Comparative efficacy of targeted systemic therapies for moderate-to-severe atopic dermatitis: a network meta-analysis of phase 3–4 randomized trials

BACKGROUND: The emergence of systemic targeted therapies for atopic dermatitis (AD) has significantly transformed the treatment landscape. OBJECTIVE: This network meta-analysis aims to systematically evaluate the relative efficacy of approved systemic targeted therapies in adult patients with moderate-to-severe AD. METHODS: Phase 3 or 4 randomized controlled trials (RCTs) assessing approved systemic targeted therapies for moderate-to-severe AD published up to July 29, 2025, were systematically identified. A Bayesian network meta-analysis was performed to analyze the proportion of patients achieving key efficacy indicators, including EASI-75, EASI-90, IGA 0/1, and NRS response. RESULTS: A total of 27 reports encompassing 33 trials and 16,334 participants were included. The network meta-analysis demonstrated that Upadacitinib 30 mg consistently exhibited the highest probability of achieving each clinical endpoint. While pairwise comparisons revealed statistically significant differences among multiple targeted therapies, no significant differences were observed between dupilumab 300 mg and stapokibart 300 mg, or between ivarmacitinib 8 mg and upadacitinib 15 mg. CONCLUSION: Among currently approved targeted systemic therapies, upadacitinib 30 mg once daily ranked highest across all evaluated efficacy outcomes. However, these findings are derived primarily from indirect comparisons, and head-to-head randomized trials are needed to confirm the relative effectiveness of these therapies.