title: Monoclonal antibodies for the treatment of refractory asthma.
abstract: OBJECTIVE
  A small proportion of patients with asthma have severe disease characterized by persistent airflow obstruction, airway hyperresponsiveness and eosinophilic airway inflammation. This review focuses on the clinical efficacy of inhibiting T helper 2-cytokine-mediated inflammatory responses using monoclonal antibodies directed against immunoglobulin E (IgE), interleukin (IL)-5, and IL-4/IL-13 in patients with severe refractory asthma.
  
  
  RESULTS
  The heterogeneity of airway inflammation in severe asthma has led to the recognition of multiple pathophysiologically distinct severe asthma endotypes. Biomarkers are being developed and evaluated to identify these endotypes and to guide the use of specific biologics in the appropriate patients who remain uncontrolled on high doses of inhaled corticosteroids and long-acting bronchodilators or oral corticosteroids. Examples include the efficacy of omalizumab in patients with severe refractory atopic asthma characterized by raised serum total IgE, mepolizumab, reslizumab, and benralizumab in patients with recurrent eosinophilic exacerbations characterized by blood and sputum eosinophilia despite high doses of corticosteroids, and lebrikizumab, pitrakinra, dupilumab, and tralokinumab that target the IL-4/IL-13 signalling pathways in patients with eosinophilic asthma or raised serum periostin.
  
  
  CONCLUSIONS
  In severe refractory asthma, both an understanding of the underlying pathophysiologic mechanisms driving airway inflammation and the identification of appropriate biomarkers in individual patients are critical in guiding the use of biologics and monoclonal antibodies that target the specific pathological processes.
authors.affiliation: Division of Respirology, Department of Medicine, St Joseph's Healthcare and McMaster University, Hamilton, Ontario, Canada.
authors.forename: Nathan
authors.initials: N
authors.lastname: Hambly
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Nair
mesh_terms: D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D015848:Interleukin-5 / Q000276:immunology / Q000378:metabolism; D012720:Severity of Illness Index; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D018927:Anti-Asthmatic Agents; D000911:Antibodies, Monoclonal; D018793:Interleukin-13; D015848:Interleukin-5; D015847:Interleukin-4; D007073:Immunoglobulin E