MRI in patients who had an inadequate response to DMARD therapy.
Patients were randomised to treatment groups receiving either placebo, VX-509 100 mg, 200 mg or
300 mg for 12 weeks. Minimum inclusion criteria included Grade ≥2 clinical synovitis in either the wrist or two metacarpophalangeal joints. ACR20, change in DAS28-CRP, and change in RAMRIS scores from baseline to Week 12 were the primary endpoints. For MRI examination, the hand with the highest number of clinically swollen joints was chosen.
At Week 12, a greater percentage of patients receiving VX-509 achieved ACR20, ACR50 and ACR70 across all doses versus placebo. However, only the 300 mg group achieved significant differences versus placebo, for ACR50 (P<0.05).
A dose-dependent reduction in the change from baseline for DAS28-CRP and -ESR was seen, with statistically significant reductions achieved in the 200 mg and 300 mg groups. The RAMRIS scores for synovitis and osteitis also showed dose-dependent results and significant results across all VX-509 treatment groups for synovitis (P<0.01), and the 300 mg group for osteitis. The significant improvements from baseline in RAMRIS scores for synovitis with VX-509 200 and 300 mg, and for osteitis with VX-509 300 mg, provide objective documentation of the effect of VX-509 on inflammation in the synovium
No new safety concerns developed and an AE profile was shown similar to that previously seen in other Phase 2 studies for VX-509.