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Novel Therapies for Eosinophilic Disorders.

ABSTRACT: 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. 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.

SUBMITTER: Bochner BS

PROVIDER: S-EPMC4515571 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Novel Therapies for Eosinophilic Disorders.

Bochner Bruce S BS

Immunology and allergy clinics of North America 20150801 3

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. Great progress has been made in the discovery, preclinical development, and clinical testing of a variety of biologics and small molecules that have the potentia ...[more]

PMID: 26209901

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Project description:Asthma is characterized by episodic, reversible airflow obstruction associated with variable levels of inflammation. Over the past several decades, there has been an increasing appreciation that the clinical presentation of asthma comprises a diverse set of underlying pathologies. Rather than being viewed as a single disease entity, asthma is now thought of as a clinical syndrome with the involvement of multiple pathological mechanisms. While it is appreciated that eosinophilia is present in only a subset of patients, it remains a key feature of asthma and other eosinophilic disorders such as atopic dermatitis, eosinophilic esophagitis, and chronic rhinosinusitis with nasal polyps. Eosinophils are bone marrow-derived leukocytes present in low numbers in health; however, during disease the type 2 cytokines [interleukins (IL)-4, -5, and -13] can induce rapid eosinophilopoiesis, prolonged eosinophil survival, and trafficking to the site of injury. In diseases such as allergic asthma there is an aberrant inflammatory response leading to eosinophilia, tissue damage, and airway pathology. IL-13 is a pleiotropic type 2 cytokine that has been shown to be integral in the pathogenesis of asthma and other eosinophilic disorders. IL-13 levels are elevated in animal models of eosinophilic inflammation and in the blood and tissue of patients diagnosed with eosinophilic disorders. IL-13 signaling elicits many pathogenic mechanisms including the promotion of eosinophil survival, activation, and trafficking. Data from preclinical models and clinical trials of IL-13 inhibitors in patients have revealed mechanistic insights into the role of this cytokine in driving eosinophilia. Promising results from clinical trials further support a key mechanistic role of IL-13 in asthma and other eosinophilic disorders. Here, we provide a perspective on the role of IL-13 in asthma and other eosinophilic disorders and describe ongoing clinical trials targeting this pathway in patients with significant unmet medical needs.

Dataset Information

Novel Therapies for Eosinophilic Disorders.

Publications

Novel Therapies for Eosinophilic Disorders.

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