Attenuating the atopic march: Meta-analysis of the dupilumab atopic dermatitis database for incident allergic events.

Atopic march IgE responsiveness, atopic antibodies, monoclonal asthma dermatitis, atopic dupilumab eczema food hypersensitivity meta-analysis rhinitis, allergic

Journal

The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002

Informations de publication

Date de publication:
03 2023
Historique:
received: 21 12 2021
revised: 29 06 2022
accepted: 02 08 2022
pubmed: 10 9 2022
medline: 8 3 2023
entrez: 9 9 2022
Statut: ppublish

Résumé

Atopic march refers to the sequential development of allergic diseases from infancy through adolescence, typically beginning with atopic dermatitis (AD), followed by food allergy and then airway diseases, later evolving to broader or worsened spectrum of allergic diatheses. No intervention has shown to alter its course. We sought to determine the rate of acquisition of new or worsened allergic events for dupilumab versus placebo in patients with AD. Allergy-associated events from 12 clinical trials were grouped into 17 allergy categories, and IgE changes from baseline were defined. A new/worsened event was considered one step of atopic march. Treatment effect was assessed by incidence rate ratios (IRRs), dupilumab versus placebo, by meta-analysis. The duration of pooled AD studies was 4 to 52 weeks (1359 patient-years; n = 2296 dupilumab, n = 1229 placebo, median age 35 years). The median age at AD onset was 2 years. Baseline allergic disease burden was comparable between groups. Dupilumab reduced the risk of new/worsening allergies by 34% (IRR 0.66; 95% confidence interval [CI], 0.52-0.84) and new allergies by 37% (IRR 0.63; 95% CI, 0.48-0.83) versus placebo. Including IgE category shift, the IRR for combined new/worsening allergies was reduced by 54% (IRR 0.46; 95% CI, 0.36-0.57). These treatment benefits did not reverse on treatment discontinuation in off-treatment follow-up. The acquisition/worsening of allergic conditions suggestive of atopic march was observed in a pooled adult/adolescent AD study population with inadequately controlled AD. Treatment with dupilumab reduced new/worsened allergy events versus placebo; inclusion of IgE category change increased the apparent benefit.

Sections du résumé

BACKGROUND
Atopic march refers to the sequential development of allergic diseases from infancy through adolescence, typically beginning with atopic dermatitis (AD), followed by food allergy and then airway diseases, later evolving to broader or worsened spectrum of allergic diatheses. No intervention has shown to alter its course.
OBJECTIVE
We sought to determine the rate of acquisition of new or worsened allergic events for dupilumab versus placebo in patients with AD.
METHODS
Allergy-associated events from 12 clinical trials were grouped into 17 allergy categories, and IgE changes from baseline were defined. A new/worsened event was considered one step of atopic march. Treatment effect was assessed by incidence rate ratios (IRRs), dupilumab versus placebo, by meta-analysis.
RESULTS
The duration of pooled AD studies was 4 to 52 weeks (1359 patient-years; n = 2296 dupilumab, n = 1229 placebo, median age 35 years). The median age at AD onset was 2 years. Baseline allergic disease burden was comparable between groups. Dupilumab reduced the risk of new/worsening allergies by 34% (IRR 0.66; 95% confidence interval [CI], 0.52-0.84) and new allergies by 37% (IRR 0.63; 95% CI, 0.48-0.83) versus placebo. Including IgE category shift, the IRR for combined new/worsening allergies was reduced by 54% (IRR 0.46; 95% CI, 0.36-0.57). These treatment benefits did not reverse on treatment discontinuation in off-treatment follow-up.
CONCLUSIONS
The acquisition/worsening of allergic conditions suggestive of atopic march was observed in a pooled adult/adolescent AD study population with inadequately controlled AD. Treatment with dupilumab reduced new/worsened allergy events versus placebo; inclusion of IgE category change increased the apparent benefit.

Identifiants

pubmed: 36084766
pii: S0091-6749(22)01176-9
doi: 10.1016/j.jaci.2022.08.026
pii:
doi:

Substances chimiques

dupilumab 420K487FSG
Antibodies, Monoclonal, Humanized 0
Immunoglobulin E 37341-29-0

Types de publication

Meta-Analysis Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

756-766

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Gregory P Geba (GP)

Regeneron Pharmaceuticals, Inc, Tarrytown, NY. Electronic address: gregory.geba@regeneron.com.

Dateng Li (D)

Regeneron Pharmaceuticals, Inc, Tarrytown, NY.

Meng Xu (M)

Regeneron Pharmaceuticals, Inc, Tarrytown, NY.

Kusha Mohammadi (K)

Regeneron Pharmaceuticals, Inc, Tarrytown, NY.

Richa Attre (R)

Regeneron Pharmaceuticals, Inc, Tarrytown, NY.

Marius Ardeleanu (M)

Regeneron Pharmaceuticals, Inc, Tarrytown, NY.

Bret Musser (B)

Regeneron Pharmaceuticals, Inc, Tarrytown, NY.

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Classifications MeSH