Peanut Gastrointestinal Delivery Oral Immunotherapy in Adolescents: Results of the Build–up Phase of a Randomized, Double–Blind, Placebo-Controlled Trial (PITA Study)

Abstract

To assess the efficacy and safety using a new approach to oral immunotherapy in which high-risk peanut-allergic adolescents ingested sealed capsules of incrementally increasing amounts of peanut protein. In most published studies, peanut is administered in a vehicle food. The authors hypothesized that bypassing the upper digestive tract could improve efficacy because the lower digestive tract, the main anatomic site of oral tolerance, would be targeted, and sealed capsules would circumvent taste aversion.Adolescents with peanut allergy were recruited for the study. Inclusion criteria included having a clinical reaction within 60 minutes after ingestion of peanut and demonstration of sensitization either by skin prick test (wheal >3 mm) or serum immunoglobulin E >12 IU/mL for peanut or >5.8 IU/mL for Ara h2 peanut component. Exclusion criteria included a teenager’s history of severe anaphylaxis requiring ICU support; severe persistent asthma; poorly controlled atopic dermatitis; concomitant severe food allergy to egg, milk, nuts, or sunflower seed; and/or inability to manage a severe allergic reaction. All patients underwent an initial double-blind, placebo-controlled food challenge (DBPCFC) with sealed capsules containing peanut protein; to be included in the study, the adolescent had to have a convincing objective reaction occurring after a cumulate intake of >20 and ≤400 mg of peanut protein.Patients were randomly assigned 2:1 to active treatment (peanut) or placebo (sunflower). Patients ingested a daily treatment dose of peanut protein or placebo via sealed gelatin capsules starting at 2 mg; doses were incrementally increased every 2 weeks up to 400 mg over a 24-week period. A second DBPCFC was performed at the end of the build-up phase. Cumulative ingestion of >400 mg of peanut protein without symptoms was the definition of desensitization.Fifty-one patients were screened, 21 patients were excluded because they tolerated 400 mg of peanut protein at the initial DBPCFC, and 30 patients were enrolled because they had a positive initial DBPCFC. Of these 30 enrolled patients, 21 were allocated to the peanut group and 9 were allocated to the placebo group. Two patients assigned to the peanut group withdrew from the study because of side effects; 1 of these patients experienced a severe adverse event (AE) but had inadvertently ingested twice the investigated amount. An additional 2 patients in the peanut group were unable to increase their intake threshold >400 mg but did increase their threshold level six- and sevenfold, respectively. Unresponsiveness to >400 mg of peanut protein was achieved in 17 of 21 (81%) patients with peanut allergy. Only 1 of 9 patients in the placebo group achieved this level of unresponsiveness. The number of patients experiencing AEs was not different between the 2 groups, but in the treated group, the number of AEs per patient was higher and AEs were more severe. Digestive AEs were more frequent in the treated group (P = .02). Oropharyngeal symptoms were equally frequent in both groups; no dysphagia or signs of eosinophilic esophagitis were noted.The PITA trial demonstrated an effective and safe way to induce peanut desensitization in high-risk adolescents with peanut allergy by using sealed capsules of peanut protein.Parents ask me every day when they can start their child on oral immunotherapy; they are worried if they wait too long that they will miss the window of opportunity for their child to overcome their food allergy. This study is promising because the researchers specifically targeted high-risk adolescents with peanut allergy, demonstrating that even older children and teenagers can successfully be desensitized. Food aversion (taste and smell) is a significant issue for many patients with food allergy; using the sealed capsules made this a moot point. Additional studies are warranted to further explore the safety and efficacy of this approach in larger groups of patients.