Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2016
Characterization of asthma endotypes: implications for therapy.
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Stokes Jeffrey R, Casale Thomas B
Аннотация
OBJECTIVE: To describe the concept of precision medicine in treating severe asthma and the utility of relevant biomarkers.
DATA SOURCES: PubMed was searched for published articles on human clinical trials using biologics for T-helper type 2 cell (TH2)-low and TH2-high asthma.
STUDY SELECTIONS: Studies were selected if they were double-masked, randomized, placebo-controlled trials published in peer-reviewed journals and relevant to the topic.
RESULTS: Multiple immune response modifiers have been evaluated in TH2-high asthma geared at blocking interleukin (IL)-5, IL-13, immunoglobulin E, prostaglandin D2, and other pathways. Currently, 3 immune response modifiers approved by the Food and Drug Administration are available for treating severe TH2-high asthma (1 anti-immunoglobulin E and 2 anti-IL-5 monoclonal antibodies) and other TH2-high therapies are in various stages of clinical development. Thus far, many of the TH2-high therapies have shown better efficacy when certain biomarkers are elevated, especially blood eosinophils. The TH2-low endotype does not have any readily available point-of-care biomarkers, so TH2-low asthma is often diagnosed based on a lack of TH2-high biomarkers. These patients tend to have greater resistance to steroids and the development of therapies has lagged behind that for TH2-high asthma.
CONCLUSION: Two major endotypes for asthma have been described, TH2-high, manifested by increased eosinophils in the sputum and airways of patients, and TH2-low, with increased neutrophils or a pauci-granulocytic profile. Using these classifications and specific biomarkers has led to promising new therapeutics, especially for TH2-high asthma.
DATA SOURCES: PubMed was searched for published articles on human clinical trials using biologics for T-helper type 2 cell (TH2)-low and TH2-high asthma.
STUDY SELECTIONS: Studies were selected if they were double-masked, randomized, placebo-controlled trials published in peer-reviewed journals and relevant to the topic.
RESULTS: Multiple immune response modifiers have been evaluated in TH2-high asthma geared at blocking interleukin (IL)-5, IL-13, immunoglobulin E, prostaglandin D2, and other pathways. Currently, 3 immune response modifiers approved by the Food and Drug Administration are available for treating severe TH2-high asthma (1 anti-immunoglobulin E and 2 anti-IL-5 monoclonal antibodies) and other TH2-high therapies are in various stages of clinical development. Thus far, many of the TH2-high therapies have shown better efficacy when certain biomarkers are elevated, especially blood eosinophils. The TH2-low endotype does not have any readily available point-of-care biomarkers, so TH2-low asthma is often diagnosed based on a lack of TH2-high biomarkers. These patients tend to have greater resistance to steroids and the development of therapies has lagged behind that for TH2-high asthma.
CONCLUSION: Two major endotypes for asthma have been described, TH2-high, manifested by increased eosinophils in the sputum and airways of patients, and TH2-low, with increased neutrophils or a pauci-granulocytic profile. Using these classifications and specific biomarkers has led to promising new therapeutics, especially for TH2-high asthma.