Safety and efficacy of tofacitinib, an oral janus kinase inhibitor, up to 36 months in patients with active psoriatic arthritis: data from the third interim analysis of opal balance, an open-label, long-term extension study

Abstract

Aim Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). We report tofacitinib safety, tolerability and efficacy in active PsA patients from an open‐label extension (LTE) study (OPAL Balance; NCT01976364; November 2017 data‐cut; database not locked).

Method Eligible patients from 2 Phase (P)3 tofacitinib PsA studies (OPAL Broaden; OPAL Beyond) entered a 3‐year LTE. Patients received tofacitinib 5 mg BID to Month (M)1, after which dose adjustments between 5 and 10 mg BID were permitted to improve efficacy, or for safety reasons. Patients receiving a csDMARD at P3 study entry continued the same csDMARD in the LTE. Primary endpoints: incidence and severity of adverse events (AEs) through M36; change from baseline (Δ) in laboratory values. Efficacy was evaluated through M30 (when N>50).

Result 686 patients were treated in OPAL Balance; 468 (68.2%) remained in the study at data cut‐off. Mean (range) LTE tofacitinib exposure was 614 (1–1032) days. To M36, 2189 AEs were reported in 546 patients (79.6%); 95 (13.8%) had serious AEs; 59 (8.6%) discontinued due to AEs. Serious infections occurred in 12 patients (1.7%), herpes zoster in 20 (2.9%), major adverse cardiovascular events in 5 (0.7%), malignancies in 24 (3.5%; including 12 NMSC) and uveitis in 2 (0.3%). No gastrointestinal perforations or inflammatory bowel disease were reported. There were 5 deaths, all unrelated to study drug (investigator‐determined). ALT ≥3x ULN occurred in 27 patients (4.0%); AST ≥3x ULN in 15 (2.2%). Eight patients (1.2%) discontinued (protocol‐mandated) due to laboratory changes. ACR responses, ΔHAQ‐DI, PASI75 response, ΔLEI, ΔDSS and ΔPain were maintained through M30.

Conclusions Over 36 months in the LTE, the safety profile of tofacitinib in active PsA patients was generally similar to that of P3 studies. No new safety risks were identified. Efficacy was maintained over time across various PsA disease domains.