Efficacy and Safety of TRPV1 Antagonists for Atopic Dermatitis: A Systematic Review and Meta-Analysis Focusing on Asivatrep.

The transient receptor potential vanilloid 1 (TRPV1) channel is a critical mediator in pruritus signaling, and its antagonists represent a promising therapeutic strategy to disrupt the "itch-scratch" cycle in atopic dermatitis (AD). This meta-analysis was conducted to evaluate the efficacy and safety of TRPV1 antagonists for AD, with available evidence focusing on the topical agent asivatrep. A systematic search was performed across seven databases (e.g., CENTRAL, Embase, and MEDLINE) from inception to December 27, 2025, without language restrictions. With study selection, data extraction, and risk-of-bias assessment completed independently by two investigators, a random-effects model was applied for meta-analysis. Although our search strategy was designed to capture all TRPV1 antagonists, only two randomized controlled trials (RCTs, n = 431) met the inclusion criteria, both evaluating the topical, highly selective TRPV1 antagonist asivatrep (PAC-14028) 1.0% cream. Compared with the vehicle control, asivatrep significantly improved physician-assessed skin lesions (e.g., Investigator's Global Assessment 0/1 response: risk ratio [RR] 3.23, 95% confidence interval [CI] 2.02 to 5.17; Eczema Area and Severity Index (EASI)-75 response: RR 1.84, 95% CI 1.18 to 2.87) and significantly alleviated patient-reported pruritus and sleep disturbance. The incidence of all adverse events (RR 1.41, 95% CI 0.53 to 3.76) and drug-related adverse events (RR 0.64, 95% CI 0.08 to 4.97) in the Asivatrep 1.0% group did not differ significantly from the vehicle group. In conclusion, topical asivatrep (1.0% cream) effectively and safely improves lesion severity and pruritus in patients with mild-to-moderate AD. However, as current evidence is confined to asivatrep in mild-to-moderate AD, a class effect for TRPV1 antagonists cannot be established.