Background/Purpose: Tofacitinib is an oral JAK inhibitor for the treatment of RA. Open-label, long-term extension (LTE) studies enrolled tofacitinib-treated patients (pts) to evaluate safety and efficacy over time. The time on treatment is considered a composite measure of efficacy and safety, as discontinuation (D/C) is often due to lack of efficacy (LOE) and/or adverse events (AEs) for DMARDs. This analysis estimated drug survival of tofacitinib up to 96 months (mo; 8 years) in LTE studies and describes reasons for D/C.

Methods: Data were pooled from 2 LTE studies (NCT00413699 [ongoing; database unlocked at March 2015 data-cut] and NCT00661661) of pts with RA who had participated in Phase (P) 1/2/3 tofacitinib studies. Of the 6570 pts from P1/2/3 studies, 4867 pts (74.1%) received treatment in LTE studies. Pts received tofacitinib 5 or 10 mg BID as monotherapy or with background DMARDs. Assignment to tofacitinib dose group in this analysis was based on the average daily dose in LTE. Kaplan-Meier analyses estimated drug survival in pts who withdrew for any reason, due to LOE or due to AEs in the LTE, including pts who had previously responded to and tolerated treatment in P1/2/3 studies. Ongoing pts were censored as of March 2015, while pts completing the trial(s) were censored at their completion date. Data are included over 96 mo. Retention data were analyzed by dose, mono vs combination therapy, and baseline characteristics.

Results: 4867 pts were treated for a mean (maximum) duration of 3.0 (7.9) years (yrs) in the LTE. Overall, the median survival for all tofacitinib-treated pts in the LTE was 5.0 yrs [95% CI 4.7, 5.2]; for pts receiving tofacitinib with background DMARDs was 4.9 [4.5, 5.2] yrs and as monotherapy was 5.1 [4.6, 5.9] yrs. Similar survival was observed between doses: median survival was 5.2 [4.8, 5.7] and 4.8 [4.5, 5.2] yrs for 5 and 10 mg BID, respectively. The D/C rate due to LOE was considerably lower than due to AEs (LOE: 3.1%, 3.5%, 3.0%; AEs: 21.6%, 25.2%, 20.0% for all tofacitinib, 5 or 10 mg BID, respectively). The most commonly reported reasons for D/C due to AEs by system organ class were infections/infestations (8.8%, 8.5%, 8.9%), investigations (4.2%, 5.6%, 3.5%) and neoplasms (benign, malignant, unspecified) (3.2%, 4.4%, 2.8%) for all tofacitinib, 5 or 10 mg BID, respectively. Overall, median survival was generally similar for pts receiving all tofacitinib, 5 and 10 mg BID across selected baseline characteristics (tofacitinib 5 mg BID, Table; tofacitinib all and 10 mg BID, data not shown).

Conclusion: Drug survival in LTE studies provides important information on the long-term safety, efficacy, and tolerability of a therapy. Median survival of tofacitinib was ~5 yrs, with D/C more commonly associated with AEs than LOE. Similar survival was observed for the 5 and 10 mg BID dose groups, for mono vs combination therapy, and across selected baseline characteristics. These data support the use of tofacitinib for long-term RA management.