Efficacy and safety of topical Janus kinase and phosphodiesterase inhibitor-4 inhibitors for the treatment of atopic dermatitis: A network meta-analysis

Topical Janus kinase (JAK) and phosphodiesterase-4 (PDE4) inhibitors are novel treatment approaches for atopic dermatitis (AD). This study aimed to compare the efficacy and safety of JAK and PDE4 inhibitors for AD treatment. The databases of PubMed, EMBASE, Web of Science, and Cochrane Library were searched until June 2021 for eligible studies of AD patients treated with topical JAK and PDE4 inhibitors. Baseline and follow-up data were extracted. Efficacy of JAK inhibitors was evaluated using Investigator's Global Assessment (IGA) achieving "clear" or "almost clear", with 2 points or more improvement from baseline at the end of treatment, referred to as "IGA response"). A Bayesian multiple treatment network meta-analysis with fixed effects was performed. Odds ratio (OR) with 95% credibility interval (CrI) were used for comparing the efficacy of JAK and PDE4 inhibitors with placebo for AD. A total of 10 randomized controlled trials of topical JAK and PDE4 inhibitors with 4689 patients were included for analysis. A total of three topical JAK inhibitors and two topical PDE4 inhibitors were included. Compared with placebo, all JAK and PDE4 inhibitors had higher IGA response at 4 weeks of treatment. Notably, with similar safety profile, tofacitinib 2% b.i.d., ruxolitinib 1.5% b.i.d., and delgocitinib 3% b.i.d. showed favorable IGA response compared with topical tacrolimus and corticosteroids. Ranking analysis suggested that among all included JAK and PDE4 inhibitors, tofacitinib 2% b.i.d. had the highest probability of achieving IGA response (SUCRA = 0.880). Besides, JAK and PDE4 inhibitors showed non-inferior safety profile with placebo. This study confirmed that topical JAK and PDE4 inhibitors had promising treatment efficacy and safety for AD patients. Tofacitinib 2% b.i.d., ruxolitinib 1.5% b.i.d. and delgocitinib 3% b.i.d. showed superior efficacy over other JAK and PDE4 inhibitors.