Evaluation of oral immunotherapy efficacy and safety by maintenance dose dependency: A multicenter randomized study

Naoyuki Kando,Sakura Sato,Masami Taniguchi,Ikuya Tsuge,Takanori Imai,Osamu Uchida,Rumiko Shibata,Norio Kawamoto,Kiyotake Ogura,Mizuho Nagao,Yoko Murakami,Noriyuki Yanagida,Takao Fujisawa,Kazuko Sugai,Komei Ito,Mitsuyoshi Urashima,Masanori Ikeda,Atsuo Urisu,Motohiro Ebisawa,Naomi Kondo,Yasuto Kondo

doi:10.1016/j.waojou.2020.100463

Abstract

BackgroundGenerally, oral immunotherapy (OIT) aims for daily administration. Recently, the efficacy of treatment with OIT at a low dose has been reported. However, the optimal dose and the evaluation of dose-dependent OIT outcome have not been described. MethodsA multicenter, parallel, open-labeled, prospective, non-placebo controlled, randomized study enrolled 101 Japanese patients for treatment with OIT. We hypothesized that target dose OIT would induce short-term unresponsiveness (StU) earlier than reduced dose OIT. StU was defined as no response to 6200 mg whole egg, 3400 mg milk, and 2600 mg wheat protein, as evaluated by oral food challenge after 2-week ingestion cessation. To compare the two doses of OIT efficacy, the maximum ingestion doses during the maintenance phase of OIT were divided into 100%-dose or 25%-dose groups against their target StU dose, respectively. A total of 51 patients were assigned to the 100%-dose group [hen's egg (HE) = 26, cow's milk (CM) = 13, wheat = 12] and 50 to the 25%-dose group (HE = 25, CM = 13, wheat = 12). Primary outcome was established by comparing StU at 1 year. Secondary outcome was StU at 2 years and established by comparing allergic symptoms and immunological changes. ResultsThe year 1 StU rates (%) for the 100%- and 25%-dose groups were 26.9 vs. 20.0 (HE), 7.7 vs. 15.4 (CM), and 50.0 vs. 16.7 (wheat), respectively. The year 2 StU rates were 30.8 vs. 36.0 (HE), 7.7 vs. 23.1 (CM), and 58.3 vs. 58.3 (wheat), respectively. There were no statistically significant differences in StU between years 1 and 2. The total allergic symptom rate in the 25%-dose group was lower than that in the 100%-dose group for egg, milk, and wheat. Antigen-specific IgE levels for egg-white, milk, and wheat decreased at 12 months. ConclusionsReduced maintenance dose of egg OIT showed similar therapeutic efficacy to the target dose. However, we were not able to clearly demonstrate the efficacy, particularly for milk and wheat. Reducing the maintenance dose for eggs, milk, and wheat may effectively lower the symptoms associated with their consumption compared to the target OIT dose. Furthermore, aggressive reduction of the maintenance dose might be important for milk and wheat, compared to the 25%-dose OIT. Trial registrationUMIN000009373, Multicenter Oral Immunotherapy for Hen's Egg, Cow's Milk, and Wheat-Allergic Children at Outpatient Clinic.

Highlights

Food allergy (FA) is a major health issue that has been increasing at the global level.[1]
Reducing the maintenance dose for eggs, milk, and wheat may effectively lower the symptoms associated with their consumption compared to the target oral immunotherapy (OIT) dose
Aggressive reduction of the maintenance dose might be important for milk and wheat, compared to the 25%-dose OIT

Summary

Introduction

Food allergy (FA) is a major health issue that has been increasing at the global level.[1]. Other studies[21,22,23] have reported that patients treated with OIT reached a state of desensitization or sustained unresponsiveness (SU) providing an overall improvement in their quality of life. These breakthrough findings suggest that the efficacy of OIT may be considered a beacon of hope for patients with severe FA. The optimal dose and the evaluation of dose-dependent OIT outcome have not been described

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