Ushering in a new era in food allergy management with EAACI guidelines

Abstract

In 1908, Alfred Schofield described treating a 13 year old with severe egg allergy with increasing amounts of egg for “establishing tolerance to this special poison.”¹ In 2014, the EAACI guidelines stated that food immunotherapy was not recommended for routine clinical use.² In 2018, an incredible 110 years following the first description of egg oral immunotherapy (OIT), the EAACI immunotherapy guidelines³ recommended OIT as a treatment option to increase the threshold for children with egg, milk, or peanut allergy. These 2018 Guidelines acknowledged sublingual (SLIT) and epicutaneous (EPIT) immunotherapy but could not recommend them.

Another historic delay in acquiring evidence to recommend a food allergy treatment relates to anti-IgE biologics. In 2003, Leung et al.⁴ reported that TNX-901 raised the threshold of reaction from approximately ½ to about 9 peanuts. My recollection of discussions around that time, not aligned with my views, included concerns about the approximately 25% of poor or nonresponders and whether it is prudent to administer a therapy that may give a false sense of security. Back then, the cup was half empty, and shared decision-making was not central to patient care. For conspiring reasons, drug development was delayed. The 2014 EAACI guidelines stated that anti-IgE alone or in combination with immunotherapy was not recommended,² and the 2018 EAACI immunotherapy guidelines³ did not offer recommendations, only mentioning that combining anti-IgE (omalizumab) with immunotherapy may enhance safety. Unlike the century of experience before the approval of an OIT product, approval of omalizumab—in the United States—came a “mere” two decades after the initial publication of an anti-IgE biologic.

In this issue, the EAACI Guidelines on the Management of IgE-Mediated Food Allergy⁵ ushers in a new era of hope and options for our patients, empowerment for allergists in treating people with food allergies, but also very significant implementation challenges involving multiple entities and overcoming rampant health disparities. Building substantially from a 2024 systematic review,⁶ and involving a diverse panel of international experts and stakeholders, applying GRADE methodology, layers of review, and considering publications that came after the systematic review, 14 recommendations are provided. Some recommendations substantially support prior ones (e.g., that allergen-specific immunotherapy is recommended under the guidance of an experienced team), some imbue important new nuances (e.g., emphasizing training about anaphylaxis management through transition periods of adolescence and adulthood), and some recommendations are entirely new.

There is a notable new recommendation encouraging the inclusion of tolerated foods in the diet. This important message encapsulates our understanding that overtesting and delayed ingestion of allergens can result in unnecessary avoidance with negative nutritional, immunologic, and psychosocial consequences, and that ingestion has a role in prevention. The recommendation for age-appropriate individualized dietary advice, ideally including a dietitian, especially for complex patients, has been made previously,² but here the recommendation emphasizes aspects beyond simply education. The recommendation importantly highlights the need to address economic issues, health disparities, food insecurity, and other barriers to dietary care, as well as the importance of addressing mental health needs. In fact, there is also a crucially important new recommendation focusing on the importance of psychological support.

Regarding OIT, the new guidelines align substantially with the 2018 EAACI immunotherapy guidelines³ in describing peanut, egg, and cow's milk OIT for desensitization in children and adolescents but use the terms “recommended” for peanut and “suggested” for egg and milk based on the data. Notably, the guidance includes an age constraint, “generally above 4 years of age,” for egg and milk that was also in the 2018 guidance with a stricter age cut-off terminology, and for all three foods. The lower age constraint is now removed for peanuts. Additionally, the expert panel offers insights about the age constraint explaining that treatment is targeted to those with likely persistent allergy where OIT is more warranted, a phenotype that could be recognized under age 4 years.

New in this Guideline are three treatment recommendations that are nuanced by circumstances of available evidence and include discussions of studies published after the systematic review.⁶ For peanut allergy, SLIT is suggested to achieve desensitization in children and adolescents, and for EPIT, the same recommendation is stated with the additional comment, “if available”. Discussions around these treatments are brief. One wonders if eventually there will be some upper-age constraints for starting EPIT. The discussion around SLIT interestingly includes verbiage that a standardized regulatory-approved product would “probably be more amenable” for use than actual food, but pathways for using alternatives in clinical practice are also described.

Regarding omalizumab, availability is a major constraint, and the recommendation is straightforward: “In patients with IgE mediated food allergy, omalizumab is suggested to achieve desensitization.” This is perhaps the biggest milestone in food allergy treatment, admittedly with a mountain of details yet to be worked out.⁷

The nature of guidelines is to focus on what we can say something about based on available data. This guideline came before a needle-free, nasal spray option for epinephrine was approved in some countries and so it only describes injected epinephrine. This guideline does not discuss the many therapeutic options that might work for a spectrum of age groups, foods, or treatment approaches but has not had enough study upon which to make a recommendation. It is exciting to discuss these options with patients and hope for the day when more data are available.⁸

The authors present a table describing and prioritizing gaps in evidence, most being “high priority.” This is both exhilarating for opportunity and frustrating for the work ahead, and the list could have been longer—maybe a good problem to have. Personalizing care will require the identification of phenotypes and endotypes that respond optimally to specific approaches. Identification of biomarkers for optimizing care is a gap that did not make the list but should. Baseline threshold, particularly therapeutic opportunities for those with a high threshold, is an identified gap that deserves special attention, especially as pricey therapeutics emerge.⁹ The future work in this field is substantially going to be around personalization. We will need a Guideline for that.

This editorial was not funded.

SH Sicherer reports royalty payments from UpToDate and from Johns Hopkins University Press; grants to his institution from the National Institute of Allergy and Infectious Diseases, Pfizer, Inc., and Food Allergy Research and Education; and personal fees from the American Academy of Allergy, Asthma, and Immunology as a Deputy Editor of the Journal of Allergy and Clinical Immunology: In Practice, outside of the submitted work.