Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). We report the safety, tolerability, and efficacy of tofacitinib in patients (pts) with active PsA from an ongoing, open-label, long-term extension (LTE) study (OPAL Balance, NCT01976364; August 31, 2017 data-cut; study ongoing, database not locked; some values may change in final, locked database).

Methods: Eligible pts from 2 Phase (P)3 tofacitinib PsA studies (OPAL Broaden, NCT01877668; OPAL Beyond, NCT01882439) entered a 3-year LTE ≤3 months after completing the P3 study or discontinuing for reasons other than treatment-related adverse events (AEs). Pts received tofacitinib 5 mg twice daily (BID) to Month (M)1, after which dose adjustments between 5 and 10 mg BID were permitted to improve efficacy, or for safety reasons. Pts receiving a conventional synthetic disease-modifying antirheumatic drug (csDMARD) at P3 study entry continued the same csDMARD in the LTE. Primary endpoints were incidence and severity of AEs, incidence of clinical abnormalities, and changes from baseline (Δ) in laboratory values. Safety data are reported up to M36. Efficacy was evaluated up to M30 (when N>60) as a secondary endpoint.

Results: 686 pts were treated in OPAL Balance; 468 (68.2%) remained in the study at data cut-off. Mean (range) LTE tofacitinib treatment duration was 614 (1–1,032) days. On Day 1, 675 pts (98.4%) received a csDMARD, which was discontinued in 86 pts (12.7%). To M36, 2,189 AEs were reported in 546 pts (79.6%), 95 pts (13.8%) had serious AEs, and 59 pts (8.6%) discontinued due to AEs. Serious infections occurred in 12 pts (1.7%), herpes zoster in 20 pts (2.9%; 1 serious event), major adverse cardiovascular events in 5 pts (0.7%), malignancies in 24 pts (3.5%; including 12 pts with non-melanoma skin cancer), and uveitis in 2 pts (0.3%). No AEs of gastrointestinal perforation or inflammatory bowel disease were reported. There were 5 deaths (not attributed to treatment, as assessed by the investigator) due to metastatic pancreatic carcinoma, acute cardiac failure/hypertensive heart disease, chronic obstructive pulmonary disease, pulmonary embolism, and cardiovascular insufficiency. Four AEs of latent tuberculosis were reported in pts whose previously negative QuantiFERON response became positive. Alanine aminotransferase was elevated ≥3x the upper limit of normal (ULN) in 27 pts (4.0%), and aspartate aminotransferase ≥3x ULN in 15 pts (2.2%). Changes in laboratory values observed in P3 studies were generally stable in the LTE, except for a modest decrease in absolute lymphocyte count over time. Eight pts (1.2%) discontinued (protocol-mandated) due to laboratory value changes. ACR responses, ΔHealth Assessment Questionnaire-Disability Index, Psoriasis Area and Severity Index ≥75% improvement response, ΔLeeds Enthesitis Index, ΔDactylitis Severity Score, and ΔPain were maintained up to M30.

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