TY - JOUR
T1 - Infections in Dupilumab Clinical Trials in Atopic Dermatitis
T2 - A Comprehensive Pooled Analysis
AU - Eichenfield, Lawrence F
AU - Bieber, Thomas
AU - Beck, Lisa A
AU - Simpson, Eric L
AU - Thaçi, Diamant
AU - de Bruin-Weller, Marjolein
AU - Deleuran, Mette
AU - Silverberg, Jonathan I
AU - Ferrandiz, Carlos
AU - Fölster-Holst, Regina
AU - Chen, Zhen
AU - Graham, Neil M H
AU - Pirozzi, Gianluca
AU - Akinlade, Bolanle
AU - Yancopoulos, George D
AU - Ardeleanu, Marius
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/6
Y1 - 2019/6
N2 - 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.
AB - 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.
KW - Adult
KW - Antibodies, Monoclonal, Humanized
KW - Antibodies, Monoclonal/administration & dosage
KW - Clinical Trials, Phase II as Topic
KW - Clinical Trials, Phase III as Topic
KW - Dermatitis, Atopic/complications
KW - Double-Blind Method
KW - Humans
KW - Incidence
KW - Injections, Subcutaneous
KW - Placebos/administration & dosage
KW - Randomized Controlled Trials as Topic
KW - Severity of Illness Index
KW - Skin Diseases, Infectious/epidemiology
KW - Treatment Outcome
UR - http://www.scopus.com/inward/record.url?scp=85065521765&partnerID=8YFLogxK
U2 - 10.1007/s40257-019-00445-7
DO - 10.1007/s40257-019-00445-7
M3 - Article
C2 - 31066001
SN - 1175-0561
VL - 20
SP - 443
EP - 456
JO - American Journal of Clinical Dermatology
JF - American Journal of Clinical Dermatology
IS - 3
ER -