Managing Food Allergies with Dupilumab in Pediatric Dermatology

Image Credit: © Марина Терехова - stock.adobe.com

A recent study focused on evaluating the impact of dupilumab, a monoclonal antibody that inhibits interleukin (IL)-4 and IL-13 signaling pathways, on food-specific immunoglobulin E (IgE) levels in pediatric patients with moderate to severe atopic dermatitis (AD) and concurrent food allergies (FA).¹ Researchers stated that AD and FA “significantly” affect quality of life and can have substantial socio-economic implications.² AD has been closely linked to IgE-mediated FA, where allergen-specific T helper type 2 cells trigger pro-inflammatory cytokine release (e.g., IL-4, IL-13), leading to B cell production of specific IgE (sIgE).³

Dupilumab, approved for treating moderate to severe AD from 6 months of age, has shown efficacy in reducing sIgE levels to various food allergens in adults with AD and FA.⁴ However, its effect on pediatric patients, who often develop FA early in life, remains unclear. Therefore, the study aimed to investigate dupilumab's impact on sIgE levels for 10 common food allergens (peanut, hazelnut, cashew nut, pistachio, almond, walnut, hen's egg, cow's milk, kiwi, apple) in children aged 4 to 17 years with moderate to severe AD.

Data from the BioDay registry (August 2019 - July 2023) were analyzed using a covariance pattern model to track changes in sIgE levels over a 1-year follow-up period. Patients included had a clinical history suggestive of FA and positive sIgE (≥0.35 kU/L) to the specified foods at baseline. The study also included patients who had avoided certain foods due to severe reactions to related allergens or parental anxiety.

Methods

In total, 36 pediatric patients with a mean age of 12.5 (standard deviation ±3.6) years were included in the study. Researchers stated a total of 120 FAs, with 1008 corresponding sIgE samples, were identified. Peanut (18.3%) and hazelnut (16.7%) were the most common foods to which patients were sensitized. The study noted that 2 (5.6%) patients discontinued dupilumab treatment at a mean treatment duration of 16.5 weeks.

During year 1 of treatment, researchers observed a “significant” percentage decrease for all food allergens, with the most profound decrease in the first 16 weeks of treatment. In all food allergens (sIgE extracts and components), the study reported a decrease ranging from 70.5% (95% CI: 37.1–86.1, for apple) to 82.5% (95% CI: 75.0–87.7, for cashew nut). Higher baseline sIgE levels were not reported to correspond to faster or slower decrease than lower baseline sIgE levels. In addition, researchers saw no significant differences in the percentage decrease in sIgE levels between patients sensitized to 1 food and those sensitized to multiple foods.

Results

The study demonstrated a significant reduction in sIgE levels to 10 common food allergens in pediatric patients with moderate to severe AD treated with dupilumab. After 1 year of treatment, sIgE levels decreased by 70.5% to 82.5%. This reduction is more pronounced compared to previously reported decreases in adult AD patients treated with dupilumab, which ranged from 53.0% to 62.9% after 1 year.⁴ Researchers suggested the higher baseline sIgE levels in children and potential age-related factors may contribute to this difference.

Although lowering sIgE levels is thought to correlate with improved clinical food tolerance, it remains uncertain whether reaching a specific threshold guarantees tolerance.While there's a single case of food tolerance development during dupilumab treatment in an adult, confirmed by oral food challenge, researchers stated that more studies are needed to assess if dupilumab raises the tolerance threshold and sustains this effect after treatment.⁵

The study concluded that future research should explore dupilumab's impact when initiated at younger ages (>6 months), possibly influencing FA development by improving skin barrier function early on and reducing pro-inflammatory cytokine release. Overall, this investigating underscored dupilumab's promising role in managing FA alongside AD in pediatric patients, emphasizing the need for further investigation into its clinical and immunological effects.

References

1. van der Rijst LP, Hilbrands MS, Zuithoff NPA, et al. Dupilumab induces a significant decrease of food specific immunoglobulin E levels in pediatric atopic dermatitis patients. Clin Transl Allergy. 2024;14(7):e12381. doi:10.1002/clt2.12381
2. Shaker MS, Schwartz J, Ferguson M. An update on the impact of food allergy on anxiety and quality of life. Curr OpinPediatr. 2017;29(4):497-502. doi:10.1097/MOP.0000000000000509
3. Brough HA, Nadeau KC, Sindher SB, et al. Epicutaneous sensitization in the development of food allergy: What is the evidence and how can this be prevented?.Allergy. 2020;75(9):2185-2205. doi:10.1111/all.14304
4. Spekhorst LS, van der Rijst LP, de Graaf M, et al. Dupilumab has a profound effect on specific-IgE levels of several food allergens in atopic dermatitis patients. Allergy. 2023;78(3):875-878. doi:10.1111/all.15591
5. Rial MJ, Barroso B, Sastre J. Dupilumab for treatment of food allergy. J Allergy Clin Immunol Pract. 2019;7(2):673-674. doi:10.1016/j.jaip.2018.07.027