Safety and efficacy of tofacitinib, an oral Janus kinase inhibitor, up to 36 months in patients with active psoriatic arthritis: data from the second interim analysis of OPAL Balance, an open-label, long-term extension study. Congress of the Pan American League of Associations for Rheumatology (PANLAR), Buenos Aires, Argentina, Apr 201820th Pan American League of Associations for Rheumatology (PANLAR) Meeting (2018)
Objectives: To report the interim data up to January 2017 (database not locked) of the safety, tolerability, and efficacy of tofacitinib for patients (pts) with active PsA from ≤36 months’ participation in an ongoing open-label, long-term extension study (LTE; NCT01976364 OPAL Balance).
Methods: Eligible pts from 2 pivotal Phase (P)3 tofacitinib PsA studies (NCT01877668 OPAL Broaden, NCT01882439 OPAL Beyond) could enter a 3-year LTE ≤3 months after completing the qualifying study or discontinuing for reasons unrelated to the study drug. Pts received tofacitinib 5 mg twice daily (BID) for 1 month, after which an increase to 10 mg BID for efficacy reasons or a reduction back to 5 mg BID for safety reasons was permitted. Pts receiving a csDMARD at entry to a P3 study continued the same csDMARD during the LTE. Primary endpoints were incidence and severity of adverse events (AEs) and change from baseline (Δ) in laboratory values. Efficacy was a secondary objective.
Results: 686 pts were enrolled and treated in OPAL Balance and 530 pts (77.3%) remained at data cut-off. Mean (range) duration of tofacitinib exposure in the LTE was 448 (1–1,015) days. On Day 1, 676 (98.5%) pts received a csDMARD, of which 56 (8.3%) later discontinued. To Month 36, 1,685 AEs were reported in 502 (73.2%) pts, 72 (10.5%) pts had serious AEs, and 52 (7.6%) discontinued due to AEs. AEs of special interest included 11 serious infections (1.6%), 19 herpes zoster events (2.8%) including 1 serious event of facial herpes zoster, 2 major adverse cardiovascular events (0.3%), and 13 (1.9%) malignancies. No AEs of gastrointestinal perforation or inflammatory bowel disease were reported. One AE of uveitis was reported. There were 4 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, and pulmonary embolism. Four AEs of latent tuberculosis were reported in pts whose previously negative QuantiFERON response became positive. Few pts experienced elevated liver enzyme levels; ALT was elevated ≥3x ULN in 20 (2.9%) pts, AST ≥3x ULN in 11 (1.6%) pts. Four (0.6%) pts discontinued due to laboratory value changes: 2 sequential hemoglobin values <8.0 g/dL or decreases >30% from baseline value (n=1); 2 sequential platelet counts <75 x109/L (n=1); 2 sequential AST or ALT elevations ≥5x ULN regardless of total bilirubin or accompanying signs or symptoms (n=1); and 2 sequential increases in serum creatinine >50% and an increase >0.5 mg/dL over average of screening and baseline (n=1). Efficacy was maintained in the LTE, as assessed by ACR20, ACR50, ACR70, ΔHAQ-DI, PASI75, ΔLEI, ΔDSS, and ΔPain.
Conclusions: Over 36 months in the LTE, the safety profile of tofacitinib in pts with active PsA was generally similar to that of the pivotal P3 studies. No new safety signals were identified. Efficacy across various PsA disease domains was maintained over time.
Publication DateApril, 2018
Citation InformationPeter Nash, LC Coates, Alan Kivitz, Philip Mease, et al.. "Safety and efficacy of tofacitinib, an oral Janus kinase inhibitor, up to 36 months in patients with active psoriatic arthritis: data from the second interim analysis of OPAL Balance, an open-label, long-term extension study. Congress of the Pan American League of Associations for Rheumatology (PANLAR), Buenos Aires, Argentina, Apr 2018" 20th Pan American League of Associations for Rheumatology (PANLAR) Meeting (2018)
Available at: http://works.bepress.com/philip-mease/114/