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Efficacy and Safety of PF‐06651600 (Ritlecitinib), a Novel JAK3/TEC Inhibitor, in Patients With Moderate‐to‐Severe Rheumatoid Arthritis and an Inadequate Response to Methotrexate
Author(s) -
Robinson Michael F.,
Damjanov Nemanja,
Stamenkovic Bojana,
Radunovic Goran,
Kivitz Alan,
Cox Lori,
Manukyan Zorayr,
Banfield Christopher,
Saunders Michael,
Chandra Deepa,
Vincent Michael S.,
Mancuso Jessica,
Peeva Elena,
Beebe Jean S.
Publication year - 2020
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.41316
Subject(s) - medicine , rheumatoid arthritis , placebo , gastroenterology , rheumatoid factor , methotrexate , adverse effect , surgery , pathology , alternative medicine
Objective To evaluate the efficacy and safety of PF‐06651600 (ritlecitinib), an irreversible inhibitor of JAK3 and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family, in comparison with placebo in patients with rheumatoid arthritis (RA). Methods An 8‐week, phase II, double‐blind, parallel‐group study was conducted. Seventy patients who were seropositive for anti–citrullinated protein antibodies and/or rheumatoid factor were randomized 3:2 to receive oral PF‐06651600 (200 mg once daily) or placebo for 8 weeks. Eligible patients had an inadequate response to methotrexate, and the study design allowed up to 50% of patients to have previously received 1 tumor necrosis factor inhibitor that was inadequately effective and/or not tolerated. The primary end point was change from baseline in the Simplified Disease Activity Index (SDAI) score at week 8, assessed by Bayesian analysis using an informative prior distribution for placebo response. Results Mean change from baseline in the SDAI score at week 8 was greater in the PF‐06651600 group (−26.1 [95% credible interval −29.7, −22.4]) than in the placebo group (−16.8 [95% credible interval −20.9, −12.7]; P < 0.001). Most adverse events (AEs) were mild in severity, and no treatment‐related serious AEs, severe AEs, or deaths were reported. The most common classes of AE were infections and infestations as well as skin and subcutaneous tissue disorders; there was 1 mild case of herpes simplex in the PF‐06651600 group that was considered to be treatment related, which resolved within 3 days without study treatment discontinuation or antiviral therapy. Conclusion Treatment with the oral JAK3/TEC inhibitor PF‐06651600 (200 mg once daily) was associated with significant improvements in RA disease activity and was generally well‐tolerated in this small 8‐week study.