Biologics in eosinophilic esophagitis

Zhang, Simin; Assa’ad, Amal

doi:10.1097/aci.0000000000000741

Cited by 4 publications

(5 citation statements)

References 46 publications

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“…It is secreted by Th2 cells, mast cells, innate lymphoid cells of type 2 (ILC2s), and eosinophils, and by binding the α subunit of IL-5-R (CD125), it modulates eosinophilic activities from the proliferation of their progenitors to priming of cytotoxicity by mature cells and delaying their apoptosis [49]. As a consequence, the prolonged release of pro-fibrotic factors such as TGF-β1 and fibroblast growth factor 9 (FGF-9) is very strategic in all those processes underlying epithelial remodeling and esophageal dysmotility (i.e., basal zone hyperplasia, fibrosis of the lamina propria, and expansion of muscularis propria) [50]. A study conducted on the esophageal specimens of 312 patients highlighted a non-direct proportion between higher levels of IL-5 and both histological and endoscopic abnormalities.…”

Section: Mepolizumab Reslizumab and Benralizumabmentioning

confidence: 99%

The New Therapeutic Frontiers in the Treatment of Eosinophilic Esophagitis: Biological Drugs

Ridolo,

Barone,

Ottoni

et al. 2024

IJMS

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Eosinophilic esophagitis (EoE) is a multifaceted disease characterized by a wide heterogeneity of clinical manifestations, endoscopic and histopathologic patterns, and responsiveness to therapy. From the perspective of an effective approach to the patient, the different inflammatory mechanisms involved in the pathogenesis of EoE and biologics, in particular monoclonal antibodies (mAbs), targeting these pathways are needed. Currently, the most relevant is dupilumab, which interferes with both interleukin (IL)-4 and IL-13 pathways by binding IL-4 receptor α, and is the only mAb approved by the European Medicine Agency and US Food and Drug Administration for the treatment of EoE. Other mAbs investigated include mepolizumab, reslizumab, and benralizumab (interfering with IL-5 axis), cendakimab and dectrekumab (anti-IL-13s), tezepelumab (anti-TSLP), lirentelimab (anti-SIGLEG-8), and many others. Despite the undeniable economic impact of biologic therapies, in the near future, there will be room for further reflection about the opportunity to prescribe biologic agents, not only as a last-line therapy in selected cases such as patients with comorbidities involving common pathways. Although recent findings are very encouraging, the road to permanent success in the treatment of EoE is still long, and further studies are needed to determine the long-term effects of mAbs and to discover new potential targets.

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Section: Mepolizumab Reslizumab and Benralizumabmentioning

confidence: 99%

The New Therapeutic Frontiers in the Treatment of Eosinophilic Esophagitis: Biological Drugs

Ridolo,

Barone,

Ottoni

et al. 2024

IJMS

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“…Eosinophilic esophagitis is an antigen-driven non-IgE-mediated disease, sustained by a type 2 inflammation, and defined by the presence of at least 15 eosinophils per high power field (HPF) on esophageal biopsies [ 91 ]. This condition is responsible for different clinical patterns, with a prevalence of dysphagia, food impaction, and chest pain in adults, and non-specific symptoms commonly present in children, such as vomiting, feeding difficulties, and failure to thrive [ 92 ].…”

Section: Eosionophilic Esophagitismentioning

confidence: 99%

“…As a result of eosinophil and mast cell activation, the prolonged release of pro-fibrotic factors (i.e., transforming growth factor-β1, FGF-9) enhances the epithelial remodeling, resulting in basal zone hyperplasia, lamina propria fibrosis. and expansion of muscularis propria, thus leading to esophageal dysmotility and strictures [ 91 ]. In addition, a study performed on a multi-site cohort of more than 300 patients from 4 to 71 years of age, highlighted a higher expression of IL-5 in active cases of EoE (defined by histopathologic and endoscopic findings, and molecular profiling).…”

Section: Eosionophilic Esophagitismentioning

confidence: 99%

Anti-IL-5 Pathway Agents in Eosinophilic-Associated Disorders Across the Lifespan

Lombardi,

Comberiati,

Ridolo

et al. 2024

Drugs

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Monoclonal antibodies targeting interleukin (IL)-5 pathways have revolutionized the treatment expectations for eosinophilic-associated conditions, particularly in patients with respiratory involvement. Mepolizumab (IL-5 antagonist monoclonal antibody), benralizumab (IL-5 receptor blocker monoclonal antibody), and reslizumab (IL-5 antagonist monoclonal antibody) have collectively contributed to the overall improvement of the disease burden in various conditions. Eosinophilic asthma currently boasts the most robust evidence across all age groups: all three biologics are approved for adults (aged ≥18 years); mepolizumab is approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) also in children (aged ≥ 6 years), while bernalizumab was recently approved by the FDA for patients aged ≥6 years in the USA. In chronic rhinosinusitis with nasal polyps, subcutaneous mepolizumab is the only anti-IL-5 therapy approved so far and can be used in adult patients (aged ≥18 years). For eosinophilic esophagitis, conflicting evidence surrounds both mepolizumab, reslizumab, and benralizumab, leading to non-approval of these agents by the FDA/EMA. Recently, mepolizumab was approved for eosinophilic granulomatosis with polyangiitis patients aged ≥6 years or older and for hypereosinophilic syndrome adult patients. A phase III trial proving noninferiority of benralizumab versus mepolizumab in eosinophilic granulomatosis with polyangiitis has been recently published, while evidence on reslizumab is scant. Overall, current evidence on anti-IL-5 biologics for eosinophilic-associated disorders is mostly focused on adults, whereas data for individuals aged under 18 years and over 65 years are scarce, resulting in a lack of evidence, particularly regarding efficacy, for the use of anti-IL-5 agents in these specific patient populations. This review addresses high-quality evidence from randomized controlled trials and real-world post-marketing studies regarding the use of anti-IL-5 therapies for eosinophilic-associated disorders across all age groups, spanning childhood, adulthood, and older age.

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“… 113 Biologics with anti-IL-5 activity are also under investigation including benralizumab, mepolizumab, and reslizumab. 115 Anti-IL-13 targeted biologics studied in adult EoE patients has demonstrated significant decrease in cellular markers of epithelial mesenchymal transition which mediates the complication of fibrostenosis in patients. 116–118 Hirano et al’s study of a monoclonal antibody against IL-13 showed a dose-dependent reduction in mean esophageal eosinophil count per hpf at 16 weeks of 94.8 ± 67.3 compared to placebo.…”

Section: Eosinophilic Gastrointestinal Disorders (Egids)mentioning

confidence: 99%

Pathophysiology of Non-IgE-Mediated Food Allergy

Zhang¹,

Sicherer²,

Berin³

et al. 2021

ITT

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Non-IgE-mediated food allergies are a group of disorders characterized by subacute or chronic inflammatory processes in the gut. Unlike IgE mediated food allergies that may result in multi-organ system anaphylaxis, the non-IgE mediated food allergies primarily affect the gastrointestinal tract. This review outlines the clinical manifestations, epidemiology, pathophysiology, and management of non-IgE-mediated food allergies. An updated literature search of selected non-IgE-mediated food allergies was conducted for this review using PubMed database to the current year (2021). Reviewed disorders include food protein-induced enterocolitis syndrome (FPIES), food-protein enteropathy (FPE), food protein-induced allergic proctocolitis (FPIAP), and eosinophilic gastrointestinal disorders (EGIDs) such as eosinophilic esophagitis (EoE). While extensive gains have been made in understanding FPIES, FPIAP, FPE, and EoE, more information is needed on the pathophysiology of these food allergies. Similarities among them include involvement of innate immunity, T-lymphocyte processes, alteration of the intestinal lumen at the cellular level with the appearance of inflammatory cells and associated histologic changes, and specific cytokine profiles suggesting food-specific, T-cell, and immune-mediated responses. While FPIES and FPIAP typically resolve in early childhood, EGIDs typically do not. Emerging new therapies for EoE offer promise of additional treatment options. Further studies identifying the immunopathogenesis, associated biomarkers, and mechanisms of tolerance are needed to inform prevention, diagnosis and management.

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Biologics in eosinophilic esophagitis

Cited by 4 publications

References 46 publications

The New Therapeutic Frontiers in the Treatment of Eosinophilic Esophagitis: Biological Drugs

The New Therapeutic Frontiers in the Treatment of Eosinophilic Esophagitis: Biological Drugs

Anti-IL-5 Pathway Agents in Eosinophilic-Associated Disorders Across the Lifespan

Pathophysiology of Non-IgE-Mediated Food Allergy

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