Comparative Efficacy of Novel Non-steroidal Topical Therapies for Atopic Dermatitis: A Systematic Review and Network Meta-analysis

Despite the availability of several non-steroidal topical therapies for atopic dermatitis (AD), their comparative speed of clinical response remains unclear. This meta-analysis compared the efficacy of novel non-steroidal topical therapies for AD. Four databases were searched for randomized controlled trials (RCTs) evaluating topical difamilast 1% twice daily (BID), tapinarof 1% once daily (QD), ruxolitinib 1.5% BID, roflumilast 0.05% or 0.15% QD in patients with AD. Outcomes included Investigator’s Global Assessment Treatment Success (IGA-TS) and 50%, 75% and 90% improvement in Eczema Area and Severity Index (EASI-50, EASI-75 and EASI-90) at weeks 1, 2, 4 and 8. Frequentist random-effects network meta-analyses estimated odds ratios (ORs) and 95% confidence intervals (CIs), primarily comprising indirect comparisons between non-steroidal topicals using a common vehicle comparator. Twenty-two RCTs (5843 participants) were included. Ruxolitinib demonstrated the highest odds of IGA-TS versus vehicle at week 2 (OR 8.94; 95% CI 5.28–15.12), 4 (OR 9.03; 95% CI 6.27–13.01) and 8 (OR 9.03; 95% CI 6.52–12.50), along with EASI-75 and EASI-90. Difamilast demonstrated favourable EASI-75 (OR 5.34; 95% CI 3.51–8.12) and EASI-90 (OR 6.71; 95% CI 3.79–11.89) responses versus vehicle at week 4; later data were unavailable. Efficacy profiles varied across novel non-steroidal topical therapies, with ruxolitinib demonstrating the strongest and most consistent relative efficacy estimates. Response magnitude and timing remain important considerations when selecting topical AD treatments.