Efficacy and safety of tofacitinib in Japanese patients with rheumatoid arthritis by background methotrexate dose: a post-hoc analysis of clinical trial data.

OBJECTIVES: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). We investigated concomitant methotrexate (MTX) dose on tofacitinib efficacy/safety in Japanese RA patients.

METHODS: This post-hoc analysis pooled data from a 3-month Phase 2 study (NCT00603512) and a 24-month Phase 3 study (NCT00847613). Patients (N = 254) received tofacitinib (low-dose [1 or 3 mg], 5 mg, 10 mg) twice daily (BID) or placebo, with low-dose (>0-≤8 mg/week) or high-dose (>8 mg/week) MTX. Efficacy (ACR20/50/70 and DAS28-4[ESR] < 2.6 response rates; changes from baseline [CFB] in DAS28-4[ESR] and HAQ-DI) and safety (adverse events [AEs], discontinuations due to AEs, serious AEs, and deaths) were assessed through Month 3.

RESULTS: At Month 3, ACR20/50/70 response rates, mean DAS28-4(ESR) CFB and HAQ-DI CFB were similar across MTX doses and generally greater for all tofacitinib doses versus placebo. AE rates with low-dose/high-dose MTX were: placebo, 28.6%/52.9%; tofacitinib low-dose, 50.0%/66.7%; 5 mg BID, 56.5%/64.3%; 10 mg BID, 73.8%/67.7%.

CONCLUSIONS: Tofacitinib efficacy in Japanese RA patients may be unaffected by background MTX dose. AE rates with low-dose versus high-dose MTX were lower with placebo, tofacitinib low-dose or 5 mg BID, but not 10 mg BID, with no apparent differences across system organ class/laboratory parameters.