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Background/Purpose: To compare the efficacy, safety, and tolerability of tofacitinib monotherapy for the treatment of rheumatoid arthritis (RA) in Japanese (J) and global (G) pts with an inadequate response to DMARDs.
Method: This was a planned comparison of J and G Phase 2 studies of tofacitinib monotherapy. The J study randomized 318 pts; the G study was conducted outside Japan and randomized 384 pts. Both were randomized, double-blind, placebo (PBO) controlled studies of tofacitinib 1, 3, 5, 10, and 15 mg twice daily (BID) enrolling pts with active RA (≥6 tender and swollen joints at baseline). The G study also included an active comparator arm and ran for 24 weeks (wks) in total. Inclusion and exclusion criteria and primary endpoints (ACR20 response rates at Wk 12) were matched to permit comparison. For the primary endpoint, a pair-wise Chi-Square Test with a 2‑sided significance level of 0.05 was used to compare tofacitinib 1, 3, 5, 10, and 15 mg BID with PBO; type 1 error was protected using a step-down procedure in each study.
Result: In both studies the mean ages and durations of RA were similar. In contrast, the range of mean body weight was lower for J (52.9 to 57.4 kg) than G pts (65.7 to 75.7 kg). There were differences in baseline (pre-treatment) number of tender joints (J: 13.6-18.6 vs G: 24.1-27.1) but there was no major difference in DAS28-4(ESR) (J: 5.87-6.42 vs G: 6.30-6.57).
ACR20, ACR50, and AC70 response rates were dose-dependent in both studies and the dose response was similar across studies, although absolute response rates were higher in Japan (Figure).
The incidence of adverse events (AEs) was 44.2% (PBO), 55.5% (5 mg BID), 60.4% (10 mg BID), and 51.9% (15 mg BID) in the J study and 40.7% (PBO), 49.0% (5 mg BID), 50.8% (10 mg BID), and 52.6% (15 mg BID) in the G study. Categories of AEs occurring at an incidence of ≥10% were gastrointestinal disorders, infections and infestations, investigations, metabolism and nutritional disorders, nervous system disorders, skin and subcutaneous tissue disorders; the incidence rates of AEs were similar between the studies. Serious AEs were infrequent and had no apparent relationship to tofacitinib dose (Table).
Dose-dependent decreases in neutrophil counts, dose-dependent increases in total, high and low density lipoprotein cholesterol and small increases in serum creatinine were observed in both studies (Table). Overall, the safety profiles in the two studies were similar.
Conclusion: The efficacy dose-response and safety of tofacitinib monotherapy at 12 wks was similar in J and G pts.
Disclosure: T. Takeuchi, Pfizer Inc, 5 ; Y. Tanaka, Pfizer Inc, 5 ; H. Yamanaka, Pfizer Inc, 5 ; M. Suzuki, Pfizer Inc, 3 ; H. Nakamura, Pfizer Inc, 3 ; K. Yazawa, Pfizer Inc, 3 ; S. Toyoizumi, Pfizer Inc, 3 ; J. D. Bradley, Pfizer Inc, 3 ; S. H. Zwillich, Pfizer Inc, 3, Pfizer Inc, 1 .