Br J Dermatol. 2023 Mar 27:ljad098. doi: 10.1093/bjd/ljad098. Online ahead of print.
ABSTRACT
BACKGROUND: Plaque psoriasis (PsO) is an inflammatory skin disease driven, in part, by the activation of Janus kinase (JAK) signalling pathways.
OBJECTIVE: To assess the efficacy and safety of multiple doses of topical brepocitinib, a tyrosine kinase 2/JAK1 inhibitor, in participants with mild-to-moderate PsO.
METHOD: This phase IIb, multicentre, randomised, double-blind study was conducted in two stages. In stage one, participants received one of eight treatments for 12 weeks: brepocitinib 0·1% once daily (QD), 0·3% QD or twice daily (BID), 1·0% QD or BID, 3·0% QD, or vehicle QD or BID. In stage two, participants received brepocitinib 3·0% BID or vehicle BID. The primary endpoint was the change from baseline in Psoriasis Area and Severity Index (PASI) score at week 12, analysed using analysis of covariance. The key secondary endpoint was the proportion of participants who achieved a Physician Global Assessment (PGA) response (score of clear (0) or almost clear (1) and an improvement of ≥2 points from baseline) at week 12. Additional secondary endpoints included the difference vs. vehicle in change from baseline in PASI, using mixed-model repeated measures (MMRM), and the change from baseline in Peak Pruritus Numerical Rating Scale (PP-NRS) at week 12. Safety was monitored.
RESULTS: Overall, 344 participants were randomised. Topical brepocitinib did not result in statistically significant changes from respective vehicle controls in the primary or key secondary efficacy endpoints for any dose group. At week 12, least squares mean (LSM) change from baseline in PASI score ranged from -1·4 to -2·4 for brepocitinib QD groups vs. -1·6 for vehicle QD, and from -2·5 to -3·0 for brepocitinib BID groups vs. -2·2 for vehicle BID. From week 8, change from baseline in PASI score separated from vehicle in all brepocitinib BID groups. Brepocitinib was well-tolerated with AEs occurring at similar rates across groups. One participant in the brepocitinib 1·0% QD group developed a treatment-related AE of herpes zoster in the neck area.
CONCLUSION: Topical brepocitinib was well-tolerated but did not result in statistically significant changes vs. vehicle when administered at the doses evaluated to treat signs and symptoms of mild-to-moderate PsO.
CLINICALTRIALS.GOV IDENTIFIER: NCT03850483.
PMID:36972293 | DOI:10.1093/bjd/ljad098
