Background/Purpose: Tofacitinib has previously shown efficacy and a manageable safety profile in 12-week (wk) randomized Phase 2 (P2) studies for the treatment of rheumatoid arthritis (RA) in Japan. Here we compare the safety and efficacy of tofacitinib in a long-term extension (LTE) study for Japanese pts with RA who received tofacitinib either as monotherapy or with background methotrexate (bkMTX).
Method: This LTE study (NCT00661661) recruited pts completing P2 studies of tofacitinib either as monotherapy (NCT00687193) or with bkMTX (NCT00603512). LTE pts received tofacitinib 5 mg twice daily (BID) and could change or stop background DMARDs including MTX; inadequate responders could increase to tofacitinib 10 mg BID. For the purposes of this analysis pt groups were defined as follows: pts entering LTE on bk‘MTX' (N=113) or ‘monotherapy' (N=291); pts receiving tofacitinib ‘10 mg BID' for >12 wks (N=66), or all others, i.e. receiving tofacitinib ‘5 mg BID' (N=338).
Result: Results are presented for 404 pts whose tofacitinib exposure ranged from 8 months (mo) through 3 years (y). Efficacy was maintained over the long term in all pts (Figure 1a). Treatment with tofacitinib monotherapy for 1-2 y and with bkMTX for 2-3 y provided similar long-term efficacy. In both populations, the ACR20 response rate was maintained (Figure 1b). In total, 16% (66/404) pts received tofacitinib 10 mg BID for at least 12 wks. An increase in ACR20 response rate was apparent in those pts (Figure 1c).
There was no relationship between length of participation in the study and incidence of adverse events (AEs). Rates of discontinuation (DC) for AEs, DC for serious AEs (SAEs) and DC for serious infections (SIEs) also appeared stable over time (Table).
The most common AEs were infections such as nasopharyngitis (42.8%) and herpes zoster (9.9%). The most common AEs leading to DC were herpes zoster (1.5%), pneumonia (1.0%), and elevations in aspartate aminotransferase (0.5%) and alanine aminotransferase (1.0%) for which the protocol defined 3-fold elevation over the normal range as mandating treatment DC. SIEs were the category of SAEs most frequently leading to DC; the most common SIE was herpes zoster (1.5%).
Conclusion: Tofacitinib demonstrated sustained efficacy in the treatment of Japanese pts with RA when administered as monotherapy for 1-2 y or with bkMTX for 2-3 y. ACR response rates were similar in pts receiving tofacitinib as monotherapy or with bkMTX. The safety profile of tofacitinib, with or without bkMTX, was generally tolerable and consistent with that from P2 studies.
Disclosure: H. Yamanaka, Pfizer Inc, 5 ; Y. Tanaka, Pfizer Inc, 5 ; T. Takeuchi, Pfizer Inc, 5 ; M. Suzuki, Pfizer Inc, 3 ; H. Nakamura, Pfizer Inc, 3 ; Y. Komuro, Pfizer Inc, 3 ; S. Toyoizumi, Pfizer Inc, 3 ; J. D. Bradley, Pfizer Inc, 3 ; S. H. Zwillich, Pfizer Inc, 3, Pfizer Inc, 1 .