Results from phase IIb trial on efficacy and safety of brepocitinib for treating psoriatic arthritis

Brepocitinib is an oral medication that inhibits the tyrosine kinase 2 (TYK2) and Janus kinase 1 enzymes involved in inflammation. It is currently being evaluated for the treatment of numerous immunological diseases. Brepocitinib 30 and 60 mg QD reduced psoriatic arthritis (PsA) symptoms and indicators more effectively than the placebo, according to new findings of Dr. Mease and his colleagues that was published in Arthritis & Rheumatology.

Brepocitinib 10 mg once daily (QD), 30 mg QD, 60 mg QD, or placebo was given to 218 participants in this placebo-controlled, dose-ranging, phase IIb research. At week 16, brepocitinib 30 or 60 mg QD groups substantially outperformed the placebo (43.3%) in terms of American College of Rheumatology (ACR)20 response rates (66.7% [P = 0.0197] and 74.6% [P = 0.0006]), as well as ACR50/70, Psoriasis Area and Severity Index (PASI75/90), and Minimal Disease Activity (MDA) response rates. Through week 52, response rates were either sustained or increased. The study reported mild to moderate severity of adverse events in 2.8% and 5.5% of participants who received brepocitinib at 30 and 60 mg QD. There were no significant fatal cardiovascular incidents or injuries.

In a review published in 2023 by Dr. George Martin reported that brepocitinib and ropsacitinib as the two TYK2 inhibitors in lateral clinical-stage development. This review described the mechanism of deucravacitinib, ropsacitinib, and brepocitinib. While ropsacitinib and brepocitinib are orthosteric inhibitors that bind to the catalytic domain and inhibit TYK2 and at least one other Janus kinase, deucravacitinib binds in an allosteric manner to specifically inhibit TYK2. In conclusion, the review declares that a phase 2 trial is investigated to compare ropsacitinib with brepocitinib in patients with moderate-to-severe hidradenitis suppurativa, even though ropsacitinib is not presently being explored in PsA. Moroever, the effectiveness of oral brepocitinib in treating active PsA, active non-segmental vitiligo, moderate-to-severe systemic lupus erythematosus, Crohn’s disease, and ulcerative colitis, as well as topical brepocitinib in treating mild-to-moderate atopic dermatitis, is being investigated in clinical studies. 

Brepocitinib has shown to be effective and safe when used in people with moderately to severely active PsA. In addition to improving the optimal positioning of TYK2 inhibitors in the arsenal of therapeutic options for PsO and PsA, longer-term efficacy and safety studies will also be beneficial.

References

  1. Mease P, Helliwell PS, Silwinska-Stanczyk P, Miakisz M, Ostor A, Peeva E, Vincent M, Sikirica V, Winnette R, Qiu R, Li G. Efficacy and safety of brepocitinib (tyrosine kinase 2/janus kinase 1 inhibitor) for the treatment of active psoriatic arthritis: results from a phase 2b randomized controlled trial. ARTHRITIS & RHEUMATOLOGY. 2021;73:1009-11.
  2. Martin G. Novel Therapies in Plaque Psoriasis: A Review of Tyrosine Kinase 2 Inhibitors. Dermatology and Therapy. 2023 Jan 2:1-9.