Dupilumab for treatment of food allergy

Rial, Manuel Jorge; Barroso, Blanca; Sastre, Joaquı́n

doi:10.1016/j.jaip.2018.07.027

Cited by 74 publications

(65 citation statements)

References 4 publications

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“…Abdel‐Gadir et al found that treatment of lymphocytes peanut‐allergic patients with anti‐IL‐4Rα mAb augmented the suppressive function of peanut‐reactive Treg cells, highlighting the potential disease‐modifying effect of anti‐IL4 therapy . Recently, Rial MJ et al have presented a case report showing a very successful therapy of newly developed food allergy to corn and nuts using Dupilumab . This is the first report treating a patient with Dupilumab for a food allergy indication.…”

Section: Dupilumab For Food Allergymentioning

confidence: 98%

Mechanisms of Dupilumab

Harb

Chatila

2019

Clin Experimental Allergy

318

241

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The Th2 cytokines interleukin 4 (IL‐4) and IL‐13 and the heterodimeric IL‐4 receptor (IL‐4R) complexes that they interact with play a key role in the pathogenesis of allergic disorders. Dupilumab is a humanized IgG4 monoclonal antibody that targets the IL‐4 receptor alpha chain (IL‐4Rα), common to both IL‐4R complexes: type 1 (IL‐4Rα/γc; IL‐4 specific) and type 2 (IL‐4Rα/IL‐13Rα1; IL‐4 and IL‐13 specific). In this review, we detail the current state of knowledge of the different signalling pathways coupled to the IL‐4R complexes and examine the possible mechanisms of Dupilumab action and survey its clinical efficacy in different allergic disorders. The development of Dupilumab and the widening spectrum of its clinical applications is relevant to the current emphasis on precision medicine approaches to the blockade of pathways involved in allergic diseases.

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Section: Dupilumab For Food Allergymentioning

confidence: 98%

Mechanisms of Dupilumab

Harb

Chatila

2019

Clin Experimental Allergy

318

241

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“…156 By suppressing IL-4 and IL-13, which are key for IgE class-switching, expansion, maintenance, and activation of effector cells, food-allergic responses may be abolished as suggested by recent case reports. 168,169 Rare, however significant side effects 170 and the not yet completely understood effects of IL-4 on innate immune function warrant further investigation. 171,172 Studies investigating the role of TSLP and IL-25 in the context of food allergy are limited, and recent data on the topic are still derived from rodent in vivo and in vitro models.…”

Section: Antig En -Uns Pecific and Additive A Pproache Smentioning

confidence: 99%

Recent developments and highlights in food allergy

Eiwegger

Hung

Diego

et al. 2019

Allergy

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The achievement of long-lasting, safe treatments for food allergy is dependent on the understanding of the immunological basis of food allergy. Accurate diagnosis is essential for management. In recent years, data from oral food challenges have revealed that routine allergy testing is poor at predicting clinical allergy for tree nuts, almonds in particular. More advanced antigen-based tests including component-resolved diagnostics and epitope reactivity may lead to more accurate diagnosis and selection of therapeutic intervention. Additional diagnostic accuracy may come from cellular tests such as the basophil activation test or mast cell approaches. In the context of clinical trials, cellular tests have revealed specific T-cell and B-cell populations that are more abundant in food-allergic individuals with distinct mechanistic features.Awareness of clinical markers, such as the ability to eat baked forms of milk and egg, continues to inform the understanding of natural tolerance development.Mouse models have allowed for investigation into multiple mechanisms of food allergy including modification of epithelial metabolism, and the induction of regulatory cell subsets and the microbiome. Increasing numbers of children who underwent food immunotherapy enlarged the body of evidence on mechanisms and predictors of treatment success. Experimental immunological markers in conjunction with clinical determinants such as lower age and lower initial specific IgE appear to be of benefit.More research on the optimal dose, preparation, and route of application integrating a high-level safety and efficacy is demanded. Alternatively, biologics blocking TSLP, IL-33, IL-4 and IL-13, or IgE may help to achieve that. K E Y W O R D Sallergy treatment, biologics, food allergy, immune tolerance, immunotherapy | 2357 EIWEGGER Et al.

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“…The patient was incidentally found to tolerate foods to which she was previously allergic and was originally diagnosed with corn allergy (anaphylactic shock and positive testing) and pistachio‐allergy (positive testing and positive oral food challenge). After starting dupilumab, the patient subsequently passed two oral challenges to corn and pistachio 79 . In a phase 2 trial of patients with active EoE, dupilumab reduced dysphagia, histologic features of disease (including eosinophilic infiltration and a marker of type 2 inflammation) and abnormal endoscopic features compared with placebo 80 …”

Section: Milestone Discoveriesmentioning

confidence: 99%