Young patients with peanut allergy who received the immunotherapy treatment AR101 became tolerant to peanut over time, protecting themselves from accidental ingestion, according to phase 3 trial findings presented at the American College of Allergy, Asthma and Immunology Annual Scientific Meeting.
The findings were published simultaneously in The New England Journal of Medicine.
“Previous studies have suggested that oral immunotherapy is a potential strategy for the treatment of allergy by inducing desensitization, which is generally understood as a transient upward shift in threshold reactivity to an allergen as a result of ongoing controlled exposure to that same allergen,” Brian P. Vickery, MD, associate professor of pediatrics in the Emory University School of Medicine, and members of the PALISADE Group of Clinical Investigators, wrote.
“Since the evidence from multiple early-stage trials is limited by small sample sizes and differing methods, most practice guidelines current recommend against oral immunotherapy in routine clinical settings,” they added.
Researchers randomly assigned 551 patients aged 4 to 55 years (496 aged 4 to 17 years) with peanut allergy in a 3:1 ratio to receive an escalating dose of AR101 (Aimmune Therapeutics) or placebo. Those who completed the regimen (300 mg per day for approximately 24 weeks) participated in a double-blind, placebo-controlled food challenge at the end of the trial.
Vickery and colleagues found that during the challenge, 250 of the 372 patients aged 4 to 17 years who received AR101 were able to ingest at least 600 mg of peanut protein without dose-limiting symptoms vs. only five of the 124 patients aged 4 to 17 who received placebo. The maximum severity of symptoms was moderate in 25% of those who received AR101 (vs. 59% of those who received placebo) and severe in 5% of those who received AR101 (vs. 11% of those who received placebo). Adverse events during the intervention — most of them moderate in those who received AR101 — occurred in more than 95% of all participants aged 4 to 17 years. Efficacy was not observed in patients older than 18 years.
“We’re excited about the potential to help children and adolescents with peanut allergy protect themselves against accidentally eating a food with peanut in it,” Stephen Tilles, MD, ACAAI past president, advisor for Aimmune Therapeutics and study co-author said in a press release.
“Our hope when we started the study was that by treating patients with the equivalent of one peanut per day, many would tolerate as much as two peanuts. We were pleased to find that two-thirds of the people in the study were able to tolerate the equivalent of two peanuts per day after 9 to 12 months of treatment, and half the patients tolerated the equivalent of four peanuts,” he added.
Jay Lieberman, MD, vice chair of the ACAAI Food Allergy Committee and another study co-author, urged caution.
“This is not a quick fix, and it doesn’t mean people with peanut allergy will be able to eat peanuts whenever they want. But it is definitely a breakthrough. The hope would be to have a treatment available in the second half of 2019. If that happens, people who receive and are able to tolerate this treatment should be protected from accidental exposures.”
In a related editorial, Michael R. Perkin, PhD, of the Population Health Research Institute at the University of London, further elaborated on the adverse events tied to the highly-anticipated AR101.
“Desensitization was not easy on the patients. Side effects during the intervention period that led to withdrawal from the trial occurred in 11.6% of the participants in the active-drug group and in 2.4% of the control group. This is not something to start at home,” he wrote.
“Epinephrine was used by 14% of the participants in the active-drug group as a result of reactions to the treatment. The longer-term side effects of sustained consumption of an allergen to which the body has produced IgE antibodies remain unknown. Current thinking has focused on eosinophilic disease, such as eosinophilic esophagitis, but surveillance and follow-up will be crucial.” – by Janel Miller
Disclosures: Please see the study and editorial for the authors’ relevant financial disclosures.