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The oral selective inhibitor showed significant benefit versus placebo at 2 different doses in the phase 2b trial.
Small-molecule tyrosine kinase 2/Janus kinase 1 (TYK2/JAK-1) inhibitor brepocitinib provided significant benefit for patients with active psoriatic arthritis while also providing a safety profile similar to that observed with other regulated JAK inhibitors, according to new findings presented at the American College of Rheumatology (ACR) 2021 Convergence this week.
In new phase 2b data presented by Philip J. Mease, MD, the oral investigative selective inhibitor therapy being developed by Pfizer showed adult patient improvement in multiple clinical outcomes for psoriatic arthritis, as well as quality-of-life measures, at 2 different dose rates.
Mease, a Clinical Professor at the University of Washington School of Medicine and Director of Rheumatology Research at the Swedish Medical Center, and colleagues sought to follow “promising results” of brepocitinib in assessment for the treatment of plaque psoriasis, alopecia areata, and psoriatic arthritis.
They conducted a randomized, placebo-controlled trial comparing the efficacy and safety of once-daily brepocitinib pills at 3 different doses—10, 30, and 60 mg—versus placebo in adult patients with psoriatic arthritis. Eligible patients were aged 18 to 75 years old, met Classification Criteria for Psoriatic Arthritis (CASPAR), and had active disease regardless of treatment or intolerance to non-steroidal anti-inflammatory drugs (NSAIDs) or disease-modifying antirheumatic drugs (DMARDs).
During the efficacy and safety assessment, patients were allowed stable doses of conventional synthetic DMARDs; another 30% of patients with prior use of TNF inhibitors were allowed to continue treatment. Mease and colleagues randomized 218 patients 2:2:1:2 to brepoctinib 60 mg, 30 mg, 10 mg, or placebo, for 16 weeks; patients in treatment arms were advanced to brepocitinib 30 or 60 mg once-daily from weeks 16 to 52.
Investigators sought a primary endpoint of amount of patients meeting ACR20 response at 16 weeks, with a multitude of efficacy and safety endpoints.
Approximately 93% of patients completed the trial through week 16. At that time, Mease and colleagues observed that a significantly greater proportion of patients in the 30 mg and 60 mg brepocitinib groups achieved ACR20 response versus placebo. The same treatment arms additionally reported significant improvements in the following outcomes:
Both treatment arms additionally showed improvement or sustainment for dactylitis and Spondyloarthritis Research Consortium of Canada enthesitis resolution from week 16 to week 52.
More patients treated with 30 mg (n = 33) or 60 mg (n = 40) brepocitinib reported adverse events than patients on placebo (n = 32) at 16 weeks—however, a majority of events (n = 165 [66%]) were mild in severity. Investigators did observe 17 serious adverse events among 12 patients through the phase 2b trial. That said, they defined the overall safety profile of the investigative drug at 52 weeks to be consistent with that of other JAK inhibitors; serious events included herpes zoster infections and changes in prespecified lab parameters. Investigators observed no major cardiovascular or venous thromboembolic events, nor deaths, among treated patients.
Mease and colleagues concluded that brepoctinib demonstrated “superior efficacy across numerous psoriatic arthritis disease domains” versus placebo through 16 weeks, with improvements through 52 weeks generally tending to be in refractory domains.
The study, “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,” was presented at ACR 2021.