Abstract
BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin condition with a significant disease burden. Systemic therapies, including Janus kinase inhibitors, offer targeted treatment options for moderate-to-severe AD. Upadacitinib (UPA) is a selective Janus kinase 1 inhibitor which has demonstrated promising efficacy in clinical trials. This systematic review and meta-analysis evaluate the efficacy and safety of UPA in AD treatment. METHODS: A comprehensive systematic search was conducted across the following databases: PubMed, Web of Science, and Google Scholar, following PRISMA guidelines. Randomized controlled trials evaluating UPA for moderate to severe AD were included. Efficacy outcomes included Eczema Area and Severity Index (EASI) improvement (EASI-75, EASI-90), pruritus reduction, and overall treatment response. Safety outcomes assessed the adverse events and tolerability. A meta-analysis was performed using a random-effects model to estimate pooled RRs and confidence intervals (CIs). RESULTS: Five randomized controlled trials met the inclusion criteria with a total of 2208 participants (1153 in the treatment group and 1055 in the control group). UPA significantly improved EASI-75 response rates compared to placebo or dupilumab (pooled RR = 1.77, 95% CI: 1.34-2.33; P < .0001), and showed a superior EASI-90 response (pooled RR = 3.83, 95% CI: 2.17-6.78; P < .0001). Pruritus numeric rating scale scores improved significantly (RR = 1.98, 95% CI: 1.42-2.76; P < .0001). Subgroup analysis revealed that both UPA 15 mg and 30 mg were superior to placebo or dupilumab, with EASI-75 subgroup RRs of 2.64 (95% CI: 0.84-8.34) and 1.95 (95% CI: 1.09-3.51), respectively. Similarly, EASI-90 responses were markedly higher with 15 mg (RR = 8.70, 95% CI: 3.60-21.02) and 30 mg (RR = 6.01, 95% CI: 0.90-40.03), with greater effect observed at the higher dose. CONCLUSION: UPA is an effective systemic treatment for moderate-to-severe AD, demonstrating rapid and sustained symptomatic improvement with an acceptable safety profile. While its efficacy exceeds the current biological therapies in some aspects, long-term safety monitoring and comparative trials are needed to optimize treatment strategies.