For Some Toddlers, Oral Immunotherapy Led to Remission for Peanut Allergy

For children under 3, there might be a chance to intervene and spur remission in peanut allergy through oral immunotherapy (OIT), according to results of a major study released Thursday, and some allergists said it is time to make this therapy immediately available, given the substantial burden of peanut allergy.

Although other studies have shown that desensitization to food allergy, including peanut allergy, is possible through OIT—in which patients ingest tiny but gradually increasing amounts of the food they are allergic to over time—creating remission, or sustained unresponsiveness, has been harder to achieve.

Results of the randomized, double-blind, placebo-controlled trial were published in The Lancet,¹ and in an accompanying editorial, the authors, all allergy-immunology specialists, called for “immediate real-world implementation” in this age group, and noted that pharmaceutical OIT products, while an option, are not a necessity since this study used low-cost, store-bought peanut flour.²

The study found that 1 in 5 children were able to eat peanut freely after staying off OIT for 26 weeks, and the younger they were at the time they started OIT, the better they did. Most also achieved desensitization, meaning that they could tolerate small amounts of peanut before progressing to a severe allergic reaction.

The trial, called IMPACT and funded by the National Institute of Allergy and Infectious Disease, was conducted at 5 food allergy research centers in the United States and included 146 children, aged 1 to 3 years, allergic to peanut. To qualify for entry into the study, they had to react to 500 mg or less of peanut protein during a double-blind, placebo-controlled food challenge (DBPCFC) to prove that they were truly allergic.

By random 2:1 assignment, 96 children were placed in the peanut OIT group and 50 to the placebo group. The intervention in the OIT group was commercially available peanut flour, and the placebo was oat flour.

For 2.5 years, or 134 weeks, participants in both groups ingested doses that gradually increased from 0.1 mg to 2000 mg (equivalent to roughly 6 peanuts) at home, except for when the doses were increased; these initial higher doses were done in the research center. The OIT protocol was divided into 4 phases:

• The initial dose escalation from 0.1 mg to 6.0 mg.
• A build-up phase every 2 weeks to a maximum target dose of 2000 mg peanut daily, the equivalent of 6 peanuts, from week 0 to week 30), with children needing to reach a minimum dose of 250 mg daily in order to move on to the daily maintenance phase.
• Daily OIT maintenance from weeks 30 to 134; at 134 weeks, there was a 5000 mg DBPCFC, the equivalent of 16 peanuts.
• Therapy was stopped from weeks 134 to 160, and at week 160, participants were tested again in another DBPCFC with 5000 mg of peanut.

Seventy children in the peanut group and 23 in the placebo group made it to week 160.

Findings

Researchers said this was the largest and longest study to enroll toddlers, and the results showed that at week 134, significantly more participants were desensitized to peanut: 71% (68/96) of the children in the peanut OIT group compared with 1 child in the placebo group (95% CI, 61-80 vs 95% CI, 0.05-11; risk difference [RD], 69%; 95% CI, 59%-79%; P < .0001).

By week 160, after avoiding peanut, 21% (20/96) in the peanut group achieved remission compared with 1 child in the placebo group (95% CI, 13-30 vs 0.05-11; RD, 19%, 95% CI, 10%-28%; P = . 0021).

The benefits of starting OIT stood out by age, as the youngest were more likely to reach remission: 71% of 1-year-olds, 35% of 2-year-olds, and 19% of 3-year-olds.

Even children who did not reach the point of remission could still tolerate more peanut protein, the equivalent of 6 to 12 peanuts, at week 160. Only 4% in the placebo group could do that, the researchers said.

In addition, the study provided valuable information about biomarkers that correspond to peanut allergy, the researchers said.

Reactions During the Study

While most participants had at least 1 dosing reaction, most reactions were mild to moderate; they were more frequent in the OIT group but still happened with those taking the placebo (98% vs 80%, respectively).

The most common reactions were skin related, including hives, rashes, and flushing (88% vs 58%); gastrointestinal (GI), including stomach pain and itching in the mouth (78% vs 54%); and respiratory, including rhinitis, coughing, and wheezing (75% vs 44%).

As eosinophilic esophagitis (EOE) is a rare but known possibility with OIT, the researchers monitored GI symptoms via a modified but not validated questionnaire to determine whether additional action was needed if symptoms continued. Three of the 96 children in the peanut OIT group were referred for evaluation and endoscopy; 2 saw symptoms resolve after OIT was discontinued and 1 had persistent EOE.

The researchers noted several limitations. There was a high dropout rate between weeks 134 and 160, "with a substantial differential between treatment groups that might have affected the outcome." There was a small number of children younger than age 2, which resulted in larger confidence intervals for the chance of reaching sustained unresponsiveness for that age group. In addition, while the maximum daily OIT amount was 2000 mg in the maintenance period, only 27% in the peanut group and 20% of the placebo group reached that amount, which might have affected outcomes.

In the accompanying editorial, the authors touted the study's safety and efficacy findings and while they noted that there is an existing FDA-approved peanut OIT product on the market, they urged adoption of early OIT in this age group, given the psychological and financial burdens of peanut allergy.

The product, Palforzia, is approved for patients aged 4 to 17 years.

“Waiting for regulatory approval for commercial products for very young children for this treatment to be deemed ready does not benefit families,” the authors wrote. “Commercial products represent an option to choose but are not a necessity when the flour used in IMPACT is cheap and widely available for purchase in stores and online.”

References

1. Jones SM, Kim EH, Nadeau KC, et al. 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;399:359-371.

2. Greenhawt M, Shaker M, Abrams EM. Peanut oral immunotherapy in very young children. Lancet. 2022;399:336-337.