The safety of systemic Janus kinase inhibitors in atopic dermatitis: a systematic review and network meta-analysis.

Abstract

Janus kinase (JAK) inhibitors have been developed to treat moderate to severe atopic dermatitis, but there is little evidence comparing the safety profile of these drugs. The aim of this study is to compare the relative safety of the different systemic JAK inhibitors in atopic dermatitis. Medline, EMBASE, and clinicaltrials.gov were searched to identify phase 2/3, clinical trials (RCTs) designed to evaluate the efficacy and safety of systemic JAK inhibitors in atopic dermatitis. Outcomes were the risk of any adverse event (AE), serious AEs, AEs leading to treatment discontinuation, any infection, serious infections, herpes zoster infection, and any cardiac or vascular event. Eighteen RCTs were included. Compared with placebo, baricitinib (odds ratio [OR] 1.25, 95% credible interval [CrI] 1.03-1.55), abrocitinib (OR 1.54, 95% CrI 1.25-1.90), and upadacitinib (OR 1.46, 95% CrI 1.19-1.81) increase the risk of any adverse event. Abrocitinib (OR 1.62, 95% CrI 1.7-2.72), upadacitinib (OR 1.67, 95% CrI 1.19-2.43), and dupilumab (OR 1.69, 95% CrI 1.02-2.79) increase the risk of infections when compared with placebo. Dupilumab has a reduced risk of herpes zoster infection when compared with upadacitinib (OR 0.23; 95% CrI 0.08-0.81) No further statistically significant risk differences between treatments were identified. The results suggest systemic JAK inhibitors for atopic dermatitis have a similar safety profile. However, as current data present limitations, postmarketing safety evidence will be crucial to draw definitive conclusions regarding the safety of JAK inhibitors.