Two-Year Safety and Effectiveness of Peficitinib in Moderate-To-Severe Rheumatoid Arthritis: A Phase IIb, Open-Label Extension Study

• Published in: Rheumatology and therapy. Vol. 6; no. 4; pp. 503 - 520
• Main Authors: Genovese, Mark C., Greenwald, Maria W., Gutierrez-Ureña, Sergio R., Cardiel, Mario H., Poiley, Jeffrey E., Zubrzycka-Sienkiewicz, Anna, Codding, Christine E., Wang, Annie, He, Weizhong, Amos, Rebecca, Vinueza, Raul, Wang, Xuegong, Garg, Jay P., Kivitz, Alan J.
• Format: Journal Article
• Language: English
• Published: Cheshire Springer Healthcare 01.12.2019; Springer Nature B.V; Adis, Springer Healthcare
• Subjects: Family Medicine; General Practice; Infections; Internal Medicine; Janus kinase (JAK) inhibitor; Long-term extension; Medicine; Medicine & Public Health; Original Research; Orthopedics; Patients; Peficitinib; Quality of Life Research; Rheumatoid arthritis; Rheumatology; Janus kinase (JAK) inhibitor; Long-term extension; Rheumatoid arthritis; Peficitinib
• ISSN: 2198-6576; 2198-6584
• DOI: 10.1007/s40744-019-00167-6

Introduction Peficitinib is a novel orally bioavailable, once-daily Janus kinase (JAK) inhibitor approved in Japan for the treatment of rheumatoid arthritis (RA). This 2-year extension study of two global phase IIb trials investigated the long-term safety and effectiveness of peficitinib. Methods All eligible patients with moderate-to-severe RA including patients in the placebo group who participated in one of two global phase IIb trials (‘with methotrexate’ or ‘without methotrexate’) were included in this 2-year open-label extension study and were converted to peficitinib 100 mg once daily. The primary objective was to evaluate an additional 2 years of safety by assessing treatment-emergent adverse events (AEs) and clinical laboratory evaluations for 105 weeks. Evaluation of an additional 2 years of effectiveness using American College of Rheumatology (ACR) 20/50/70 responses was the exploratory objective. Results Overall, 611 patients were enrolled in the extension study: 319 (52.2%) patients completed the study and 292 (48%) discontinued treatment, including for withdrawal of patient consent ( n  = 96), failure to achieve low disease activity ( n  = 62), and AE not including death ( n  = 41). AEs were reported in 463 (76%) patients. The most common AEs (per 100 patient-years) were upper respiratory tract infections (9.9) and urinary tract infections (7.2). Serious AEs were reported in 80 (13%) patients, with incidences per 100 patient-years of serious infections 2.7, herpes zoster 1.5 (including one herpes zoster ophthalmic), and malignancies 0.6 (most frequently basal cell carcinoma). At week 105, 269 (44%) patients demonstrated an ACR20 response relative to their respective phase IIb trial baselines. Conclusion Among 319 patients who completed this 2-year extension of two global phase IIb studies, peficitinib 100 mg once daily demonstrated a stable safety profile and sustained effectiveness in patients with moderate-to-severe RA. Trial Registration ClinicalTrials.gov identifier, NCT01711814. Registered 19 October 2012. Funding Astellas Pharma Global Development, Inc.