Oral Immunotherapy in Peanut-Allergic Adults Using Real-World Materials

Abstract

Background: Peanut oral immunotherapy (OIT) has shown effectiveness in achieving desensitization of children; however, evidence in adults is lacking. Methods: This phase II trial evaluated peanut OIT in peanut-allergic adults using real-world peanut products. A Simon's minimax two-stage design, incorporating a stop:go for futility, was employed. A separate untreated control group was also recruited for comparison of mechanistic parameters. Participants underwent baseline double-blind placebo-control food challenges (DBPCFC) with peanut protein doses of 0.3 to 300 mg. Reacting participants were initiated on daily OIT with 2-weekly updosing until reaching a maintenance dose of 1000 mg (four large peanuts). The primary outcome was the proportion of OIT participants who tolerated a cumulative dose of 1.4 g peanut protein during exit DBPCFC (doses provided 0.3-3000 mg). Results: Twenty-one adults (8 female; mean age 24.2 years [SD 4.9]) were enrolled in the OIT group, with 67% achieving the daily maintenance dose and meeting the primary endpoint. Three withdrew due to adverse reactions, and a further three did not complete the trial for reasons unrelated to OIT. The median tolerated dose increased from 30 mg (equivalent to approximately 1/8th of a peanut) to 3000 mg (12 peanuts) at the exit challenge, representing a 100-fold increase (p < 0.0001). OIT was associated with an improvement in QoL measures. Suppression of peanut skin prick test sizes and induction of peanut-specific IgG were observed in OIT but not in control participants. Conclusions: Peanut OIT appears to be an efficacious treatment for adults with peanut allergy. Further studies are needed for confirmation and to characterize safety profiles in different adult subgroups. Trial Registration: Grown Up Peanut Immunotherapy (GUPI) study; ClinicalTrials.gov identifier: NCT03648320.