Safety and efficacy of tofacitinib, an oral Janus kinase inhibitor, in patients with active psoriatic arthritis: Interim data from OPAL Balance, an open label, long-term extension study

Background: Tofacitinib is an oral Janus kinase inhibitor under investigation for treatment of psoriatic arthritis (PsA). We report April 4, 2016 interim data (database not locked; data may change) from patients (pts) with PsA participating;15 months in an ongoing open-label, long-term extension study (LTE; NCT01976364 OPAL Balance) to evaluate safety and efficacy of tofacitinib. Methods: Pts from the 2 pivotal phase 3 tofacitinib PsA studies (NCT01877668 OPAL Broaden, NCT01882439 OPAL Beyond) were invited to enter a 3 year LTE within 3 months of completing or discontinuing (non-study drug related) the parent study. Pts initially received tofacitinib 5mg twice daily (BID). Dose increase to 10 mg BID and reduction back to 5 mg BID was permitted for efficacy and safety reasons. Primary endpoints: incidence and severity of adverse events (AEs) and changes in laboratory values. Long-term efficacy was a secondary endpoint. Results: Of 685enrolled pts, 680were treated, and 608(89.4%) persisted at data cut-off. Mean (range) tofacitinib exposure was 206 (3-741) days. In the LTE, 367 (54.0%) pts reported 860 AEs; 41 (6.0%) pts had serious AEs and 3 pts died (not treatment-related). 6 serious infections and 10 herpes zoster cases were reported. 2 opportunistic infections, 2major adverse cardiovascular events, and 2malignancies were adjudicated as meeting criteria. No cases of gastrointestinal perforation, inflammatory bowel disease, or uveitis were reported. 1 ptmet discontinuation criteria for serumcreatinine increase>50% and>0.5 mg/dL over the average of screening and baseline values. Increases from parent study baseline in high- and low-density lipoprotein cholesterol were reported (mean [SD] % change to Month 12: 7.6 [20.1] and 12.2 [29.9], respectively), and 18 (2.6%) pts started new lipid-lowering drugs in the LTE. Efficacy observed in the parent studies was maintained in the LTE; Month 15 response rates: American College of Rheumatology (ACR)20, 72.7% (N=66); ACR50, 47.0% (N=66); ACR70, 28.4% (N = 67); PASI75, 68.9% (N = 45); Health Assessment Questionnaire e Disability Index decrease from baseline ≥0.35 (MCID), 55.7% (N = 61). Conclusion: Over 15 months, the safety profile of tofacitinib in pts with active PsA was generally similar to that reported in the pivotal Phase 3 studies. No new safety risks were identified vs previous tofacitinib studies in rheumatoid arthritis or psoriasis. Efficacy observed in OPAL Beyond and OPAL Broaden was maintained in the LTE.