Tofacitinib (CP-690,550), un inhibidor de la quinasa Janus oral, como monoterapia en pacientes japoneses con artritis reumatoide activa: Un estudio de 12 semanas de fase 2b

BACKGROUND/PURPOSE:

To compare efficacy, safety, and tolerability of 5 doses of tofacitinib monotherapy vs placebo (PBO) for treatment of rheumatoid arthritis (RA) in Japanese pts with inadequate response to DMARDs.

METHODS:

This study was a 12-week (wk), double-blind, PBO-controlled Phase 2b study. Pts with active RA (>=6 tender/swollen joints, C-reactive protein [CRP] >7 mg/L or ESR > upper limit of normal [ULN]) were randomized to tofacitinib 1, 3, 5, 10, 15 mg twice daily (BID) or PBO. Continuation of stable doses of NSAIDs and corticosteroids <=10 mg prednisone equivalent was permitted.

RESUTLS:

317 pts received at least one dose of study medication. Baseline demographics and disease characteristics were comparable across treatment groups: mean ages were 52.6 to 54.7 years (y); mean duration of RA was 6.4 to 11.0 y; mean tender joint count was 13.6 to 18.6; mean swollen joint count was 11.3 to 15.3; mean DAS28-4(ESR) was 5.9 to 6.4. The primary endpoint, ACR20 response rate at Wk 12, was statistically superior for all tofacitinib doses compared with PBO and a clear dose-response was observed. ACR50 and ACR70 response rates at Wk 12 also showed a dose-response. Tofacitinib dosed >=5 mg BID was statistically superior in rates of DAS28-4(ESR) <2.6 at Wk 12 with maximum effect observed at doses of 10 mg and 15 mg BID.

CONCLUSION:

When used as monotherapy, tofacitinib dosed >1 mg BID demonstrated superior ACR20 response rates compared with PBO at Wk 12. Doses of tofacitinib 5, 10, and 15 mg BID demonstrated superiority to placebo in DAS28-4(ESR) < 2.6. The safety profile of tofacitinib monotherapy was manageable in Japanese pts with long-standing active RA.