Topical brepocitinib, a small-molecule Janus kinase 1 (JAK1) and tyrosine kinase 2 (TYK2) inhibitor, effectively and safely treated mild to moderate atopic dermatitis (AD) in adults, according to data from a phase 2b, multicenter, double-blind, dose-ranging study published in the British Journal of Dermatology.
Investigators randomly assigned adult patients with mild to moderate AD diagnosed 3 or more months prior 1:1 to receive 1 of 8 treatments for 6 weeks: brepocitinib 0.1% once daily, 0.3% once or twice daily, 1.0% once or twice daily, 3.0% once daily, or vehicle once or twice daily. The primary endpoint was the percent change from baseline in Eczema Area Severity Index (EASI) score at week 6. The key secondary endpoint was the percentage of patients who achieved an Investigator’s Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and a 2-point or greater reduction in IGA from baseline by week 6. Investigators used analysis of covariance (ANCOVA) to assess change in EASI score from baseline.
There were 292 patients included in the trial. The mean age was 40.2 years and 53.4% were women. The mean EASI score was 7.3 at baseline and about half of participants had an IGA score of 2 or 3 (mild or moderate).
Overall, 240 patients completed treatment. EASI scores for patients treated with brepocitinib 1% once and twice daily improved significantly from baseline at week 6 (least squares [LS] mean: once daily: -70.1, 90% CI, -82.1 to -58.0; twice daily: -75.0, 90% CI, -83.8 to -66.2) compared with vehicle (LS mean: once daily: -44.4, 90% CI, -57.3 to -31.6; twice daily: -47.6, 90% CI, -57.5 to -37.7). All other brepocitinib groups had EASI baseline reductions that were numerically greater than vehicle but not statistically significant.
In 5 of 6 active treatment groups, the percentage of patients with an IGA score of 0 or 1 as well as a 2-point reduction in IGA score was significantly higher compared with the respective vehicle group. Patients treated with brepocitinib 1% twice daily had numerically greater IGA scores and 2-point reductions but reductions were not statistically significant compared to its vehicle group.
Overall, 37.0% of patients experienced treatment emergent adverse events (TEAEs), with the highest percentage of TEAEs and study discontinuations due to TEAEs reported in the vehicle groups. The most common TEAEs leading to discontinuation were related to worsening AD symptoms. There was no dose-dependent trend for adverse event frequency, and no serious adverse events or deaths occurred. The most common TEAEs were nasopharyngitis and worsening AD. No clinically meaningful trends were seen in laboratory results of patient blood samples.
The study was limited by small group sizes and a short treatment duration.
“This topical cream formulation of brepocitinib offers an alternative to petrolatum-based ointments,” the study authors noted.
Disclosure: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Landis MN, Arya M, Smith S, et al. Efficacy and safety of topical brepocitinib for the treatment of mild-to-moderate atopic dermatitis: a phase IIb, randomized, double-blind, vehicle-controlled, dose-ranging and parallel-group study. Br J Dermatol. Published online August 10, 2022. doi:10.1111/bjd.21826