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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

Rheumatol. 2020 May 18. doi: 10.1002/art.41316. Online ahead of print.

Michael F Robinson 1, Nemanja Damjanov 2, Bojana Stamenkovic 3, Goran Radunovic 2, Alan Kivitz 4, Lori Cox 5, Zorayr Manukyan 6, Christopher Banfield 6, Michael Saunders 6, Deepa Chandra 5, Michael S Vincent 5, Jessica Mancuso 7, Elena Peeva 5, Jean S Beebe 5

Author Information

1 California Medical Research Associates, Northridge, CA, USA.

2 Institute of Rheumatology, Belgrade University School of Medicine, Belgrade, Serbia.

3 Rheumatology Clinic, Institute for Treatment and Rehabilitation Niska Banja, Nis University School of Medicine, Nis, Serbia.

4 Altoona Center for Clinical Research, Duncansville, PA, USA.

5 Inflammation and Immunology Research Unit, Pfizer Inc, New York, NY, USA.

6 Early Clinical Development Unit, Pfizer Inc, New York, NY, USA.

7 Early Clinical Development Unit, Pfizer Inc, Groton, CT, USA.

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.