Allergy & Immunology

Food Allergies

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Early Oral Immunotherapy as a Potential Curative Treatment for Food Allergies

expert roundtables by Terri F. Brown-Whitehorn, MD; Ruchi Gupta, MD, MPH; Edwin Kim, MD, MS
Overview

Until recently, treatment options for food allergies were limited beyond allergen avoidance. Oral immunotherapy (OIT) is now used in controlled settings to increase a patient’s tolerance to allergenic foods, and research suggests that initiating OIT earlier in childhood is better.

What are the role and benefits of early OIT in patients with food allergies? Are there specific allergies that may be more responsive than others to early OIT, and, if given early enough, could OIT alter a patient's immune response enough to elicit a “cure”?
“I think that a young child's immune system is much more malleable than an adult's. Studies suggest that the earlier we initiate interventions such as OIT, the better the outcomes might be.”
— Terri F. Brown-Whitehorn, MD

I think that a young child’s immune system is much more malleable than an adult’s. Studies suggest that the earlier we initiate interventions such as OIT, the better the outcomes might be. However, OIT can be challenging in younger children who cannot always verbalize what they are thinking or feeling. Understanding the patient’s goals for immunotherapy, from tolerating accidental exposure to helping the patient outgrow the allergy, varies per patient and per food. A discussion with the patient and their family about the risks and benefits of OIT is imperative.

 

It is also important to remember that immunotherapies are very labor intensive, and the process can take months. At our institution, there is a years-long wait due to interest from so many patients. It is also important to note that OIT is not available everywhere, and, if a patient lives 5 hours away from a facility that performs OIT, for example, it is not easy for them to come in every few weeks for dose adjustments.

 

Finally, when discussing OIT with families, you also need to be aware that some children may not be great candidates, based on other diagnoses such as severe asthma, a history of severe reactions, or an inability to follow the “safety rules of OIT.” In addition, some children who start these therapies are unable to tolerate them. All these factors need to be discussed with patients and families prior to initiation.

 

I do think that there will be other options for patients over time, whether it is the use of concomitant biologics or other desensitization strategies. Sublingual immunotherapy and epicutaneous immunotherapy are available for those in research trials, but they may become clinically available over time.

“Can we reverse the allergic response by starting OIT at an early stage? There seems to be a window of opportunity where I believe we can flip the allergic response if we start early.”
— Ruchi Gupta, MD, MPH

We are currently conducting a large food allergy prevention study, and we are detecting food allergies early in high-risk infants as young as 6 months of age. What can we do while the immune system is so malleable? Can we reverse the allergic response by starting OIT at an early stage? There seems to be a window of opportunity where I believe we can flip the allergic response if we start early.

 

I recommend discussing starting OIT with families as soon as a food allergy is discovered based on the results of an oral food challenge. It is a shared decision-making process based on what families are comfortable with and would like to do. We have had good success with early OIT. We cannot call it a cure, but getting infants to increase their intake of the food allergen through OIT has worked for a lot of them. We do not know if they will relapse or if their allergy will come back, but it gives families some confidence that these patients can eat the food allergens and keep them in their diets on a regular basis. And then we follow these children to see what happens longer-term.

“We know that earlier OIT may have benefits, but there are life factors that these have to be balanced against when trying to find the ideal time to start therapy for a particular family.”
— Edwin Kim, MD, MS

We have seen data showing that responses to OIT are stronger when it is started between 1 and 3 years of age. However, I am not at the point where I am confident enough to use the word “cure.” We feel that we can change a patient’s immune system and get longer-lasting benefits. We also feel that we are definitely making steps toward a cure, but we do not know if we are there yet. So, instead, I use the words “remission” and “relapse” with patients and their families. I share with them that approximately 20% of the children from the IMPACT study who started OIT between 1 and 3 years of age were able to achieve remission lasting at least 6 months. We do not know, however, how long it may take for a relapse to occur.

 

In addition to the stronger and longer-lasting effects on the immune system in young children, another potential benefit of early OIT is from a safety standpoint. OIT can have side effects that prevent some patients from completing the therapy, but it seems that this is less common in younger children.

 

I try to be realistic and practical with families because OIT is a big commitment and is not easy to do. I try to make sure that families understand the time and effort that are involved and that they are ready to start it. It is not worth it for families to go above and beyond trying to start OIT by a certain age if they will not be able to consistently commit to it. Another consideration is a child’s eating and motor skills. If a child does not have enough eating and motor skills at 6 months, for example, we may have to wait until they are 7 or 8 months of age. We know that earlier OIT may have benefits, but there are life factors that these have to be balanced against when trying to find the ideal time to start therapy for a particular family.

 

References

Barten LJC, Zuurveld M, Faber J, Garssen J, Klok T. Oral immunotherapy as a curative treatment for food-allergic preschool children: current evidence and potential underlying mechanisms. Pediatr Allergy Immunol. 2023;34(11):e14043. doi:10.1111/pai.14043

 

Bilaver LA, Ariza AJ, Binns HJ, et al. Design of the Intervention to Reduce Early Peanut Allergy in Children (iREACH): a practice-based clinical trial. Pediatr Allergy Immunol. 2024;35(4):e14115. doi:10.1111/pai.14115

 

Durham SR, Shamji MH. Allergen immunotherapy: past, present and future. Nat Rev Immunol. 2023;23(5):317-328. doi:10.1038/s41577-022-00786-1

 

Jones SM, Kim EH, Nadeau KC, et al; Immune Tolerance Network. Efficacy and safety of oral immunotherapy in children aged 1-3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study. Lancet. 2022;399(10322):359-371. doi:10.1016/S0140-6736(21)02390-4

 

Laubach S, Kim EH, Greenhawt M, Bailey S, Anagnostou A. A review of shared decision-making, published protocols, and post-desensitization strategies in oral immunotherapy (OIT). Curr Allergy Asthma Rep. 2024;24(4):173-197. doi:10.1007/s11882-024-01132-2

 

Mack DP, Dribin TE, Turner PJ, et al. Preparing Patients for Oral Immunotherapy (PPOINT): international Delphi consensus for procedural preparation and consent. J Allergy Clin Immunol. 2024;153(6):1621-1633. doi:10.1016/j.jaci.2024.02.019

 

Upton JEM, Correa N, Eiwegger T. Oral immunotherapy for food allergy: what’s age got to do with it? Allergy. 2023;78(3):626-628. doi:10.1111/all.15623

Terri F. Brown-Whitehorn, MD

Attending Physician, Division of Allergy and Immunology
Children's Hospital of Philadelphia
Professor of Clinical Pediatrics
Perelman School of Medicine at the University of Pennsylvania
Philadelphia, PA

Ruchi Gupta, MD, MPH

    Professor of Pediatrics and Medicine
    Director, Center for Food Allergy & Asthma Research
    Northwestern University Feinberg School of Medicine
    Clinical Attending, Ann & Robert H. Lurie Children’s Hospital of Chicago
    Chicago, IL


Edwin Kim, MD, MS

    Associate Professor of Pediatrics and Medicine
    Chief, Division of Pediatric Allergy and Immunology
    Director, UNC Food Allergy Initiative
    Director, UNC Allergy and Immunology Fellowship Program
    University of North Carolina School of Medicine
    Chapel Hill, NC
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