Dupilumab has a profound effect on <scp>specific‐IgE</scp> levels of several food allergens in atopic dermatitis patients

Abstract

Dupilumab is the first biological developed for atopic dermatitis (AD). It blocks the signaling pathway of Type 2 (T2)-related cytokines, IL-4 and IL-13, and might therefore also has an effect on other T2-related diseases, such as food allergy (FA).1 AD has been shown to be a major risk factor for food sensitization and the development of immunoglobulin E (IgE)-mediated food allergy.2, 3 Dupilumab treatment in AD patients reduces total serum IgE; however, the course of specific IgE (sIgE) levels for food allergens during dupilumab treatment has not been defined yet.1 Therefore, the aim of this study was to investigate the effect of dupilumab on sIgE levels in patients with moderate-to-severe AD with comorbid food allergy. Adult AD patients treated with dupilumab with a suggestive clinical history of food allergy (resp. peanut, hazelnut, almond, cashew nut, walnut, kiwi, and apple), and a corresponding positive sIgE (≥0.35 kU/L) at the start of treatment, were included. Data were extracted from the prospectively BioDay registry between October 2017 and February 2022. All patients provided written informed consent. Linear mixed models were used to model the development of sIgE values over time, providing median IgE values (with 95% CIs) and corresponding percentage decline. All analyses were performed for each food separately (detailed explanation of methods is described in the Supporting Information). A total of 125 AD patients reporting 307 food allergies were included, with 2682 corresponding sIgE samples. Most patients were allergic to one (n = 42, 33.6%) or two foods (n = 35, 28.0%) (Table 1). Peanut and hazelnut (51.2% and 52.0%) were the most common causative foods. An estimated sustained percentage decrease of sIgE levels was observed for all food allergens during dupilumab treatment, with a decrease ranging from 53.0% (95% CI: 46.3–59.7) for peanut extract to 62.9% (95% CI: 57.0–68.8) for apple after 1 year, and from 80.5% (95% CI: 68.9–92.1) for walnut to 86.9% (95% CI: 78.7–95.2) for kiwi after 3 years of treatment (Figure 1). After 3 years, the lowest median sIgE levels were observed for almond (0.4, 95% CI: 0.2–0.6), while hazelnut had the highest median sIgE levels (3.0, 95% CI: 2.1–4.3) (Figure S1). This is the first study that showed a profound decrease in sIgE levels of food allergens during dupilumab treatment (up to 3.5 years) in a large population of food-allergic AD patients. At present, there is no direct evidence that a decrease of sIgE levels leads to less clinical reactivity; however, several studies indirectly support that the decrease of sIgE levels could be a surrogate marker for the decrease of food-allergic reactions.4, 5 Furthermore, the case report of Rial et al.,6 showed a decrease of food-allergic reaction to corn and nuts after accidental food ingestion during dupilumab treatment for AD, and provides clinical evidence for the positive effect of dupilumab in decreasing the severity of a food-allergic reaction. In our study, 33 of 40 patients, who accidentally ingested foods during dupilmab treatment, reported a decrease in severity of food-allergic symptoms (Table S2). However, studies including food challenges before and during dupilumab treatment are necessary to evaluate and objectify whether dupilumab is an effective treatment for FA. We hypothesize that dupilumab might decrease the severity of food-allergic reactions due to inhibiting the IL-4/IL-13-pathway. IL-4 and IL-13 play a key role in differentiation of plasma cells from B lymphocytes, IgE class-switching and subsequently expansion, maintenance and activation of mast cells and basophils, causing the release of mediators leading to allergic symptoms.1 Therefore, blocking the IL-4/IL-13 signaling pathway, by using dupilumab, might diminish food-allergic reactions by interfering in the food-allergic reaction cascade. In conclusion, this daily practice study shows that dupilumab treatment induces a sustained decrease in sIgE levels, showing an estimated decrease of at least 80% for all foods after 3 years of treatment. These findings endorse a possible additional advantage of dupilumab for AD patients with concomitant food allergy. We thank all the patients for their participation in the study. Patients included in this manuscript participated in the BioDay registry sponsored by Sanofi Genzyme. L. Spekhorst is a speaker for Abbvie. L. van der Rijst, N. Zuithoff, A. Knulst, and M. van Megen have nothing to disclose. M. de Graaf is an advisor, consultant, speaker or investigator for Sanofi-Genzyme, Regeneron Pharmaceuticals, LEO Pharma and Eli Lilly. M. De Bruin-Weller has been a consultant, advisory board member, and/or speaker for AbbVie, Almirall, Arena, Aslan, Eli Lilly, Galderma, Janssen, Leo Pharma, Pfizer, Regeneron, and Sanofi-Genzyme. TM. Le has been an advisory board member for Novartis and speaker for Thermo Fisher Scientific. Appendix S1 Figure S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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