title: Changing Paradigms in the Treatment of Severe Asthma: The Role of Biologic Therapies.
abstract: Cytokine antagonists are monoclonal antibodies that offer new treatment options for refractory asthma but will also increase complexity because they are effective only for patients with certain asthma subtypes that remain to be more clearly defined. The clinical and inflammatory heterogeneity within refractory asthma makes it difficult to manage the disease and to determine which, if any, biologic therapy is suitable for a specific patient. The purpose of this article is to provide a data-driven discussion to clarify the use of biologic therapies in patients with refractory asthma. We first discuss the epidemiology and pathophysiology of refractory asthma. We then interpret current evidence for biomarkers of eosinophilic or type 2-high asthma so that clinicians can determine potential treatments for patients based on knowledge of their effectiveness in specific asthma phenotypes. We then assess clinical data on the efficacy, safety, and mechanisms of action of approved and pipeline biologic therapies. We conclude by discussing the potential of phenotyping or endotyping refractory asthma and how biologic therapies can play a role in treating patients with refractory asthma.
authors.affiliation: Department of Medicine, Division of Allergy and Clinical Immunology, National Jewish Health, Denver, Colo. Electronic address: KatialR@njhealth.org.
authors.forename: Rohit K
authors.initials: RK
authors.lastname: Katial
authors.affiliation: Allergy, Immunology and Asthma Medical Group, Stockton, Calif.
authors.forename: Greg W
authors.initials: GW
authors.lastname: Bensch
authors.affiliation: Department of Medicine, Division of Allergy, Pulmonary and Critical Care, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
authors.forename: William W
authors.initials: WW
authors.lastname: Busse
authors.affiliation: Capital Allergy and Respiratory Disease Center, Sacramento, Calif.
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Chipps
authors.affiliation: Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, Colo; Division of Pulmonary Sciences and Critical Care Medicine, School of Medicine, University of Colorado at Denver, Anschutz Medical Campus, Aurora, Colo.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Denson
authors.affiliation: Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, Colo; Department of Biomedical Research, National Jewish Health, Denver, Colo.
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Gerber
authors.affiliation: Allergy and Asthma Clinical Research, Inc., Walnut Creek, Calif.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Jacobs
authors.affiliation: Department of Medicine, Asthma and Airway Disease Research Center, University of Arizona Health Sciences, Tucson, Ariz.
authors.forename: Monica
authors.initials: M
authors.lastname: Kraft
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colo.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Nair
authors.affiliation: Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, Colo.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Wechsler
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001249:Asthma / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy*; D001691:Biological Therapy; D015415:Biomarkers / Q000378:metabolism; D002170:Canada / Q000453:epidemiology; D003937:Diagnosis, Differential; D004804:Eosinophils / Q000276:immunology; D019317:Evidence-Based Medicine; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D010641:Phenotype; D012008:Recurrence; D014481:United States / Q000453:epidemiology
chemical_list: D018927:Anti-Asthmatic Agents; D000911:Antibodies, Monoclonal; D015415:Biomarkers
keywords: Biologic therapy; Eosinophil; FeNO; Monoclonal antibody; Periostin; Refractory asthma; Severe asthma