A clinical trial funded by the National Institutes of Health found that giving oral peanut immunotherapy to highly peanut-allergic children aged 1 to 3 years safely desensitized most of them to peanut. and induced remission of peanut allergy in a fifth. Immunotherapy consisted of a daily oral dose of peanut flour for 2.5 years. Remission was defined as being able to eat 5 grams of peanut protein, equivalent to 1.5 tablespoons of peanut butter, without having an allergic reaction six months after completing immunotherapy. Younger children and those who started the trial with lower levels of peanut-specific antibodies were most likely to achieve remission. The results of the trial, called IMPACT, were published today in the journal The Lancet.
“The landmark results from the IMPACT trial suggest a window of opportunity in early childhood to induce peanut allergy remission through oral immunotherapy,” said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH. “We hope these study results will inform the development of treatment modalities that reduce the burden of peanut allergy in children.” NIAID sponsored the trial and funded it through its Immune Tolerance Network.
Peanut allergy affects approximately 2% of children in the United States, or nearly 1.5 million people aged 17 and under. The risk of a life-threatening allergic reaction to an accidentally eaten peanut is significant for these children, most of whom remain allergic to peanuts for life.
In designing the study, researchers in the IMPACT trial believed that oral immunotherapy had the potential to alter the immune system, providing oral peanut immunotherapy early in life, when the immune system is still maturing, could alter a child’s immune response to peanuts. Two previous studies have provided proof of concept that oral peanut immunotherapy could be safely given to very young children and have a therapeutic effect.
Nearly 150 children ages 1 to 3 participated in the IMPACT trial at five academic medical centers in the United States. Only children who had an allergic reaction after eating half a gram of peanut protein (about 1.5 peanuts) or less were eligible to participate in the study. Children were randomly assigned to receive either flour containing peanut protein or a similar-appearing placebo flour. Flours were mixed into foods such as applesauce or pudding to help mask their taste. No one except a site pharmacist and a site dietician knew who had received peanut flour or placebo flour until all the data had been collected and the study visits are completed.
Over a 30-week period, the children in the treatment group ate gradually increasing daily doses of up to 2 grams of peanut protein, which is equivalent to about six peanuts. The children then continued on their daily dose of peanut flour or placebo for two more years.
Next, the children underwent an oral food challenge in which they received gradually increasing doses of peanut protein to a cumulative maximum of 5 grams. They then stopped treatment and avoided peanuts for six months.
Finally, the children were given a new oral food challenge with 5 grams of peanut protein, which is equivalent to about 16 peanuts. Those who did not have an allergic reaction during the challenge were then fed 8 grams of peanut butter, equivalent to 2 tablespoons, on another day to confirm that they could eat peanuts without having an allergic reaction.
At the end of the treatment period, 71% of the children who had received peanut flour were desensitized to peanut, compared to only 2% of those who had received the placebo flour. Desensitization was defined as being able to eat 5 grams of peanut protein on the first oral food challenge without having an allergic reaction. After six months of peanut avoidance after treatment, 21% of children who received peanut flour could eat 5 grams of peanut protein during the second oral food challenge without having an allergic reaction and were therefore in remission. In contrast, only 2% of children who received placebo flour were in remission at that time.
Investigators found that lower levels of peanut-specific immunoglobulin E antibodies at the start of the trial and being younger predicted whether a child would achieve remission. In an analysis done after the investigators were able to look at the study data, they found an inverse relationship between age at the start of the trial and remission, with 71% of 1-year-olds, 35% of 2-year-olds and 19% of 3-year-olds in remission.
Although almost all children who received peanut flour had at least one dose-related reaction during treatment, most reactions were mild to moderate in intensity. Twenty-one children received the rescue medication epinephrine for 35 moderate reactions to peanut flour during the 2.5-year treatment period.
The Immune Tolerance Network conducted the trial under the direction of A. Wesley Burks, MD, and Stacie M. Jones, MD Dr. Burks is chief executive of UNC Health, dean of the UNC School of Medicine, and vice chancellor for medical affairs at the University of North Carolina at Chapel Hill. Dr. Jones is a professor of pediatrics at the University of Arkansas for Medical Sciences and at Arkansas Children’s Hospital in Little Rock.
More information about the IMPACT trial is available at ClinicalTrials.gov under study identifier NCT01867671 (https://www.clinicaltrials.gov/ct2/show/NCT01867671).