Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor approved in the US for the treatment of rheumatoid arthritis at 5 mg BID. Phase (P) 3 studies demonstrated efficacy of tofacitinib and elucidated its safety profile at 5 and 10 mg twice daily (BID). These post‑hoc analyses of pooled P2, P3 and long-term extension (LTE) data assessed whether there were differences in efficacy and/or safety between the patient (pt) populations in the United States (US) and the Rest of World (ROW, non-US).

Methods: Data from DMARD-inadequate responder pts receiving tofacitinib 5 or 10 mg BID ± background nonbiologic DMARDs were pooled from six P2 and five P3 randomized studies and two open-label LTE studies for safety analyses: comparisons evaluated the incidence rates (IRs) (events/100 pt-years) for all tofacitinib groups combined for events of special interest. Pooled P3 data were assessed for efficacy comparisons of tofacitinib 5 and 10 mg BID and placebo (PBO) at Month 3 (PBO could be rescued at Month 3); descriptive statistics are presented.

Results: Data from 664 (US) and 2447 (ROW) pts were included in the efficacy analyses; 974 (US) and 3815 (ROW) pts were included in the safety analyses. Pts in the US and ROW had similar demographics other than a greater proportion of Caucasians seen in the US (PBO, 83.1%; 5 mg BID, 81.1%; 10 mg BID, 82.0%) compared with ROW (PBO, 58.7%; 5 mg BID, 55.3%; 10 mg BID, 55.5%). At Month 3, there were slight differences in the efficacy of tofacitinib between the US and ROW by ACR criteria with the PBO-adjusted response rate very similar for ACR20/50/70 (Table). DAS28-defined remission (DAS28-4(ESR)<2.6) at Month 3 was achieved in numerically more (5 mg) and fewer (10 mg) pts treated with tofacitinib in the US compared with ROW. The HAQ-DI score achieved similar improvement from baseline in the US and ROW. The IRs for safety events in the US and ROW demonstrated numerical differences with higher rates for tuberculosis, herpes zoster (HZ) and lymphoma in ROW compared with the US but higher rates of serious infection events, malignancies and deaths in the US (Table); 95% confidence intervals were largely overlapping. There were no cases of lymphoma or serious HZ in the US.

Conclusion: US study pts achieved similar delta change in ACR responses at both tofacitinib 5 and 10 mg BID in P3 at Month 3 compared with ROW study pts; there was a difference in achieving DAS-defined remission. There were differences seen with respect to safety events of interest, particularly with fewer selected infections of significance in the US. Conclusions are limited by the difference in population sizes.