Abatacept to induce remission of peanut allergy during oral immunotherapy (ATARI): protocol for a phase 2a randomized controlled trial.

Context: While oral immunotherapy (OIT) has been shown to promote the remission of mild peanut allergy in young children, there is still an unmet need for a disease-modifying intervention for older patients and those with severe diseases. In mice models, abatacept, a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) immunoglobulin fusion protein, has been shown to promote immune tolerance to food when used as an adjuvant to allergen immunotherapy. The goal of this study is to explore the potential efficacy of abatacept in promoting immune tolerance to food allergens during OIT in humans. Methods: In this phase 2a proof-of-concept study (NCT04872218), 14 peanut-allergic participants aged from 14 to 55 years will be randomized at a 1:1 ratio to abatacept vs. placebo for the first 24 weeks of a peanut OIT treatment (target maintenance dose of 300 mg peanut protein). The primary outcome will be the suppression of the OIT-induced surge in peanut-specific IgE/total IgE at 24 weeks, relative to the baseline. Sustained unresponsiveness will be assessed as a secondary outcome starting at 36 weeks by observing incremental periods of peanut avoidance followed by oral food challenges. Discussion: This is the first study assessing the use of abatacept as an adjuvant to allergen immunotherapy in humans. As observed in preclinical studies, the ability of abatacept to modulate the peanut-specific immune response during OIT will serve as a proxy outcome for the development of clinical tolerance, given the small sample size. The study will also test a new patient-oriented approach to sustained tolerance testing in randomized controlled trials.

Pilot Study of the Applicability, Usability, and Accuracy of the Nutricate© Online Application, a New Dietary Intake Assessment Tool for Managing Infant Cow's Milk Allergy.

BACKGROUND/OBJECTIVES: The mainstay treatment of cow's milk allergy (CMA) is to remove cow's milk proteins from children's dietary intake. In this context, dietary intake of children with CMA should be particularly checked and monitored. The objective of this study was to assess the applicability, usability, and accuracy of a new dietary intake (DI) assessment online tool (Nutricate© online application) for managing CMA in children. SUBJECTS/METHODS: This study used a pre-existing database of DI from the Nutricate© online application. DIs from 30 CMA children were used to compare micro/macronutrients (energy, protein, calcium, and iron intakes) calculated by Nutricate© and NutriLog© as the reference method. Comparisons were performed using the Pearson correlation analysis and the Bland-Altman plot. The Nutricate© tool usability was assessed via a System Usability Scale questionnaire (SUSq). RESULTS: Correlation coefficient between the levels of micro/macronutrients obtained by Nutrilog© and Nutricate© software were highly significant (p = 0.0001) and were well-correlated (R coefficient > 0.6), indicating a very good concordance between the two methods. This observation was reinforced by the Bland-Altman plot, indicating the absence of proportional or fixed bias for energy, protein, calcium, and iron intakes. The mean SUSq score obtained was 81 ± 14, which is considered to be an excellent score. CONCLUSIONS: Nutricate© online application is a reliable method to assess micro/macronutrient (energy, protein, calcium, and iron intakes) intake in CMA children. Applicability and usability of this new dietary intake assessment online tool is excellent.

Economic considerations on the usage of biologics in the allergy clinic.

The advent of biologic therapies has transformed care for severe atopic disorders but their high cost poses new challenges with regard to long-term sustainability and fair allocation of resources. This article covers the basic concepts of cost-utility analyses and reviews the available literature on cost utility of biologic drugs in atopic disorders. When used within their limits as part of a multi-dimensional assessment, economic analyses can be extremely useful to guide decision-making and prioritization of care. Despite the good quality of most cost-utility analyses conducted for the use of biologics in asthma and other atopic diseases, their conclusions regarding cost-effectiveness are extremely variable. This is mainly due to the use of inconsistent estimates of health utility benefit with therapy. Development of reliable and validated instruments to measure disutility in atopic disorders and measure of indirect costs in atopic disease are identified as a priority for future research.

Determinants of omalizumab dose-related efficacy in oral immunotherapy: Evidence from a cohort of 181 patients.

BACKGROUND: Omalizumab has been shown to improve the safety and feasibility of oral immunotherapy (OIT), but the optimal dosage strategy is unknown. OBJECTIVE: Our aim was to identify determinants of omalizumab dose-related efficacy in the context of OIT. METHODS: The study sample consisted of a clinical cohort of 181 patients treated with omalizumab-enabled oral immunotherapy at 3 centers. Patients received omalizumab for at least 2 months before an initial food escalation (IFE) with a mix of up to 6 allergens. Progression through IFE steps was assessed with survival analysis. Continued food dose tolerance with omalizumab weaning was also documented. RESULTS: Omalizumab dosage per weight alone was strongly associated with progression through the IFE (χ2 = 28.18; P < .0001), whereas the standard dosage per weight and total IgE level used for asthma was not (χ2 = 0.001; P = .97). When the values at time of IFE were estimated through pharmacokinetics and pharmacodynamics simulation, IFE outcome was best predicted by a model that includes levels of free allergen-specific IgE and their interaction with blocking omalizumab-IgE complexes and free omalizumab levels in serum (χ2 = 65.84; degrees of freedom [df] = 2; P < .0005). The occurrence of immediate-type reactions to food dosing subsequent to weaning of omalizumab was associated with a greater ratio of specific IgE level to total IgE level at baseline (geometric mean 0.39 vs 0.16 in those without symptom; P < .0001). CONCLUSION: In the context of OIT and IgE-mediated disease, omalizumab dosages should be adjusted for body weight alone, independently of total IgE level. The fraction of allergen-specific/total IgE may be useful to predict patients at greater risk of food dosing reactions subsequent to weaning.

Correction to: Protocol for a double-blind, randomized controlled trial on the dose-related efficacy of omalizumab in multi-food oral immunotherapy.

[This corrects the article DOI: 10.1186/s13223-020-00419-z.].

Children with eosinophilic esophagitis in real life: 10 years' experience with a focus on allergic management

INTRODUCTION AND OBJECTIVES: Eosinophilic esophagitis (EoE) is frequently miss-diagnosed or overlooked for several years because of the invasiveness of investigations and the non-specificity of symptoms in childhood. Due to the lack of specific recommendations in children, its management remains very heterogeneous, especially concerning allergy testing. The aim of this study is to analyze our population and practices, in comparison with the literature, with a focus on allergic management, to harmonize and optimize our practice. MATERIAL AND METHODS: We included all children with a diagnosis of EoE at the Hospital Femme Mere Enfant, Bron, France. Data were collected via retrospective chart review. RESULTS: 108 patients were included with an average age of 9.5 years. Average delay before diagnosis was 6.65 years. Symptoms varied with age, with a predominance of vomiting (60% of patients), feeding difficulties (72%) and growth difficulties (24%) in children < 5 years, whereas older children often presented with feeding blockage (64%) and dysphagia (61%). Cough was frequent in our cohort (18.5%), especially in children < 10 years (38.5% between three and five years). The allergic background was frequent (70.3%) and 80% of our patients benefited from allergy testing. Allergy testing was particularly useful to guide therapy as elimination diet represented an effective treatment in 60% of our patients CONCLUSIONS: Allergy testing has to be harmonized to include major allergens (egg, milk, peanut, fish, wheat, and soy), including prick and patch tests. Allergy-testing based diet seemed to be the best compromise between efficiency and constraints, especially in mono-sensitized patients

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Protocol for a double-blind, randomized controlled trial on the dose-related efficacy of omalizumab in multi-food oral immunotherapy.

BACKGROUND: Previous proof-of-concept studies have shown that a short course of omalizumab can safely accelerate the oral immunotherapy schedule for multiple allergens simultaneously. Considering the high cost of medication, the dose-related efficacy of omalizumab at decreasing the duration of oral immunotherapy up-dosing phase must be objectively quantified before cost-benefit analyses can be performed. The primary objective of this trial will be to compare the efficacy of 2 omalizumab dosages to placebo at decreasing time-to-maintenance dose during a symptom-driven multi-food OIT protocol. METHODS: A total of 90 participants aged 6 to 25 with multiple food allergies (3 or more) will be enrolled at four sites in Canada. Participants will be randomized to: (A) Omalizumab 8 mg/kg per month (n = 36); (B) Omalizumab 16 mg/kg per month (n = 36); or (C) Placebo (n = 18). Study drug will be administered at full dosage for 12 weeks, then progressively tapered at 50% dosage (8 mg/kg vs 4 mg/kg vs placebo) for 4 weeks and at 25% dosage (4 mg/kg vs 2 mg/kg vs placebo) for another 4 weeks. After a pre-treatment period of 8 weeks, participants will undergo an initial food escalation (IFE) to an OIT mix containing 3 allergens and start daily home dosing with biweekly increases until a target daily maintenance of 1500 mg protein is achieved. The amount escalated at each visit will vary based on treatment tolerance according to a standardized up-dosing algorithm. Participants will be followed for at least 12 months following the initial food escalation. The primary endpoint will be time from IFE to the target maintenance dose of 1500 mg protein. Time-to-event analytic methods, including the log-rank test, will be used to compare the 3 arms. DISCUSSION: This trial uses a novel pragmatic approach to compare OIT with omalizumab to OIT without omalizumab in a blinded manner, which allows to single out the effect of this anti-IgE medication on treatment effectiveness speed without the recourse to predetermined schedules. The innovative patient-centered up-dosing algorithm allows to maximise treatment effectiveness speed without compromising patient safety, regardless of whether the patient is on omalizumab or not. This study will also provide novel prospective data to inform on the optimal and most cost-effective dosage for this indication.Trial registration ClinicalTrials.gov, NCT04045301, Registered 5 August 2019, https://clinicaltrials.gov/ct2/show/NCT04045301.

Children with eosinophilic esophagitis in real life: 10 years' experience with a focus on allergic management.

INTRODUCTION AND OBJECTIVES: Eosinophilic esophagitis (EoE) is frequently miss-diagnosed or overlooked for several years because of the invasiveness of investigations and the non-specificity of symptoms in childhood. Due to the lack of specific recommendations in children, its management remains very heterogeneous, especially concerning allergy testing. The aim of this study is to analyze our population and practices, in comparison with the literature, with a focus on allergic management, to harmonize and optimize our practice. MATERIAL AND METHODS: We included all children with a diagnosis of EoE at the Hospital Femme Mere Enfant, Bron, France. Data were collected via retrospective chart review. RESULTS: 108 patients were included with an average age of 9.5 years. Average delay before diagnosis was 6.65 years. Symptoms varied with age, with a predominance of vomiting (60% of patients), feeding difficulties (72%) and growth difficulties (24%) in children <5 years, whereas older children often presented with feeding blockage (64%) and dysphagia (61%). Cough was frequent in our cohort (18.5%), especially in children <10 years (38.5% between three and five years). The allergic background was frequent (70.3%) and 80% of our patients benefited from allergy testing. Allergy testing was particularly useful to guide therapy as elimination diet represented an effective treatment in 60% of our patients CONCLUSIONS: Allergy testing has to be harmonized to include major allergens (egg, milk, peanut, fish, wheat, and soy), including prick and patch tests. Allergy-testing based diet seemed to be the best compromise between efficiency and constraints, especially in mono-sensitized patients.