Tapinarof Cream for Atopic Dermatitis in Children and Adults: An Updated Meta-Analysis, and Trial Sequential Analysis

<p><strong>Background:</strong> Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by pruritus and eczematous lesions. Conventional topical therapies, including corticosteroids and calcineurin inhibitors, are often associated with adverse effects, highlighting the need for safer long-term alternatives. Tapinarof, a novel aryl hydrocarbon receptor (AhR) modulator, has emerged as a promising nonsteroidal topical agent for AD treatment. This systematic review and meta-analysis aimed to assess the efficacy and safety of tapinarof cream in patients with AD.</p> <p><strong>Methods:</strong> We systematically searched PubMed, Scopus, Embase, Cochrane, and Web of Science from inception to March 2025 to identify studies assessing the efficacy of tapinarof cream in AD. Randomized controlled trials (RCTs) reporting quantitative outcomes were included. Meta-analysis was performed using Review Manager V5.4, calculating relative risks (RRs) and 95% confidence intervals (CIs) for primary and secondary outcomes.</p> <p><strong>Results:</strong> Five studies (six RCTs) involving 1,096 patients treated with tapinarof and 446 with vehicle were analyzed. At 8 weeks, tapinarof 1% cream significantly improved Investigator Global Assessment (IGA) success (RR: 3.21, 95% CI: 2.4–4.28, p < 0.00001) with low heterogeneity (I² = 9%). Similarly, EASI-75 response rates were significantly higher at 8 weeks (RR: 2.86, 95% CI: 2.04–4.02, p < 0.00001). Adverse events, including folliculitis, headache, and nasopharyngitis, were more common with tapinarof, but serious adverse events were not significantly different between groups.</p> <p><strong>Conclusion:</strong> Tapinarof cream demonstrates significant efficacy in achieving IGA treatment success and EASI-75 response with a manageable safety profile. It represents a promising alternative for long-term management of AD, particularly for patients seeking nonsteroidal options</p>