Risk of infection in patients with atopic dermatitis treated with dupilumab: A meta-analysis of randomized controlled trials

Background: Atopic dermatitis (AD) is characterized by skin barrier defects, T helper type 2 cell activation, and increased risk for cutaneous and extracutaneous infections. In clinical trials, dupilumab appeared to decrease rates of skin infections in AD. Objective: We aimed to determine the impact of dupilumab on rates of skin and other infections in patients with moderate-to-severe AD. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials of dupilumab for AD. We searched the PubMed database for relevant studies. Risk ratios (RRs) and 95% confidence intervals (CIs) for skin infections, herpesvirus infections, and overall infections and infestations were calculated for dupilumab compared with for placebo by using binary random effects meta-analysis. For the analysis of eczema herpeticum, Peto odds ratios were calculated. Results: Eight randomized controlled trials in 4 publications with 2706 participants were included, with follow-up time ranging from 4 to 52 weeks. Meta-analysis including all dosing schedules and follow-up times showed a RR of skin infection of 0.54 (95% CI, 0.42-0.70) and an odds ratio of eczema herpeticum of 0.34 (95% CI, 0.14-0.84) for dupilumab compared with placebo. No significant association was found for dupilumab with overall herpesvirus infections (RR, 1.16; 95% CI, 0.78-1.74) and overall infections (RR, 0.98; 95% CI, 0.83-1.16). Limitations: Our analysis is limited by the short follow-up time in most trials and the relatively low number of patients treated with dupilumab to date. Conclusions: Dupilumab is associated with a decreased incidence of skin infections and eczema herpeticum in adults with moderate-to-severe AD. The mechanism underlying this association is uncertain but is likely related to improvement in AD severity. Dupilumab, a monoclonal antibody targeting interleukin 4 and interleukin 13, appears to significantly decrease the risk for skin infections and eczema herpeticum in adults with moderate-to-severe AD.