Food Desensitization and SLIT

September 30, 2021
Food Desensitization and SLIT

Question
Food desensitization by SLIT is supposed to reduce the degree of sensitivity. Can we introduce SLIT for food in our routine practice? If permitted what is the suggested dose of MD/M?

Answers
From the Editors: While food desensitization has great potential it is (as we say in the USA) "not ready for prime time"

By Dr. Liz Veramendi-Espinoza: 

At present, there is no Food and Drug Administration (FDA)-approved Sublingual Immunotherapy (SLIT) to treat food allergies. In January 2020, FDA approved Oral Immunotherapy (OIT) Palforzia [Peanut (Arachis hypogaea) Allergen Powder-dnfp] to mitigate allergic reactions that may occur with accidental exposure to peanuts. The effectiveness of Palforzia was supported by a randomized, double-blind, placebo-controlled study which showed that 67.2% of Palforzia recipients tolerated a 600 mg dose of peanut protein in the challenge, compared to 4.0% of placebo recipients. The most commonly reported adverse events (AEs) were abdominal pain, vomiting, nausea, itching (including in the mouth and ears), cough, runny nose, hives, shortness of breath, and anaphylaxis (1).

Regarding SLIT, its safety profile is better than OIT, but with lower efficacy for some patients, and serum biomarkers are not available to predict which patients will benefit most from which therapy. Although rates of successful desensitization or sustained unresponsiveness are high for SLIT and especially OIT, the effects are commonly lost after treatment cessation. Consequently, it is essential to consider alternative approaches, such as adjuvants, that would augment the response and protect the individual from potential AEs (2).

SLIT protocols consist of starting doses at the microgram level and increasing to milligrams of a typical maintenance daily dose of less than 10 mg protein for up to 3 to 5 years. SLIT decreases the life-threatening risk of unintentional food exposure while maintaining a favorable safety profile with mostly transient oropharyngeal itching in less than 5% of peanut SLIT doses. Many published SLIT protocols use commercially available skin test extracts. However, it has been proposed to make SLIT by OIT solutions to improve access to consistent, economical, and customizable food desensitization (3).

At the beginning of COVID-19, several Allergy and Immunology organizations suggested deferral initiation of Food Allergen Immunotherapy, mainly focused on OIT, to decrease expose patients to hospital that subsequently may negatively affect adherence. However, as the length of this pandemic may be prolonged, recent recommendations suggest that clinicians may continue initiate and updosing. This is further supported by SLIT and low-dose OIT studies that demonstrated acceptable safety and reduction in accidental reactions, even at low doses. The final OIT dose is likely not the most important determinant of success, but rather that each dose contributes to building tolerance, irrespective of the time taken to reach the predetermined target (4,5).

References:

1. FDA approves first drug for treatment of peanut allergy for children [Internet]. FDA. FDA; 2020 [accesed september, 27th 2021]. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treatment-peanut-allergy-children
2. Nicolaides RE, Parrish CP, Bird JA. Food Allergy Immunotherapy with Adjuvants. Immunol Allergy Clin North Am. 2020;40(1):149–73.
3. Gendo K, Orden T, Tevrizian A, Jacobs J, Mozelsio N, Gilbert K, et al. Food Sublingual Immunotherapy Using Consistent, Cheaper and Customizable Oral Immunotherapy Solutions. J Asthma Allergy. 2021;14:467–70.
4. Answers to Your Questions about Administering Immunotherapy | AAAAI Education Center [Internet]. 2021 [accesed september, 27th 2021]. Available at: https://education.aaaai.org/resources-for-a-i-clinicians/immunotherapy-qa_COVID-19
5. Mack DP, Chan ES, Shaker M, Abrams EM, Wang J, Fleischer DM, et al. Novel Approaches to Food Allergy Management During COVID-19 Inspire Long-Term Change. J Allergy Clin Immunol Pract. 2020;8(9):2851–7.

Liz Veramendi-Espinoza, MD
Allergy and Clinical Immunology
Lima, Peru

By Dr. Corinne Keet

Although small studies have shown some desensitization to foods with both sublingual immunotherapy (SLIT) and oral immunotherapy (OIT), there remain many important questions about these approaches that need to be answered before they can be introduced into routine practice. The studies performed so far have been on very small groups of carefully selected patients treated in research settings, and most have not been randomized, much less blinded.

Even within these parameters, important questions about safety, efficacy and long-term outcomes have already been raised. Less data is available for SLIT specifically, and the few studies performed thus far have generally shown poorer outcomes than with OIT.(1) Whether the partially desensitized state reported in most studies of SLIT for food allergy justifies the risk of treatment has not been definitively answered; to answer this question we will need larger and longer studies that are carefully controlled and that meticulously measure adverse events.

As originally stated by Sheikh et al, and recently quoted by Sampson in a review of immunotherapy for peanut allergy: "It is important that our excitement about (the early success of OIT), which has the potential to transform the lives of millions of people worldwide, does not get the better of us, and that we wait for the science to lead the way."(2, 3)

References:

1. Narisety S. D., Keet C. A. Sublingual vs oral immunotherapy for food allergy: identifying the right approach. Drugs. 2012 Oct 22;72(15):1977-89.
2. Sampson H. A. Peanut Oral Immunotherapy: Is It Ready for Clinical Practice? The Journal of Allergy and Clinical Immunology: In Practice. 2013 January;1(1):15-21.
3. Sheikh A., Venderbosch I., Nurmatov U. Oral immunotherapy for peanut allergy. BMJ. 2010;340:c2938.

Corinne Keet, MD, MS
Assistant Professor of Pediatrics
Department of Pediatrics
Johns Hopkins School of Medicine
Baltimore, Maryland, USA

By Dr. Wesley Burks

SLIT as a treatment for food allergy has been associated with successes for kiwi, hazelnut, peach, milk, and peanut allergies. The best trial to date has evaluated SLIT in children with peanut allergy in a randomized, placebo-controlled trial. Subjects receiving peanut SLIT safely ingested more peanut during OFC than control subjects (1710 vs. 85 mg, respectively). Side effects were predominantly oropharyngeal, and epinephrine was not administered during the trial. Immunologic changes at 12 months included decreased skin prick test response size, basophil activation, and IL-5 levels with an increase in peanut-specific IgG4 levels. In a peanut SLIT trial from the CoFAR group, 70% of subjects receiving peanut SLIT were responders compared with 15% of subjects receiving placebo SLIT. The amount of peanut consumed in the peanut SLIT group increased from 3.5 to 496 mg from baseline to the 44-week OFC, respectively, with 95.2% of doses being symptom free, excluding local oral-pharyngeal symptoms. Median peanut-specific IgE levels decreased in the peanut group compared with those in the placebo group, and basophil activation did not change.

These studies show that peanut SLIT can safely induce some degree of clinical desensitization and immunomodulation among treated subjects. A consideration for the future is that the small volume, thus rendering this route of food immunotherapy more challenging if higher maintenance doses are needed to maximize efficacy, limits the maximal dose administered in SLIT. Further study is needed regarding the clinical efficacy of SLIT while maintaining its preferable safety profile.

Whether the current research with SLIT or OIT treatment for food allergy can only achieve desensitization (tolerating higher amounts of ingested food while on treatment) or can achieve tolerance has not been answered.  Much work needs to be done to answer this important question.

References:

1. Excerpted from "The changing CARE for patients with food allergy" by Jones et al. in the January 2013 issue of the Journal of Allergy and Clinical Immunology.

Wesley Burks, MD
Chairman and Chief Physician
Department of Pediatrics
University of North Carolina
Chapel Hill, North Carolina, USA

By Prof Ulrich Wahn

"Desensitization" or "specific tolerance induction" to food in cases of an established food allergy has become an interesting area of research during the last few years. Groups from the US, different European countries, Australia as well as Japan have initiated randomized controlled studies in peanut, hen’s egg as well as cow’s milk allergy, which have included primarily children. First published results are encouraging, since the concept of systematic application of minute and increasing dose of food protein via the oral or sublingual route seems to work in increasing threshold doses in comparison to placebo intervention. Obviously these protocols involve the risk of anaphylactic reactions. In addition, the documented effects need more data on long-term follow up. Therefore, oral desensitization studies should be considered as an important part of clinical research and not as routine in allergological practice.

Ulrich Wahn, PhD
Director, Berlin Charité,
Campus Virchow-Klinikum
Berlin, Germany

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