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

• Published in: Journal of the American Academy of Dermatology Vol. 78; no. 1; pp. 62 - 69.e1
• Main Authors: Fleming, Patrick, Drucker, Aaron M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2018
• Subjects: Adult; Antibodies, Monoclonal - therapeutic use; atopic dermatitis; atopic eczema; Dermatitis, Atopic - diagnosis; Dermatitis, Atopic - drug therapy; Dermatitis, Atopic - epidemiology; Dose-Response Relationship, Drug; Drug Administration Schedule; dupilumab; Female; herpes infections; Humans; Incidence; infections; Injections, Subcutaneous; Male; meta-analysis; Prognosis; Randomized Controlled Trials as Topic; Risk Assessment; Skin Diseases, Infectious - epidemiology; Skin Diseases, Infectious - microbiology; Skin Diseases, Infectious - prevention & control; Treatment Outcome; RR; RCT; IL; OR; CI; infections; meta-analysis; atopic dermatitis; HSV; atopic eczema; herpes infections; dupilumab
• ISSN: 0190-9622; 1097-6787
• DOI: 10.1016/j.jaad.2017.09.052

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. We aimed to determine the impact of dupilumab on rates of skin and other infections in patients with moderate-to-severe AD. 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. 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). 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. 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.