Original Article
Efficacy, Safety, and Quality of Life in a Multicenter, Randomized, Placebo-Controlled Trial of Low-Dose Peanut Oral Immunotherapy in Children with Peanut Allergy

https://doi.org/10.1016/j.jaip.2018.10.048Get rights and content

Background

Only 2 small placebo-controlled trials on peanut oral immunotherapy (OIT) have been published.

Objective

We examined the efficacy, safety, immunologic parameters, quality of life (QOL), and burden of treatment (BOT) of low-dose peanut OIT in a multicenter, double-blind, randomized placebo-controlled trial.

Methods

A total of 62 children aged 3 to 17 years with IgE-mediated, challenge-proven peanut allergy were randomized (1:1) to receive peanut OIT with a maintenance dose of 125 to 250 mg peanut protein or placebo. The primary outcome was the proportion of children tolerating 300 mg or more peanut protein at oral food challenge (OFC) after 16 months of OIT. We measured the occurrence of adverse events (AEs), immunologic changes, and QOL before and after OIT and BOT during OIT.

Results

Twenty-three of 31 (74.2%) children of the active group tolerated at least 300 mg peanut protein at final OFC compared with 5 of 31 (16.1%) in the placebo group (P < .001). Thirteen of 31 (41.9%) children of the active versus 1 of 31 (3.2%) of the placebo group tolerated the highest dose of 4.5 g peanut protein at final OFC (P < .001). There was no significant difference between the groups in the occurrence of AE-related dropouts or in the number, severity, and treatment of objective AEs. In the peanut-OIT group, we noted a significant reduction in peanut-specific IL-4, IL-5, IL-10, and IL-2 production by PBMCs compared with the placebo group, as well as a significant increase in peanut-specific IgG4 levels and a significant improvement in QOL; 86% of children evaluated the BOT positively.

Discussion

Low-dose OIT is a promising, effective, and safe treatment option for peanut-allergic children, leading to improvement in QOL, a low BOT, and immunologic changes showing tolerance development.

Introduction

Peanut allergy is a common disease in childhood, with estimated prevalence rates ranging from 0.4% in Europe1 to 3% in Australia.2 Ingestion of only small quantities of the allergen may lead to potentially life-threatening allergic reactions.3 Thus, peanut is the most common allergen to induce food-induced anaphylaxis in childhood.4 Patients are advised to strictly avoid peanut, but accidental reactions are common due to the widespread use of peanut in the food industry.5 Thus, patients are also advised to carry self-administered epinephrine at all times. Overall, quality of life (QOL) in patients with peanut allergy is reduced.6, 7 Therefore, there is a need for an allergen-specific therapy in this group of patients.

Recent research has focused on the therapeutic option of oral allergen-specific immunotherapy. Published trials on peanut oral immunotherapy (OIT) have demonstrated clinical desensitization of most of the patients, although different doses for maintenance were used.8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 However, all trials were small and only 2 were placebo-controlled. Mild to moderate adverse reactions were reported in most patients. Some patients even suffered from anaphylactic reactions associated with OIT dosing. Although OIT seems an effective treatment option for patients with peanut allergy, safety has to be evaluated more carefully.

Hypothetically, using a low maintenance dose and a long updosing period in peanut OIT might lead to the same efficacy but better safety profile than using a higher maintenance dose for a shorter updosing period. The aim of this double-blind, placebo-controlled study was to assess efficacy for clinical desensitization and safety of OIT as well as possible changes in immunologic parameters, QOL after OIT, and the burden of treatment (BOT) in children with peanut allergy using the lowest maintenance dose so far reported. It is one of the first placebo-controlled peanut-OIT trials where oral food challenges (OFCs) were conducted before and after OIT, where a high enough top dose of peanut protein was included into the final OFC to define a proper threshold after OIT in individual patients, where safety was assessed thoroughly, and the first where changes in QOL and BOT were investigated in a placebo-controlled way.

Section snippets

Study overview

This investigator-initiated, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial was conducted at 7 German sites (see this article's Study centers section in the Online Repository at www.jaci-inpractice.org). We recruited patients consecutively in the outpatient clinics or from a list of peanut-sensitized children followed within these tertiary care clinics. The study protocol and consent forms were approved by all ethics committees. All caregivers of the study

Study population

Of 186 children with suspected peanut allergy approached for the study, 119 refused to participate, 4 were tolerant to peanut at the initial OFC, and the youngest patient vigorously refused to eat the vehicle (chocolate pudding) (see Figure 1, Consolidated Standards of Reporting Trials flow diagram). Thus, 62 participants with a median age of 6.8 years (range, 3.2-17.8 years), median peanut-specific IgE of 81.5 kU/L (range, 0.57-624 kU/L), median Ara h 2–specific IgE of 44.7 kU/L (range,

Efficacy

This study is the first study to target highly sensitive patients with peanut allergy with a low-dose peanut OIT in a randomized, placebo-controlled fashion showing a good efficacy for clinical desensitization, an excellent safety profile, a prevention of accidental reactions, immunomodulatory capacity, improvement in HRQOL, and a low BOT. Efficacy was highly significant, with 74% of the active group meeting the primary end point in tolerating a dose of at least 300 mg peanut protein at final

Acknowledgments

We thank Clare Mills, formerly from the Institute of Food Research, Norwich, United Kingdom, for providing the recipe for the chocolate peanut pudding; Stefan Boguslawski from the Institute for Food Technology and Chemistry of the Technical University Berlin for helping to establish the chocolate peanut pudding in Berlin; and Nadine Guzy for helping to prepare the pudding. We are grateful to Kornelia Kleiner, Paul-Ehrlich Institute, for excellent technical assistance in peanut protein

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  • Cited by (0)

    This investigator-initiated study was sponsored by a grant from the Charité Universitätsmedizin Berlin, the “Foundation for the treatment of peanut-allergic patients (bea Stiftung),” and “The Berlin Sparkasse Foundation for Medicine.” SGS Institute Fresenius, Germany, assessed the oral immunotherapy vehicle (chocolate peanut/placebo pudding) for microbial contamination free of charge.

    Conflicts of interest: K. Blumchen reports personal fees and nonfinancial support from Novartis; personal fees from HAL Allergy, ThermoFisher, and Bencard Allergie; and grants and personal fees from Aimmune Therapeutics outside the submitted work. T. Holzhauser reports personal fees and nonfinancial support from Akademie Fresenius; and nonfinancial support from the European Academy of Allergology and Clinical Immunology, Deutscher Allergie- und Asthmabund eV, and Deutsche Gesellschaft für experimentelle und klinische Pharmakologie und Toxikologie eV; German Research Foundation; German Federal Office of Consumer Protection and Food Safety; and EU-COST Action ImpARAS outside the submitted work. K. Beyer reports grants and personal fees from Aimmune Therapeutics; grants from DBV; and personal fees from Mabylon AG outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest.

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