AAAAI Virtual Annual Meeting 2021: Promising Results for Peanut Sublingual Immunotherapy in Toddlers
Findings from FARE-funded research on a peanut-based immunotherapy are among the meeting highlights.
The American Academy of Allergy, Asthma & Immunology (AAAAI) held its annual meeting as a virtual event from February 26 to March 1. We are encouraged by the scientific progress made in the face of the past year’s challenges and are proud to showcase standout examples of FARE-driven research presented at AAAAI 2021.
Sublingual (“beneath the tongue”) immunotherapy, or SLIT, is an allergen-based therapy that has been used to treat allergies to kiwi, peanut, hazelnut, milk and peach. Allergen is dissolved in a small amount of liquid and held under the tongue for several minutes before being spat out or swallowed. This introduces undigested allergen to cells in the lining of the mouth that promote food tolerance. Compared to oral immunotherapy (OIT), SLIT uses smaller doses because the amount of liquid that fits under the tongue is limited. Early research suggests that SLIT may be better tolerated than OIT, resulting in fewer and milder reactions.
Published in 2019 and funded in part by FARE, a small University of North Carolina (UNC) study in children aged 1-11 reported promising results for extended treatment with peanut SLIT for up to five years. Two-thirds of the children who enrolled, and 87 percent of those who received three to five years of peanut SLIT, were able to tolerate eating at least 750 mg peanut protein (about 2.5 to 3 peanut kernels*). Building on this work, a FARE-funded study by researchers at UNC and University of Texas Southwestern Medical Center examined the effectiveness of peanut SLIT as an early intervention for toddlers with peanut allergy. Results from this study were presented at AAAAI 2021 (Abstract L2).
Over 36 months, 50 peanut-allergic children aged 1-4 years received either daily peanut SLIT or placebo. The children who received peanut SLIT eventually reached a daily maintenance dose of 4 mg peanut protein, equivalent to a small peanut crumb. By comparison, the daily maintenance dose for the peanut oral immunotherapy product Palforzia is 300 mg peanut protein, or a large peanut kernel.
Four measures of desensitization were reported:
- The number of children who passed the food challenge after treatment, eating the full challenge dose without having a reaction. (None of the children were able to pass the food challenge before treatment.)
- The total amount of peanut protein that the children could eat without reacting, before and after treatment
- The diameter of the children’s wheals (welts) in response to skin prick tests, before and after treatment
- The number of children who passed the food challenge when it was repeated three months after treatment ceased
Thirty-six children completed a double-blind, placebo-controlled food challenge at completion of the 36-month treatment. Among the 19 children who completed the challenge after receiving peanut SLIT, 14 tolerated the full challenge dose of 4,443 mg peanut protein, or 15 to 18 peanut kernels. None of the 17 children in the placebo group tolerated the full challenge dose.
The median cumulative dose of peanut protein is the total amount of protein eaten by the child who tolerated more protein than one-half of the group and less protein than the other half of the group. With more than half of the children who received peanut SLIT passing the food challenge, the group’s median cumulative dose was the challenge dose of 4,443 mg, up from 143 mg before treatment. This change – from half of a peanut kernel to a generous handful of peanuts – is a remarkable increase of more than 3,000 percent. By comparison, the median cumulative dose for the placebo group increased by 230 percent, from a 43-mg fragment of peanut to 143 mg, or about half of a kernel.
Peanut SLIT also resulted in smaller wheals during skin prick tests. Over the course of treatment, the average wheal diameter fell by 65 percent for the peanut SLIT group but grew by 4 percent for the placebo group.
Three months after treatment ended, the children had another food challenge to test for sustained unresponsiveness (SU), which is desensitization that endures for a period of time after treatment is discontinued. Here again, peanut SLIT significantly outperformed placebo. Twelve children in the peanut SLIT group passed the challenge, compared to two children in the placebo group.
Of more than 20,000 doses taken during the course of the trial, symptoms were reported for 1,031 doses of peanut SLIT and 629 placebo doses. No reactions requiring epinephrine were mentioned.
While this trial was small, the impressive results indicate that peanut SLIT should be explored further as an early intervention. We look forward to future investigations of this promising treatment for peanut allergy.
*A typical peanut pod contains two kernels.