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Reference: N Engl J Med. 2018 Nov 22 (level 1 [likely reliable] evidence)
The incidence of children with peanut allergy is rising. AR101 is a peanut-derived investigational biologic oral immunotherapy drug that was recently tested against placebo in a randomized controlled trial (N Engl J Med. 2018 Nov 22). Participants aged 4 to 55 years with a known peanut allergy were screened for allergic dose-limiting symptoms in response to a challenge dose of 100 mg or less of peanut protein. Those who reacted were randomized in a 3:1 ratio to receive either escalating doses of AR101 or placebo. Participants who completed the 24-week AR101 regimen then underwent a double-blind, placebo-controlled food challenge. The primary efficacy endpoint was the proportion of participants aged 4 to 17 years who could tolerate a challenge dose of 600 mg or more of peanut protein without experiencing dose-limiting symptoms (dose-limiting symptoms were based upon the attending physician’s judgment). A secondary endpoint was the ability to tolerate a challenge dose of 600 mg or more of peanut protein without experiencing dose-limiting symptoms in participants who were 18-55 years old.
Of the 496 children aged 4 to 17 years included in the trial, 372 received AR101 and 124 received placebo. Approximately two-thirds (67.2%) of the children who received the active treatment were able to ingest 600 mg or more of peanut protein during the exit food challenge without dose-limiting symptoms, compared to 4% of those who had received placebo. During the intervention period, the participants receiving AR101 had more moderate (59.7% 44.4%) and severe (4.3% vs 0.8%) events than those receiving placebo and 14% of the AR101 recipients required treatment with epinephrine compared to 6.5% of the placebo recipients. Drop out due to adverse events during the intervention period was 11.6% of those receiving AR101 compared to 2.4% in the placebo group, largely due to gastrointestinal adverse events.
During the food challenge, the participants who had received AR101 experienced less moderate (25% vs 59%) and severe (5% vs 11%) symptoms than those who had received placebo. Only 10% of participants who received AR101 required rescue epinephrine during the food challenge compared to 53% of those who had received placebo. For participants 18 to 55 years of age, the difference in rates of ability to tolerate a dose of 600 mg during the exit food challenge was not statistically different of between the active-drug group and the placebo (41.5% vs. 14.3%).
There are a few points to keep in mind about this trial. First, the purpose of the intervention is to decrease the reaction to inadvertent exposure, not to allow general consumption of peanuts. Secondly, while this trial duration was 1 year, ongoing maintenance therapy is likely to be needed to maintain the benefit. The exact nature of an optimal regimen would need to be determined. Finally, this study by its very nature required subjective adjustments to the dosing at based on the attending physician’s assessment of dose tolerance, which may be a source of bias.
Focus point: Twenty-four weeks of treatment with increasing levels of AR101 provides a significant decrease in allergic response to peanut protein, though the treatment itself is time- and resource-consuming and associated with a significant risk of adverse events.
For more information, see the topic Immunoglobulin E (IgE)-mediated food allergy in DynaMed Plus. DynaMed users click here.
DynaMed Plus EBM Focus Editorial Team
This EBM Focus was written by Sarah Dalrymple, MD, Faculty Development and Information Mastery Fellow and Clinical Instructor at the University of Virginia. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed Plus and Associate Professor in Family Medicine at the University of Massachusetts Medical School and Katharine DeGeorge, MD, MS, Assistant Professor in Family Medicine at the University of Virginia and Clinical Editor at DynaMed Plus.