Background/Purpose:   VX-509 is an oral JAK3 inhibitor being evaluated as a treatment for RA. Safety and efficacy results from a phase 2a, 12-week, randomized placebo-controlled trial (RCT) in patients with active rheumatoid arthritis (RA) who had failed ≥ 1 DMARD have been reported previously. The objective was to assess impact of treatment with VX-509 on patient-reported outcomes (PRO) during the RCT.

Methods: Patients were randomized to treatment groups that received 1 of 4 doses of VX-509 (25, 50, 100, or 150 mg BID) or placebo BID as monotherapy for 12 weeks. PRO assessments included the Health Assessment Questionnaire-Disability Index (HAQ-DI), visual analog scale (VAS) assessments of patient’s general health (subject general health; PtGH) and pain, and the Short Form 36 Health Survey (SF-36). Least squares (LS) mean changes from baseline (BL) were obtained for each group and significance testing versus placebo was conducted using a mixed-effects model for repeated measures analysis. The percentages of patients reporting clinically meaningful improvements (Minimal Clinically Important Differences; MCID) for each PRO are reported, using non-responder imputation for early terminations or incomplete data. In addition, the Cochran-Armitage test was conducted to assess trends in the MCID data across dose groups.

Results: 204 patients were randomized to treatment groups and received at least 1 dose of study drug. Patients receiving 50, 100, and 150 mg BID VX-509 reported significant (all p<0.01) and clinically meaningful improvements in PtGH, pain, HAQ-DI, and SF-36 Physical Component Score (PCS) at week 12 (Table).

Conclusion: In this phase 2a clinical study of patients with RA, VX-509 administered as monotherapy resulted in meaningful improvements in PROs, suggesting that VX-509 treatment may result in benefits to patients beyond traditional efficacy measures.