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
Open Access
- 18 May 2020
- journal article
- research article
- Published by Wiley in Arthritis & Rheumatology
- Vol. 72 (10), 1621-1631
- https://doi.org/10.1002/art.41316
Abstract
Objective This Phase 2a, 8‐week, double‐blind, parallel‐group study evaluated the efficacy and safety of PF‐06651600 (ritlecitinib), an irreversible inhibitor of Janus kinase 3 (JAK3) and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase family, versus placebo, in patients with rheumatoid arthritis (RA). Methods Seventy patients, seropositive for anticitrullinated protein antibodies and/or rheumatoid factor, were randomized 3:2 to receive oral PF‐06651600 (200 mg once daily [QD]) or placebo for 8 weeks. Patients had an inadequate response to methotrexate and up to 50% could have previously received 1 tumor necrosis factor inhibitor. The primary endpoint was change from baseline in Simple Disease Activity Index (SDAI) score at Week 8, assessed via Bayesian analysis using an informative prior distribution for placebo response. Results Mean change from baseline SDAI score at Week 8, was greater in the PF‐06651600 group (−26.1 [95% credible interval −29.7, −22.4]) versus placebo (−16.8 [−20.9, −12.7]; P < 0.001). Most adverse events (AEs) were mild in severity, and no treatment‐related serious or severe AEs, or deaths were reported. The most common classes of AEs were infections and infestations and skin and subcutaneous tissue disorders; there was one 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 QD) was associated with statistically significant improvements in RA disease activity and was generally well‐tolerated in this small 8‐week study.This publication has 47 references indexed in Scilit:
- Janus kinase inhibitors in autoimmune diseasesAnnals Of The Rheumatic Diseases, 2013
- The influence of ACPA status and characteristics on the course of RANature Reviews Rheumatology, 2012
- American College of Rheumatology/European League Against Rheumatism Provisional Definition of Remission in Rheumatoid Arthritis for Clinical TrialsAnnals Of The Rheumatic Diseases, 2011
- T-Cell Signaling Regulated by the Tec Family Kinase, ItkCold Spring Harbor Perspectives in Biology, 2010
- Selective Inhibition of JAK1 and JAK2 Is Efficacious in Rodent Models of Arthritis: Preclinical Characterization of INCB028050The Journal of Immunology, 2010
- Abatacept, a Novel CD80/86–CD28 T Cell Co‐stimulation Modulator, in the Treatment of Rheumatoid ArthritisBasic & Clinical Pharmacology & Toxicology, 2009
- Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trialThe Lancet, 2008
- Treatment of rheumatoid arthritis with humanized anti–interleukin‐6 receptor antibody: A multicenter, double‐blind, placebo‐controlled trialArthritis & Rheumatism, 2004