Emerging drugs for eosinophilic esophagitis

Kern, Emily; Hirano, Ikuo

doi:10.1517/14728214.2013.829039

Cited by 9 publications

(9 citation statements)

References 64 publications

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“…While corticosteroids are a frontline therapy for EoE children and adults, there is a subset of EoE patients who are steroid refractory [64–66]. In addition, given its chronic nature, EoE seems to require long-term topical corticosteroids or dietary management.…”

Section: Effectiveness Of Available Therapies For Remodeling In Eoementioning

confidence: 99%

Clinical Implications and Pathogenesis of Esophageal Remodeling in Eosinophilic Esophagitis

Hirano

Aceves

2014

Gastroenterology Clinics of North America

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115

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In eosinophilic esophagitis (EoE), remodeling changes are manifest histologically in both the epithelium as well as in the subepithelium where lamina propria (LP) fibrosis, expansion of the muscularis propria and increased vascularity occur. The major clinical symptoms and complications of EoE are largely consequences of esophageal remodeling. Important mediators of the process include IL-5, IL-13, TGFβ1, mast cells, fibroblasts and eosinophils. Methods to detect remodeling effects include upper endoscopy, histopathology, barium esophagram, endoscopic ultrasonography, esophageal manometry, and functional luminal imaging. These modalities provide evidence of organ dysfunction that include focal and diffuse esophageal strictures, expansion of the mucosa and subepithelium, esophageal motor abnormalities and reduced esophageal distensibility. Complications of food impaction and perforations of the esophageal wall have been associated with reduction in esophageal caliber and increased esophageal mural stiffness. The therapeutic benefits of topical corticosteroids and elimination diet therapy in resolving mucosal eosinophilic inflammation of the esophagus are evident. Available therapies, however, have demonstrated variable ability to reverse existing remodeling changes of the esophagus. Systemic therapies that include novel, targeted biologic agents have the potential of addressing subepithelial remodeling. Esophageal dilation remains a useful, adjunctive therapeutic maneuver in symptomatic adults with esophageal stricture. As novel treatments emerge, it is essential that therapeutic endpoints account for the fundamental contributions of esophageal remodeling to overall disease activity.

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Section: Effectiveness Of Available Therapies For Remodeling In Eoementioning

confidence: 99%

Clinical Implications and Pathogenesis of Esophageal Remodeling in Eosinophilic Esophagitis

Hirano

Aceves

2014

Gastroenterology Clinics of North America

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115

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“…29 For eosinophilic esophagitis (EoE), mainstays of treatment include food elimination diets, swallowed topical steroids and mechanical dilation for severe strictures. 41 …”

Section: Approved Therapies That Also Target Eosinophils or Eosinophimentioning

confidence: 99%

Novel Therapies for Eosinophilic Disorders

Bochner¹

2015

Immunology and Allergy Clinics of North America

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Synopsis Current therapies for eosinophilic disorders are limited. Most treatment approaches remain empirical, are not supported by data from controlled clinical trials, involve the off-label use of agents developed for treatment of other diseases, and tend to rely heavily on the use of glucocorticoids and other agents with significant toxicity. Also lacking are validated outcome metrics and clinically relevant biomarkers to help guide treatment choices, efficacy and assessment of disease activity. Over the last decade, great progress has been made in the discovery, preclinical development and clinical testing of a variety of biologics and small molecules that have the potential to directly or indirectly influence eosinophils, eosinophilic inflammation and the consequences of eosinophil activation. Particularly advanced are studies with biologics that target eosinophil-selective cytokines and their receptors. In addition, other therapies that have received FDA approval in recent years for non-eosinophil-related indications can be considered for testing in eosinophilic disorders. Overall, the landscape of therapeutic options for those suffering from eosinophilic disorders has never been brighter, with many new choices on the horizon.

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“…(7, 34–38) These genes have deep and diverse implications, as CLC is a marker that is now being used in a new minimally invasive test, the EoE string test,(39) CPA3 is a specific marker of mast cells,(9, 40, 41) IL4 and IL5 are targets of relevant therapeutic humanized antibody therapies being developed (e.g. anti–IL-5/anti–IL-5 receptor, anti–IL-4 receptor),(42–44) HPGDS can be blocked by a variety of drugs (e.g. cyclooxygenase inhibitors)(42) and VEGFR highlights consideration of anti- VEGF and related angiogenesis-based therapeutics, particularly for treatment of the cardinal EoE symptom dysphagia.…”

Section: Discussionmentioning

confidence: 99%

“…anti–IL-5/anti–IL-5 receptor, anti–IL-4 receptor),(42–44) HPGDS can be blocked by a variety of drugs (e.g. cyclooxygenase inhibitors)(42) and VEGFR highlights consideration of anti- VEGF and related angiogenesis-based therapeutics, particularly for treatment of the cardinal EoE symptom dysphagia. Furthermore, one gene ( CPA3 ) has been previously associated with chronic pelvic pain,(45) thereby supporting a role in patient symptomology.…”

Section: Discussionmentioning

confidence: 99%

Pediatric Eosinophilic Esophagitis Symptom Scores (PEESS v2.0) identify histologic and molecular correlates of the key clinical features of disease

Martin

Franciosi

Collins

et al. 2015

Journal of Allergy and Clinical Immunology

128

111

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Background The Pediatric Eosinophilic Esophagitis Symptom Score (PEESS® v2.0) measures patient-relevant outcomes. However, whether patient-identified domains (dysphagia, gastrointestinal reflux disease (GERD), nausea/vomiting, and pain) align with clinical symptomology and histopathologic and molecular features of eosinophilic esophagitis (EoE) is unclear. Objective The purpose of this study was to determine if clinical features of EoE, measured through the PEESS® v2.0, associate with histopathologic and molecular features of EoE. This represents a novel approach for analysis of allergic diseases, given the availability of allergic tissue biopsy specimens. Methods We systematically recruited treated and untreated, pediatric patients with EoE (aged 2–18 years) and examined parent proxy–reported symptoms using the PEESS® v2.0. Clinical symptomology was collected by questionnaire. Esophageal biopsy samples were quantified for levels of eosinophils, eosinophil peroxidase (EPX) immunohistochemical staining, and mast cells. Molecular features were assessed by the EoE Diagnostic Panel (94 EoE-related gene transcripts). Associations between domain scores and clinical symptoms and biologic features were analyzed using Wilcoxon Rank Sum and Spearman correlation. Results The PEESS® v2.0 domains correlated to specific parent-reported symptoms: dysphagia (p = 0.0012), GERD (p = 0.0001), and nausea/vomiting (p < 0.0001). Pain correlated with multiple symptoms (p < 0.0005). Dysphagia correlated most strongly with overall histopathology, particularly in the proximal esophagus (p ≤ 0.0049). Markers of esophageal activity (EPX) were significantly associated with dysphagia (strongest r = .37; p = 0.02). Eosinophil levels were more associated with pain (r = 0.27; p=0.06) than for dysphagia (r = 0.24; p = 0.13). The dysphagia domain correlated the most with esophageal gene transcript levels, predominantly with mast cell–specific genes. Conclusion We have 1) established a validated, parent proxy–report measure for pediatric EoE — the PEESS® v2.0; 2) verified that parent-proxy effectively captures symptoms; 3) determined that the dysphagia domain most closely aligns with symptoms and tissue-based molecular biomarkers; 4) established that symptoms correlate EPX staining; and 5) observed association between mast cells and dysphagia.

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Emerging drugs for eosinophilic esophagitis

Cited by 9 publications

References 64 publications

Clinical Implications and Pathogenesis of Esophageal Remodeling in Eosinophilic Esophagitis

Clinical Implications and Pathogenesis of Esophageal Remodeling in Eosinophilic Esophagitis

Novel Therapies for Eosinophilic Disorders

Pediatric Eosinophilic Esophagitis Symptom Scores (PEESS v2.0) identify histologic and molecular correlates of the key clinical features of disease

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