Dupilumab does not affect correlates of vaccine-induced immunity

A randomized, placebo-controlled trial in adults with moderate-to-severe atopic dermatitis

Andrew Blauvelt, Eric Simpson, Stephen K. Tyring, Lisa A. Purcell, Brad Shumel, Christopher D. Petro, Bolanle Akinlade, Abhijit Gadkari, Laurent Eckert, Neil M.H. Graham, Gianluca Pirozzi, Robert Evans

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: The impact of dupilumab, an anti–interleukin (IL) 4 receptor α antibody that inhibits IL-4 and IL-13 signaling, on vaccine responses of patients with atopic dermatitis (AD) is unknown. Objectives: To assess T-cell–dependent and T-cell–independent humoral immune responses to tetanus and meningococcal vaccines, IgE seroconversion to tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination, and dupilumab efficacy and safety. Methods: In a randomized, double-blinded, placebo-controlled study (NCT02210780), adults with moderate-to-severe AD received dupilumab (300 mg) or placebo weekly for 16 weeks, and single doses of Tdap and quadrivalent meningococcal polysaccharide vaccines at week 12. Primary endpoint was proportion of patients achieving satisfactory IgG response to tetanus toxoid at week 16. Results: In total, 178 patients completed the study. Similar positive immune responses (≥4-fold increase in antibody titer, or an antibody titer of ≥8) were achieved in the dupilumab and placebo groups to tetanus (83.3% and 83.7%, respectively) and meningococcal polysaccharide (86.7% and 87.0%, respectively). Dupilumab significantly decreased total serum IgE; most dupilumab-treated patients were Tdap-IgE seronegative at week 32 (62.2% dupilumab and 34.8% placebo). Dupilumab improved key AD efficacy endpoints (P <.001). Injection-site reactions and conjunctivitis were more common with dupilumab; AD exacerbations more frequent with placebo. Limitation: Patients’ prior vaccination status was not available before enrollment. Conclusion: Dupilumab did not affect responses to the vaccines studied, significantly decreased IgE, and improved measures of AD severity versus placebo, with an acceptable safety profile.

Original languageEnglish (US)
Pages (from-to)158-167.e1
JournalJournal of the American Academy of Dermatology
Volume80
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Atopic Dermatitis
Immunity
Vaccines
Randomized Controlled Trials
Placebos
Immunoglobulin E
Tetanus Toxoid
Meningococcal Vaccines
Antibodies
Vaccination
SAR231893
Interleukin-4 Receptors
Diphtheria Toxoid
Safety
Conjunctivitis
Interleukin-13
Whooping Cough
Tetanus
Humoral Immunity
Interleukin-4

Keywords

  • atopic dermatitis
  • dupilumab
  • IgE
  • meningococcal polysaccharide
  • tetanus toxoid
  • vaccine

ASJC Scopus subject areas

  • Dermatology

Cite this

Dupilumab does not affect correlates of vaccine-induced immunity : A randomized, placebo-controlled trial in adults with moderate-to-severe atopic dermatitis. / Blauvelt, Andrew; Simpson, Eric; Tyring, Stephen K.; Purcell, Lisa A.; Shumel, Brad; Petro, Christopher D.; Akinlade, Bolanle; Gadkari, Abhijit; Eckert, Laurent; Graham, Neil M.H.; Pirozzi, Gianluca; Evans, Robert.

In: Journal of the American Academy of Dermatology, Vol. 80, No. 1, 01.01.2019, p. 158-167.e1.

Research output: Contribution to journalArticle

Blauvelt, A, Simpson, E, Tyring, SK, Purcell, LA, Shumel, B, Petro, CD, Akinlade, B, Gadkari, A, Eckert, L, Graham, NMH, Pirozzi, G & Evans, R 2019, 'Dupilumab does not affect correlates of vaccine-induced immunity: A randomized, placebo-controlled trial in adults with moderate-to-severe atopic dermatitis', Journal of the American Academy of Dermatology, vol. 80, no. 1, pp. 158-167.e1. https://doi.org/10.1016/j.jaad.2018.07.048
Blauvelt, Andrew ; Simpson, Eric ; Tyring, Stephen K. ; Purcell, Lisa A. ; Shumel, Brad ; Petro, Christopher D. ; Akinlade, Bolanle ; Gadkari, Abhijit ; Eckert, Laurent ; Graham, Neil M.H. ; Pirozzi, Gianluca ; Evans, Robert. / Dupilumab does not affect correlates of vaccine-induced immunity : A randomized, placebo-controlled trial in adults with moderate-to-severe atopic dermatitis. In: Journal of the American Academy of Dermatology. 2019 ; Vol. 80, No. 1. pp. 158-167.e1.
@article{3c692a91f58e466eb39e7b2fe65e66ed,
title = "Dupilumab does not affect correlates of vaccine-induced immunity: A randomized, placebo-controlled trial in adults with moderate-to-severe atopic dermatitis",
abstract = "Background: The impact of dupilumab, an anti–interleukin (IL) 4 receptor α antibody that inhibits IL-4 and IL-13 signaling, on vaccine responses of patients with atopic dermatitis (AD) is unknown. Objectives: To assess T-cell–dependent and T-cell–independent humoral immune responses to tetanus and meningococcal vaccines, IgE seroconversion to tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination, and dupilumab efficacy and safety. Methods: In a randomized, double-blinded, placebo-controlled study (NCT02210780), adults with moderate-to-severe AD received dupilumab (300 mg) or placebo weekly for 16 weeks, and single doses of Tdap and quadrivalent meningococcal polysaccharide vaccines at week 12. Primary endpoint was proportion of patients achieving satisfactory IgG response to tetanus toxoid at week 16. Results: In total, 178 patients completed the study. Similar positive immune responses (≥4-fold increase in antibody titer, or an antibody titer of ≥8) were achieved in the dupilumab and placebo groups to tetanus (83.3{\%} and 83.7{\%}, respectively) and meningococcal polysaccharide (86.7{\%} and 87.0{\%}, respectively). Dupilumab significantly decreased total serum IgE; most dupilumab-treated patients were Tdap-IgE seronegative at week 32 (62.2{\%} dupilumab and 34.8{\%} placebo). Dupilumab improved key AD efficacy endpoints (P <.001). Injection-site reactions and conjunctivitis were more common with dupilumab; AD exacerbations more frequent with placebo. Limitation: Patients’ prior vaccination status was not available before enrollment. Conclusion: Dupilumab did not affect responses to the vaccines studied, significantly decreased IgE, and improved measures of AD severity versus placebo, with an acceptable safety profile.",
keywords = "atopic dermatitis, dupilumab, IgE, meningococcal polysaccharide, tetanus toxoid, vaccine",
author = "Andrew Blauvelt and Eric Simpson and Tyring, {Stephen K.} and Purcell, {Lisa A.} and Brad Shumel and Petro, {Christopher D.} and Bolanle Akinlade and Abhijit Gadkari and Laurent Eckert and Graham, {Neil M.H.} and Gianluca Pirozzi and Robert Evans",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.jaad.2018.07.048",
language = "English (US)",
volume = "80",
pages = "158--167.e1",
journal = "Journal of the American Academy of Dermatology",
issn = "0190-9622",
publisher = "Mosby Inc.",
number = "1",

}

TY - JOUR

T1 - Dupilumab does not affect correlates of vaccine-induced immunity

T2 - A randomized, placebo-controlled trial in adults with moderate-to-severe atopic dermatitis

AU - Blauvelt, Andrew

AU - Simpson, Eric

AU - Tyring, Stephen K.

AU - Purcell, Lisa A.

AU - Shumel, Brad

AU - Petro, Christopher D.

AU - Akinlade, Bolanle

AU - Gadkari, Abhijit

AU - Eckert, Laurent

AU - Graham, Neil M.H.

AU - Pirozzi, Gianluca

AU - Evans, Robert

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: The impact of dupilumab, an anti–interleukin (IL) 4 receptor α antibody that inhibits IL-4 and IL-13 signaling, on vaccine responses of patients with atopic dermatitis (AD) is unknown. Objectives: To assess T-cell–dependent and T-cell–independent humoral immune responses to tetanus and meningococcal vaccines, IgE seroconversion to tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination, and dupilumab efficacy and safety. Methods: In a randomized, double-blinded, placebo-controlled study (NCT02210780), adults with moderate-to-severe AD received dupilumab (300 mg) or placebo weekly for 16 weeks, and single doses of Tdap and quadrivalent meningococcal polysaccharide vaccines at week 12. Primary endpoint was proportion of patients achieving satisfactory IgG response to tetanus toxoid at week 16. Results: In total, 178 patients completed the study. Similar positive immune responses (≥4-fold increase in antibody titer, or an antibody titer of ≥8) were achieved in the dupilumab and placebo groups to tetanus (83.3% and 83.7%, respectively) and meningococcal polysaccharide (86.7% and 87.0%, respectively). Dupilumab significantly decreased total serum IgE; most dupilumab-treated patients were Tdap-IgE seronegative at week 32 (62.2% dupilumab and 34.8% placebo). Dupilumab improved key AD efficacy endpoints (P <.001). Injection-site reactions and conjunctivitis were more common with dupilumab; AD exacerbations more frequent with placebo. Limitation: Patients’ prior vaccination status was not available before enrollment. Conclusion: Dupilumab did not affect responses to the vaccines studied, significantly decreased IgE, and improved measures of AD severity versus placebo, with an acceptable safety profile.

AB - Background: The impact of dupilumab, an anti–interleukin (IL) 4 receptor α antibody that inhibits IL-4 and IL-13 signaling, on vaccine responses of patients with atopic dermatitis (AD) is unknown. Objectives: To assess T-cell–dependent and T-cell–independent humoral immune responses to tetanus and meningococcal vaccines, IgE seroconversion to tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccination, and dupilumab efficacy and safety. Methods: In a randomized, double-blinded, placebo-controlled study (NCT02210780), adults with moderate-to-severe AD received dupilumab (300 mg) or placebo weekly for 16 weeks, and single doses of Tdap and quadrivalent meningococcal polysaccharide vaccines at week 12. Primary endpoint was proportion of patients achieving satisfactory IgG response to tetanus toxoid at week 16. Results: In total, 178 patients completed the study. Similar positive immune responses (≥4-fold increase in antibody titer, or an antibody titer of ≥8) were achieved in the dupilumab and placebo groups to tetanus (83.3% and 83.7%, respectively) and meningococcal polysaccharide (86.7% and 87.0%, respectively). Dupilumab significantly decreased total serum IgE; most dupilumab-treated patients were Tdap-IgE seronegative at week 32 (62.2% dupilumab and 34.8% placebo). Dupilumab improved key AD efficacy endpoints (P <.001). Injection-site reactions and conjunctivitis were more common with dupilumab; AD exacerbations more frequent with placebo. Limitation: Patients’ prior vaccination status was not available before enrollment. Conclusion: Dupilumab did not affect responses to the vaccines studied, significantly decreased IgE, and improved measures of AD severity versus placebo, with an acceptable safety profile.

KW - atopic dermatitis

KW - dupilumab

KW - IgE

KW - meningococcal polysaccharide

KW - tetanus toxoid

KW - vaccine

UR - http://www.scopus.com/inward/record.url?scp=85058147382&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058147382&partnerID=8YFLogxK

U2 - 10.1016/j.jaad.2018.07.048

DO - 10.1016/j.jaad.2018.07.048

M3 - Article

VL - 80

SP - 158-167.e1

JO - Journal of the American Academy of Dermatology

JF - Journal of the American Academy of Dermatology

SN - 0190-9622

IS - 1

ER -