Infections in Dupilumab Clinical Trials in Atopic Dermatitis: A Comprehensive Pooled Analysis

Lawrence F. Eichenfield, Thomas Bieber, Lisa A. Beck, Eric L. Simpson, Diamant Thaçi, Marjolein de Bruin-Weller, Mette Deleuran, Jonathan I. Silverberg, Carlos Ferrandiz, Regina Fölster-Holst, Zhen Chen, Neil M.H. Graham, Gianluca Pirozzi, Bolanle Akinlade, George D. Yancopoulos, Marius Ardeleanu

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Background: Patients with moderate-to-severe atopic dermatitis (AD) have increased infection risk, including skin infections and systemic infections. Immunomodulators (e.g., anti-tumor necrosis factors, anti-interleukin [anti-IL]-23, anti-IL-17, Janus kinase inhibitors) increase risk of infections. Dupilumab (a monoclonal antibody blocking the shared receptor component for IL-4 and IL-13) is approved for inadequately controlled moderate-to-severe AD and for moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma. Objective: The aim was to determine the impact of dupilumab on infection rates in patients with moderate-to-severe AD. Methods: This analysis pooled data from seven randomized, placebo-controlled dupilumab trials in adults with moderate-to-severe AD. Exposure-adjusted analyses assessed infection rates. Results: Of 2932 patients, 1091 received placebo, 1095 dupilumab 300 mg weekly, and 746 dupilumab 300 mg every 2 weeks. Treatment groups had similar infection rates overall per 100 patient-years (placebo, 155; dupilumab weekly, 150; dupilumab every 2 weeks, 156; dupilumab combined, 152), and similar non-skin infection rates. Serious/severe infections were reduced with dupilumab (risk ratio 0.43; p < 0.05), as were bacterial and other non-herpetic skin infections (risk ratio 0.44; p < 0.001). Although herpesviral infection rates overall were slightly higher with dupilumab than placebo, clinically important herpesviral infections (eczema herpeticum, herpes zoster) were less common with dupilumab (risk ratio 0.31; p < 0.01). Systemic anti-infective medication use was lower with dupilumab. Conclusions: Dupilumab is associated with reduced risk of serious/severe infections and non-herpetic skin infections and does not increase overall infection rates versus placebo in patients with moderate-to-severe AD. ClinicalTrials.gov Identifiers: NCT01548404, NCT02210780, NCT01859988, NCT02277743, NCT02277769, NCT02260986, and NCT02755649.

Original languageEnglish (US)
Pages (from-to)443-456
Number of pages14
JournalAmerican Journal of Clinical Dermatology
Volume20
Issue number3
DOIs
StatePublished - Jun 1 2019

ASJC Scopus subject areas

  • Dermatology

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    Eichenfield, L. F., Bieber, T., Beck, L. A., Simpson, E. L., Thaçi, D., de Bruin-Weller, M., Deleuran, M., Silverberg, J. I., Ferrandiz, C., Fölster-Holst, R., Chen, Z., Graham, N. M. H., Pirozzi, G., Akinlade, B., Yancopoulos, G. D., & Ardeleanu, M. (2019). Infections in Dupilumab Clinical Trials in Atopic Dermatitis: A Comprehensive Pooled Analysis. American Journal of Clinical Dermatology, 20(3), 443-456. https://doi.org/10.1007/s40257-019-00445-7