Immune response evolution in peanut epicutaneous immunotherapy for peanut-allergic children

Authors

Marie Bastin, DNAlytics, Ottignies-Louvain-la-Neuve, Belgium.
Warner W. Carr, Allergy and Asthma Associates of Southern California, Southern California Research, California, Mission Viejo, USA.
Carla M. Davis, Department of Pediatrics, Immunology, Allergy, and Retrovirology Division, Baylor College of Medicine, Houston, Texas, USA.
David M. Fleischer, Children's Hospital Colorado, University of Colorado Denver School of Medicine, Aurora, Colorado, USA.
Jay A. Lieberman, The University of Tennessee Health Science Center, Le Bonheur Children's Hospital, Memphis, Tennessee, USA.
S Shahzad Mustafa, Rochester Regional HealthFollow
Thibault Helleputte, DNAlytics, Ottignies-Louvain-la-Neuve, Belgium.
Timothée Bois, DBV Technologies SA, Montrouge, France.
Dianne E. Campbell, DBV Technologies SA, Montrouge, France.
Todd D. Green, DBV Technologies SA, Montrouge, France.
Matthew Greenhawt, Children's Hospital Colorado, University of Colorado Denver School of Medicine, Aurora, Colorado, USA.

Department

Allergy and Immunology

Document Type

Article

Publication Title

Allergy

Abstract

Background: Epicutaneous immunotherapy with investigational Viaskin™ Peanut 250 μg (DBV712) has demonstrated statistically superior desensitization versus placebo in peanut-allergic children in clinical trials. It is unclear whether serologic biomarkers predict response.

Methods: Serum-specific IgG4 and IgE (whole peanut and components) from subjects enrolled in the phase 3 Efficacy and Safety of Viaskin Peanut in Children With IgE-Mediated Peanut Allergy study were examined by exploratory univariate and multivariate analyses to determine trajectories and predictors of treatment response, based upon peanut protein eliciting dose (ED) at Month (M) 12 double-blind placebo-controlled food challenge.

Results: Among Viaskin Peanut-treated subjects, peanut sIgG4 significantly increased from baseline through M12 and peanut sIgE peaked at M3 and fell below baseline by M12, with sIgG4 and sIgE peanut components mirroring these trajectories. Placebo subjects had no significant changes. By univariate analysis, M12 peanut sIgG4/sIgE was higher in treatment responders (p < 0.001) and had highest area under the curve (AUC) for predicting ED ≥ 300 mg and ≥ 1000 mg (AUC 69.5% and 69.9%, respectively). M12 peanut sIgG4/sIgE > 20.1 predicted M12 ED ≥300 mg (80% positive predictive value). The best performing component was Ara h 1 sIgE < 15.7 kUA /L (AUC 66.5%). A multivariate model combining Ara h 1 and peanut sIgG4/sIgE had an AUC of 68.2% (ED ≥ 300 mg) and 67.8% (ED ≥ 1000 mg).

Conclusions: Peanut sIgG4 rise most clearly differentiated Viaskin Peanut versus placebo subjects. sIgG4/sIgE ratios > 20.1 and the combination of Ara h 1 and peanut sIgG4/sIgE had moderate ability to predict treatment response and could potentially be useful for clinical monitoring. Additional data are needed to confirm these relationships.

First Page

2467

Last Page

2476

DOI

10.1111/all.15709

Volume

78

Issue

9

Publication Date

9-1-2023

PubMed ID

36916639

Recommended Citation

Bastin, M., Carr, W. W., Davis, C. M., Fleischer, D. M., Lieberman, J. A., Mustafa, S. S., Helleputte, T., Bois, T., Campbell, D. E., Green, T. D., & Greenhawt, M. (2023). Immune response evolution in peanut epicutaneous immunotherapy for peanut-allergic children. Allergy, 78 (9), 2467-2476. https://doi.org/10.1111/all.15709