Children under 4 years of age with peanut allergies had significantly higher desensitization and remission rates with oral immunotherapy versus placebo, and younger age appeared to predict better outcomes, the randomized IMPACT study showed.
Among 146 children ages 1 to 3 years, 71% of those assigned to peanut flour oral immunotherapy became desensitized to a 5,000 mg peanut exposure at week 134, as compared with 2% of kids assigned to a placebo flour (risk difference [RD] 69%, 95% CI 59-79, P<0.001), according to Stacie Jones, MD, of Arkansas Children’s Hospital in Little Rock, and collaborators.
And 21% of participants on the oral immunotherapy achieved remission, or sustained desensitization, at the 160 week mark, versus 2% of the placebo patients (RD 19%, 95% CI 10-28, P=0.0021), the study group reported in The Lancet.
Two factors predicted a higher likelihood of remission: younger age at screening (odds ratio [OR] 0.93 per month increase, 95% CI 0.88-0.99, P=0.022) and lower baseline peanut-specific IgE (OR 0.12 per tenfold increase, 95% CI 0.03-0.46, P=0.0017).
The results “suggest a window of opportunity for more successful interventions at an early age in the course of peanut allergy,” the study authors wrote.
Currently, there are no approved peanut immunotherapies for this age group. The only oral immunotherapy for peanut allergies approved by the FDA is for children ages 4 to 17 years. The American Academy of Pediatrics, meanwhile, recommends that infants be exposed to peanuts as early as 4 months of age to reduce the risk of allergies, but these guidelines have not caught on.
“Early childhood peanut oral immunotherapy is, in our view, ready for immediate real-world implementation, given evidence of higher efficacy and similar safety to oral immunotherapy for older individuals,” argued Matthew Greenhawt, MD, of the Children’s Hospital of Colorado, and colleagues, writing in a corresponding editorial.
“Waiting for regulatory approval for commercial products for very young children for this treatment to be deemed ready does not benefit families,” Greenhawt and colleagues continued. “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.”
In the U.S., approximately 2% of children have a peanut allergy, according to the study, and these children run the risk of accidental exposure and anaphylaxis.
From August 2013 to October 2015, IMPACT randomized 146 children ages 1 to 3 years at five academic medical centers across the U.S. to either the peanut powder (made by the Golden Peanut Company) or an oat flour placebo, in a 2:1 ratio.
Children were screened for a history of peanut allergy, peanut-specific IgE levels of 5 kUA/L or higher, a skin prick test wheal size greater than that of saline control by 3 mm or more, and a positive reaction to a cumulative dose of 500 mg or less of peanut in a blinded food challenge. Participants were excluded if they had a history of severe anaphylaxis to peanuts, uncontrolled asthma, or uncontrolled atopic dermatitis, among other criteria.
Participants in the study went through a four-phase protocol:
- Initial dose escalation (0.1-6.0 mg)
- Weeks 0-30: a build-up every 2 weeks to a maximal target dose of 2,000 mg peanut daily
- Weeks 30-134: daily maintenance
- Weeks 134-160: oral immunotherapy discontinuation
At 134 weeks and 160 weeks, participants were evaluated by a double-blind, placebo-controlled food challenge with 5,000 mg of peanut powder.
For children who received the peanut powder, five of seven participants (71%) ages 1 to 2 years achieved remission, while eight of the 43 participants (19%) who were 3 years old did.
Study participants also underwent immune assessments throughout the study period. A lower peanut component-specific IgE to Ara h6 ratio predicted desensitization (OR 0.35 per 10-fold increase, 95% CI 0.12-0.99, P=0.048).
Of the 96 participants randomized to peanut flour, 70 completed the immunotherapy course. Of the 50 assigned to placebo, only 23 completed the 160-week course. The researchers noted that the participants who discontinued before completing the week 160 food challenge had a higher skin prick test to peanut at screening than that of participants who completed the whole course (17.0 mm vs 14.5 mm, P=0.012).
The median age of the participants was 39.3 months, 65% percent were white, and 68% were boys.
Jones’ group cautioned that while the study looked at children ages 1 to younger than 4 years, only 12% of children were between 1 and 2 years old. They also acknowledged that there was a high dropout rate during the last phase of the study, especially in the placebo arm, that may have impacted the results.
The study was funded by the National Institute of Allergy and Infectious Disease and the Immune Tolerance Network.
Jones reported grants or fees from or other relationships with Aimmune Therapeutic, Astellas, DBV Technologies, EMMES Corporation, Food Allergy Research & Education, Genentech, the NIH, Regeneron, and Sanofi.
Greenhawt reported consulting for Aquestive and personal fees from DBV Technologies, Sanofi/Regeneron, Genentech, Nutricia, Novartis, Aquestive, Allergy Therapeutics, Pfizer, US WorldMeds, AllerGenis, ALK-Abello, AstraZeneca, Aravax, and Prota.