Peanut Desensitization Falls 1 Month After Avoiding Exposure
Children with peanut allergies treated with peanut oral immunotherapy for 3 years can tolerate increasingly higher exposures to peanuts. But avoidance of peanut-protein exposure for just a single month after the treatment leads to rapid and substantial decreases in tolerance, findings from a small study show.
The findings “underscore the fact that the desensitization achieved with peanut oral immunotherapy is a transient immune state,” report the authors of the study, published in December in The Journal of Allergy and Clinical Immunology: In Practice.
Therefore, “adherence to dosing [in peanut immunotherapy] is very important, and clinicians should expect a decline in tolerance with lapse in dosing,” first author Carla M. Davis, MD, director of the Texas Children’s Hospital Food Allergy Program at Baylor College of Medicine, in Houston, Texas, told Medscape Medical News.
Oral immunotherapy, involving small exposures to peanut protein to build up desensitization, has been shown to mitigate allergic reactions, and, as reported by Medscape Medical News, the first peanut oral immunotherapy drug recently received approval from the US Food and Drug Administration.
However, current approaches involve very low daily exposure of about 300 mg of peanut protein, equivalent to only about one to two peanuts, and research is lacking regarding the maximum tolerated doses as well as on how long the tolerance is sustained if maintenance therapy is discontinued. “For the peanut-allergic population that would like to eat more than 1-2 peanuts, an achievable dose is currently unknown,” the study authors write. “The critical question, of the maximum tolerated dose achieved after POIT, has not been answered.”
To evaluate those issues in their phase 2 study, Davis and her colleagues enrolled 28 subjects between the ages of 5 and 13 with a diagnosis of eosinophilic esophagitis and peanut allergy.
The treatment protocol included a 1-year buildup phase of oral immunotherapy, followed by a 2-year daily maintenance phase with a dose of 3900 mg of peanut protein.
After consenting, 11 patients dropped out of the study due to a lack of interest, and two more withdrew after failing to tolerate their first dose, leaving 15 who started treatment in the study, with a mean age of 8.7 years (range, 5.2 – 12.5 years), and 47% female.
Twelve patients reached the maintenance dose of 3900 mg over a median of 13 months, and double-blind, placebo-controlled peanut challenges showed that, on average, their mean maximum cumulative tolerated dose after 12 months increased by 12,063 mg (P < .001), and the mean dose triggering a reaction increased by 15,667 mg.
Of the 12 patients, 11 (91.7%) were able to successfully tolerate at least 10,725 mg after 12 months of treatment, and six patients (50.0%) successfully tolerated at least 15,225 mg.
Two patients were able to tolerate up to the maximum cumulative target dose of 26,225 mg, equivalent to more than 105 peanuts.
“The ability to tolerate [greater than] 100 peanuts following peanut oral immunotherapy has never before been demonstrated and gives insight into the potential for food oral immunotherapy to be utilized in a subset of patients who have an immunologic phenotype accepting of this therapy,” the authors write.
“Understanding the risk of ingestion of peanut protein higher than the prescribed peanut oral immunotherapy maintenance dose will improve the safe, practical use of [the therapy],” they add.
Tolerance Plummets With Avoidance
In the protocol’s third phase, after the 3-year buildup and maintenance therapy, daily peanut exposure was avoided for 30 days, and among the six patients who participated, the mean maximum cumulative tolerated dose declined to just 2783 mg, and the reaction dose dropped to 4614 mg (P = .03).
“This was a disappointing finding because we thought the desensitization would last longer after such a long period of treatment,” Davis said.
While the avoidance period was only a month, Davis said she expects the rebound in sensitivity would continue if avoidance was prolonged. “Other studies indicate the decline in tolerance would continue over time [and] we believe it would continue to decline,” she said.
Further analysis of peanut allergy biomarkers showed significant decreases in skin prick test wheal size and cytokine expression within the first 6 weeks of initiation of the peanut oral immunotherapy. The patterns were reversed during the 1-month avoidance, with both measures increasing.
Of note, the changes in biomarkers varied significantly among the participants.
In terms of adverse events, eight patients (53%) required one or two doses of epinephrine during the study, with all but two patients receiving the epinephrine during the 12 month buildup phase, consistent with previous studies.
In commenting on the study, Richard L. Wasserman, MD, PhD, medical director of pediatric allergy and immunology at Medical City Children’s Hospital, in Dallas, Texas, noted that the findings pertain to the subset of peanut oral immunotherapy patients (about 30%) who want to be able to eat peanuts.
“Most families just want protection against accidental ingestion, and these observations don’t relate to those patients,” he told Medscape Medical News.
Wasserman noted that his approach with patients is to wait until 3 years of daily maintenance after buildup (as opposed to 2 years in the study) before considering an avoidance challenge.
“When our patients pass a sustained unresponsiveness challenge, we recommend continued exposure of 2000 mg at least weekly,” he explained.
Wasserman added that the study’s findings on biomarker changes were notable.
“The eventual reduction in peanut serum IgE in all of their patients is very interesting,” he said. “Many of our patients’ peanut serum IgE plateaus after 2 or 3 years.”
And he added, “This report suggests that we should be making patients aware that they may further decrease their peanut serum IgE by increasing their maintenance dose.”
The study was funded by the Scurlock Foundation/Waring Family Foundation and the Texas Children’s Hospital food allergy program. Davis is a consultant for Aimmune, DBV, and Moonlight Therapeutics. Wasserman is a consultant for Aimmune and DBV.
J Allergy Clin Immunol Pract. Published December 7, 2021. Abstract
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