expert roundtables

Oral Immunotherapy: Effectiveness, Tolerability, and Treatment Goals

by Aikaterini Anagnostou, MD, PhD; David M. Fleischer, MD; and Robert A. Wood, MD

Overview

For many parents, the goal of oral immunotherapy (OIT) is to provide their children with a layer of protection against severe reactions that may occur with accidental food allergen ingestion. A detailed understanding of the process, risks, and benefits of OIT is crucial before initiating therapy.

Q:

What should parents, children, and clinicians know about OIT? 

David M. Fleischer, MD

Section Head, Allergy and Immunology
Professor of Pediatrics
Director, Allergy and Immunology Center
Children’s Hospital Colorado
University of Colorado Denver School of Medicine
Aurora, CO

“It is very important that the treatment goals and expectations for children with food allergies are realistic. We may spend an hour (or even longer) with families going over everything in detail before we decide to move forward with OIT.”

David M. Fleischer, MD

It is very important that the treatment goals and expectations for children with food allergies are realistic. We may spend an hour (or even longer) with families going over everything in detail before we decide to move forward with OIT. OITs can desensitize patients, which we explain during our discussions with families. In this desensitized state, OIT may provide protection from allergic reactions due to accidental allergen exposures. Mathematical models suggest that, if you establish a tolerated dose of 300 mg, a patient is likely protected against the smallest of accidental exposures to products due to cross-contaminated allergens in processed foods. However, studies show that patients on OIT may lose this protection once treatment stops, and this protection can go away in as little time as a few weeks. Therefore, as far as we know now with OIT, treatment needs to continue indefinitely to maintain desensitization. 

Although the goal of desensitization is realistic for many patients, tolerability needs to be considered to determine whether a child is an optimal candidate for OIT. The benefits of possibly being desensitized with daily peanut maintenance therapy need to be weighed against the risks of having a systemic reaction. According to studies and meta-analyses, children on peanut OIT are 2 to 3 times more likely to have a systemic reaction while on OIT than those who avoid peanuts. In the study that supported the first US Food and Drug Administration approval of a peanut OIT, approximately 15% of patients had a systemic reaction at some point during therapy. And a person’s experience with OIT, once initiated, can also play a role in whether you decide to continue with the therapy.

When starting OIT in a child who is a bit older and has lived with the allergy for some time, there can be a disconnect at first. We have been telling these patients and their parents to read labels and to make sure that the child avoids certain foods, otherwise the child could have a life-threatening reaction. And then, all of a sudden with OIT, the idea changes to instructing patients and parents that the child must eat that food every day, albeit in the small amounts given in maintenance dosing. So, you have to be clear about what you are doing, set realistic goals, and understand that OIT may need to be discontinued if it is no longer beneficial for either the child or the parents. 

Aikaterini Anagnostou, MD, PhD

Professor of Pediatrics
Director, Food Immunotherapy Program
Director, Food Challenge Program
Co-Director, Food Allergy Program
Lead, Adolescent Transition for Allergy
Texas Children’s Hospital
Baylor College of Medicine
Houston, TX

“A key benefit for many families is that they no longer need to guard against trace exposures. Of course, this does not eliminate the need for checking labels and carrying emergency medication. So, a balanced discussion about both the risks and benefits of OIT is required, and this often needs to be an ongoing discussion.”

Aikaterini Anagnostou, MD, PhD

I agree with the importance of providing families with a realistic overview of what OIT entails in terms of risks and potential benefits. Realistic expectations should be established from the outset. Even in children who are successfully desensitized and are on maintenance therapy, we still recommend allergen avoidance. The expectation should not be that they will be able to eat as many peanuts (or other allergen[s]) as they want, whenever they want.

Nonetheless, allergists should also be clear about the potential benefits of OIT. An emerging body of evidence shows that quality of life can improve after successful desensitization. Social and dietary restrictions relax, and there is a lot less fear about the child being outside the home in environments where they might have an accidental exposure and reaction. A key benefit for many families is that they no longer need to guard against trace exposures. Of course, this does not eliminate the need for checking labels and carrying emergency medication. So, a balanced discussion about both the risks and benefits of OIT is required, and this often needs to be an ongoing discussion.

Adherence is always challenging. Many people have trouble adhering to a 7-day course of oral antibiotics, let alone taking a treatment every day indefinitely. Children may view the food given as medicine if it is a food that they do not enjoy eating, and adherence is very difficult if a child does not like the food but is told to eat it every day. Restrictions associated with OIT can also affect adherence. Many patients do not want to worry about not being able to exercise for 30 minutes before and for 2 hours after OIT dosing. It takes a motivated, disciplined individual to remain on OIT, but, on the other hand, there are multiple success stories involving children who participated in research studies and are now in college and are remaining compliant.

Robert A. Wood, MD

Julie and Neil Reinhard Professor of Pediatric Allergy and Immunology
Professor of Pediatrics and International Health
Director, Eudowood Division of Allergy, Immunology and Rheumatology
Director, Pediatric Clinical Research Unit
Deputy Director, Institute for Clinical and Translational Research
Johns Hopkins University School of Medicine
Baltimore, MD

“OIT does not reduce the risk of reactions to 0, and this is true for any food allergy.”

Robert A. Wood, MD

A point that has yet to be touched upon is that there may be very different goals of OIT for different foods. For peanuts and tree nuts, for example, the vast majority of parents are very happy if their child is protected against reactions to small accidental exposures. The children usually have very little interest in ever eating those foods in larger quantities. With milk and eggs, which are allergies that are more likely to resolve on their own, there is often a different goal of being able to incorporate the food(s) into the diet more regularly.

OIT does not reduce the risk of reactions to 0, and this is true for any food allergy. To my knowledge, in long-term follow-up studies 5 to 10 years out, some patients still experience intermittent reactions. We hope for sustained unresponsiveness, but we do not have the data to indicate that this can realistically be achieved. There may be the occasional patient who does achieve this, but we currently tell people that, for lifetime protection, they may need to take maintenance OIT for life.

Additionally, many patients who started OIT years ago have decided to go back to strict avoidance because they felt that avoidance was far preferable to eating the food every day. Many peanut-allergic children who go off to college decide to discontinue OIT. In fact, they often quit within the first month because they find that avoiding peanuts is much easier than having peanuts every day. And it is not just peanut allergies. I recall a long-term study of milk OIT, for which investigators thought that the results would be better because children who had been desensitized would be able to eat pizza. Early on, patients were eating a significant amount of milk products in a dietary form, but 25% of patients went back to strict avoidance just 5 years later. So, there is a lot that we need to learn about how to make OIT safer and more patient friendly, and it is important to remember that many families find OIT to be very difficult and challenging.

References

Anagnostou A. Weighing the benefits and risks of oral immunotherapy in clinical practice. Allergy Asthma Proc. 2021;42(2):118-123. doi:10.2500/aap.2021.42.200107

Rigbi NE, Goldberg MR, Levy MB, Nachshon L, Golobov K, Elizur A. Changes in patient quality of life during oral immunotherapy for food allergy. Allergy. 2017;72(12):1883-1890. doi:10.1111/all.13211

Vickery BP, Berglund JP, Burk CM, et al. Early oral immunotherapy in peanut-allergic preschool children is safe and highly effective. J Allergy Clin Immunol. 2017;139(1):173-181.e8. doi:10.1016/j.jaci.2016.05.027

Vickery BP, Vereda A, Casale TB, et al; PALISADE Group of Clinical Investigators. AR101 oral immunotherapy for peanut allergy. N Engl J Med. 2018;379(21):1991-2001. doi:10.1056/NEJMoa1812856

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