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

*Korrespondierende/r Autor/-in für diese Arbeit
33 Zitate (Scopus)

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.

OriginalspracheEnglisch
ZeitschriftAmerican Journal of Clinical Dermatology
Jahrgang20
Ausgabenummer3
Seiten (von - bis)443-456
Seitenumfang14
ISSN1175-0561
DOIs
PublikationsstatusVeröffentlicht - 01.06.2019

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)

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