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

Am J Clin Dermatol. 2019 Jun;20(3):443-456. doi: 10.1007/s40257-019-00445-7.


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.

MeSH terms

  • Adult
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Dermatitis, Atopic / complications
  • Dermatitis, Atopic / diagnosis
  • Dermatitis, Atopic / drug therapy*
  • Double-Blind Method
  • Humans
  • Incidence
  • Injections, Subcutaneous
  • Placebos / administration & dosage
  • Placebos / adverse effects
  • Randomized Controlled Trials as Topic
  • Severity of Illness Index
  • Skin Diseases, Infectious / epidemiology*
  • Skin Diseases, Infectious / etiology
  • Skin Diseases, Infectious / prevention & control
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Placebos
  • dupilumab