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 2,783 mg, and the reaction dose dropped to 4,614 mg (P = .03).
“This was a disappointing finding, because we thought the desensitization would last longer after such a long period of treatment,” Dr. Davis said.
While the avoidance period was only a month, Dr. 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, Dallas, 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 said in an interview.
Dr. 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 2,000 mg at least weekly,” he explained.
Dr. 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. Dr. Davis is a consultant for Aimmune, DBV, and Moonlight Therapeutics. Dr. Wasserman is a consultant for Aimmune and DBV.
A version of this article first appeared on Medscape.com.