Efficacy and Safety of Tyrosine Kinase 2/Janus Kinase 1 Inhibitor Brepocitinib for Active Psoriatic Arthritis: A Phase IIb Randomized Controlled Trial.

Abstract

Brepocitinib is a tyrosine kinase 2/Janus kinase 1 inhibitor in development for treatment of several immunological diseases. Efficacy and safety of oral brepocitinib were assessed in participants with moderately-to-severely active psoriatic arthritis (PsA) for up to 52 weeks. This placebo-controlled, dose-ranging, phase IIb study randomized participants to brepocitinib 10 mg once daily (QD), 30 mg QD, 60 mg QD, or placebo, advancing to brepocitinib 30 or 60 mg QD at week 16. The primary endpoint was American College of Rheumatology (ACR)20 response rate at week 16. Secondary endpoints included response rates of ACR50/70, 75% and 90% improvement in Psoriasis Area and Severity Index (PASI75/90), and Minimal Disease Activity (MDA) at weeks 16 and 52. Adverse events (AEs) were monitored throughout. Overall, 218 participants were randomized and treated. At week 16, brepocitinib 30 and 60 mg QD groups had significantly greater ACR20 response rates (66.7% [P = 0.0197] and 74.6% [P = 0.0006], respectively), versus placebo (43.3%) and significantly higher ACR50/70, PASI75/90, and MDA response rates. Response rates were maintained or improved through week 52. AEs were mostly mild/moderate; serious AEs (15) in 12 (5.5%) participants included infections in 6 (2.8%) in brepocitinib 30 and 60 mg QD groups. No major adverse cardiovascular events or deaths occurred. Brepocitinib 30 and 60 mg QD were superior to placebo at reducing signs and symptoms of PsA. Brepocitinib was generally well tolerated throughout the 52-week study with a safety profile consistent with other brepocitinib clinical trials.