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

Background Generally, 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. Methods A 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. Results The 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. Conclusions Reduced 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

Usefulness of antigen-specific IgE probability curves derived from the 3gAllergy assay in diagnosing egg, cow's milk, and wheat allergies

Background: Specific IgE (sIgE) antibody detection using the Siemens IMMULITE® 3gAllergy™ (3gAllergy) assay have not been sufficiently examined for the diagnosis of food allergy. The aim of this study was to evaluate the utility of measuring sIgE levels using the 3gAllergy assay to diagnose allergic reactions to egg, milk, and wheat. Methods: This retrospective study was conducted on patients with diagnosed or suspected allergies to egg, milk and wheat. Patients were divided into two groups according to their clinical reactivity to these allergens based on oral food challenge outcomes and/or convincing histories of immediate reaction to causative food(s). The sIgE levels were measured using 3gAllergy and ImmunoCAP. Predicted probability curves were estimated using logistic regression analysis. Results: We analyzed 1561 patients, ages 0–19 y (egg = 436, milk = 499, wheat = 626). The sIgE levels determined using 3gAllergy correlated with those of ImmunoCAP, classifying 355 patients as symptomatic: egg = 149, milk = 123, wheat = 83. 3gAllergy sIgE levels were significantly higher in symptomatic than in asymptomatic patients (P < 0.0001). Predictive probability for positive food allergy was significantly increased and correlated with increased sIgE levels. The cut-offs for allergic reaction with 95% predictive probability as determined by the 3gAllergy probability curves were different from those of ImmunoCAP. Conclusions: Measurements of sIgE against egg, milk, and wheat as determined by 3gAllergy may be used as a tool to facilitate the diagnosis of food allergy in subjects with suspected food allergies. However, these probability curves should not be applied interchangeably between different assays

Skin prick test is more useful than specific IgE for diagnosis of buckwheat allergy: A retrospective cross-sectional study

Background: Buckwheat (BW) is a potentially life-threatening allergen. Usefulness of BW-specific immunoglobulin-E (BW-sIgE) level for diagnosis of BW allergy is controversial, while the skin prick test (SPT) is widely used because of its less invasive procedure and immediate results. However, there are no data comparing usefulness of the SPT and BW-sIgE level. Therefore, our study aimed to clarify efficacy of the SPT for diagnosis of BW allergy. Methods: This retrospective cross-sectional study evaluated patients who underwent an oral food challenge (OFC) for diagnosis or confirmation of acquired tolerance using 3072 mg of BW protein between July 2006 and April 2014. We then compared the diagnostic performance of BW sIgE and SPT to predict positive OFC results. Results: We analyzed 126 patients aged 2–16 years (median, 7.7 years), 18 (14%) of whom showed positive OFC results. Between patients with positive and negative OFC results, there was no significant difference in BW-sIgE level. However, patients with positive OFC results had a larger SPT wheal diameter. Area under the curve for positive OFC results for BW-sIgE level and SPT wheal diameter were 0.583 and 0.791, respectively. The 5%, 10%, 50%, and 90% positive predictive values of SPT wheal diameter were 2.0 mm, 5.2 mm, 14.7 mm, and 24.1 mm, respectively. Conclusions: Our study revealed that the SPT was more useful than BW-sIgE level for diagnosis of BW allergy. Thus, an OFC may be avoided if the patient's SPT wheal diameter is at least 24.1 mm

Specific IgE for Fag e 3 Predicts Oral Buckwheat Food Challenge Test Results and Anaphylaxis: A Pilot Study

Background: Buckwheat (BW) is the source of a life-threatening allergen. Fag e 3-specific serum IgE (sIgE) is more useful than BW-sIgE for diagnosis; however, it is unknown whether Fag e 3-sIgE can predict oral food challenge (OFC) results and anaphylaxis. This study aimed to clarify the efficacy of Fag e 3-sIgE in predicting OFC results and anaphylaxis. Methods: We conducted a retrospective review of BW- and Fag e 3-sIgE data obtained using the ImmunoCAP® assay system and fluorescent enzyme-linked immunosorbent assay from children who underwent OFC using 3, 072 mg of BW protein between July 2006 and March 2014 at Sagamihara National Hospital, Kanagawa, Japan. Results: We analyzed 60 patients aged 1.9–13.4 years (median 6.0 years); 20 (33%) showed objective symptoms upon BW OFC. The patients without symptoms had significantly lower Fag e 3-sIgE than those with non-anaphylactic (p < 0.001) and anaphylactic reactions to BW (p = 0.004). Fag e 3-sIgE was the only tested factor that significantly predicted positive OFC results (odds ratio 8.93, 95% confidence interval 3.10–25.73, p < 0.001) and OFC-induced anaphylaxis (2.67, 1.12–6.35, p = 0.027). We suggest that a threshold Fag e 3-sIgE level of 18.0 kUE/L has 95% probability of provoking a positive reaction to BW. Conclusions: Fag e 3-sIgE predicted OFC results and OFC-induced anaphylaxis. We further emphasize paying careful attention to the risk of BW OFC-induced anaphylaxis