Comparative Efficacy and Safety of Tapinarof 0.5% and 1% Cream Regimens for Atopic Dermatitis: A Network Meta-Analysis

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting quality of life. Tapinarof, a novel aryl hydrocarbon receptor (AhR) modulator, is a promising nonsteroidal treatmentbut, optimal dosing regimens remain unclear. Objectives: This network meta-analysis (NMA) compared the efficacy and safety of tapinarof 0.5%, 1% and 2% creams applied once or twice daily versus placebo in AD. Methods: A systematic search of MEDLINE/PubMed, CENTRAL, Web of Science, ProQuest, and Scopus was conducted from inception to 31 March 2025. Randomized controlled trials (RCTs) evaluating tapinarof versus placebo were included. The frequentist NMA was conducted using STATA 18 software, , with efficacy measured through ≥75% improvement in Eczema Area and Severity Index (EASI-75) and Investigator’s Global Assessment (IGA) response. Surface under the cumulative ranking (SUCRA) probabilities were used to rank treatments. Results: Five RCTs (1,506 patients) were included. Tapinarof 1% twice daily showed the highest efficacy for EASI-75 (odds ratio (OR)=1.89, 95% confidence interval (CI): 1.17–2.62, P<0.001) and IGA response (OR=2.40, 95% CI: 1.30–3.95, P=0.002), ranking as the most effective regimen (SUCRA: 70.3%). Tapinarof 1% once daily and 0.5% twice daily showed moderate efficacy, while tapinarof 0.5% once daily and placebo were the least effective. Heterogeneity was low for EASI-75 (I²=1.4%) but moderate for IGA response (I²=67.14%). Adverse events were generally mild, with folliculitis and contact dermatitis being the most reported. Conclusions: Tapinarof 1% twice daily is the most effective and well-tolerated regimen for AD, providing critical insights for clinical decision-making, although further head-to-head trials are needed.