Immunotherapy approaches for peanut allergy

ABSTRACT

Introduction: Peanut allergy has continued to increase in prevalence and despite efforts to prevent the allergy with early peanut introduction, treatments for those already with the allergy have been lacking. While the physical effects of peanut allergy have been well known, what has more recently begun to be discussed are the broad psychosocial and financial implications that are also related to the allergy. Oral (OIT), epicutaneous (EPIT), and sublingual (SLIT) immunotherapy have been developed as potential treatments for peanut allergy.

Areas covered: Pivotal clinical trials in OIT, EPIT, and SLIT from the past 10 years are reviewed in this manuscript. Peanut OIT has been shown to induce strong desensitization; however, side effects and safety of the treatment have remained a concern. Peanut EPIT has demonstrated a reassuring safety profile but with a more modest protective effect. Peanut SLIT has remained behind in development but recent studies have suggested a balance of desensitization, safety, and convenience.

Expert opinion: There are no perfect treatments for peanut allergy and OIT, EPIT, and SLIT each has its unique pros and cons. Shared decision-making between patients and providers will be essential to achieve optimal care for patients with peanut allergy.

KEYWORDS:

• Desensitization
• Epicutaneous immunotherapy
• Food Allergy
• Oral immunotherapy
• Peanut allergy
• Sublingual immunotherapy
• Sustained unresponsiveness

Article Highlights

• Peanut allergy continues to increase and the physical, psychosocial and financial burdens are significant.

• Food immunotherapy uses small increasing amounts of food allergen to desensitize patients similar to aeroallergen subcutaneous immunotherapy.

• Peanut oral immunotherapy was shown to induce strong desensitization in the majority of subjects in small studies.

• These were followed up by industry-sponsored phase 2 and phase 3 studies of peanut OIT which showed the majority of subjects to be desensitized above 1000 mg of peanut protein.

• Increased risk of allergic reactions and anaphylaxis with peanut OIT has been a concern.

• GI side effects are frequent with peanut OIT although the actual risk of eosinophilic esophagitis remains unclear.

• Peanut EPIT has been studied across two phase 2 studies and a large phase 3 study.

• The majority of subjects have local side effects but treatment discontinuation from side effects was rare.

• Although phase 2 studies showed clinical benefit, the phase 3 study did not meet its primary statistical endpoint.

• Peanut SLIT induces desensitization in the majority of subjects although to a lower absolute threshold than peanut OIT.

• Dosing symptoms with peanut SLIT were mostly from transient oropharyngeal itching and symptoms requiring treatment or leading to treatment discontinuation were rare.

• OIT, EPIT, and SLIT for peanut allergy have unique pros and cons regarding desensitization, safety, and convenience. Shared decision-making around these risks and benefits will be essential as the treatments move forward.

Declaration of interest

EH Kim reports consultancy with Aimmune therapeutics, DBV technologies, AllerGenis, Allakos, Ukko, Vibrant America; clinical medical advisory board membership with DBV Technologies. Grant funding has been received from the NIH-NIAID, NIH-NCCIH, FARE and the Wallace Research Foundation. AW Burks reports minority stockholder in Allertein, Mastcell Pharmaceuticals; advisory board membership with Aimmune Therapeutics Inc, Consortia TX Inc, Prota therapeutics Pty Ltd; consultancy for Astella Pharma Global Development, DBV Technologies S.A., Kaleo, N-fold LLC, Ukko Inc; royalties with UpToDate; sponsored research with FARE, NIH. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One of the peer reviewers has declared that they have been employed by Laboratorios LETI S.L. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.