Asthma phenotypes and the use of biologic medications in asthma and allergic disease: the next steps toward personalized care

J Allergy Clin Immunol. 2015 Feb;135(2):299-310; quiz 311. doi: 10.1016/j.jaci.2014.12.1871.

Abstract

Traditionally, asthma and allergic diseases have been defined by broad definitions and treated with nonspecific medications, including corticosteroids and bronchodilators. There is an increasing appreciation of heterogeneity within asthma and allergic diseases based primarily on recent cluster analyses, molecular phenotyping, biomarkers, and differential responses to targeted and nontargeted therapies. These pioneering studies have led to successful therapeutic trials of molecularly targeted therapies in defined phenotypes. This review analyzed randomized double-blind, placebo-controlled trials of molecularly targeted therapies in defined allergic disease and asthma phenotypes. IgE was the first successful biological target used in patients with allergic disease and asthma. This review shows that therapies targeting the canonical type 2 cytokines IL-4, IL-5, and IL-13 have shown consistent efficacy, especially in asthmatic patients with evidence of TH2/type 2 inflammation ("type 2 high"). As of yet, there are no successful trials of targeted therapies in asthmatic patients without evidence for type 2 inflammation. We conclude that further refinement of type 2 therapies to specific type 2 phenotypes and novel approaches for patients without type 2 inflammation are needed for asthma and allergic disease treatment.

Keywords: Asthma phenotypes; IL-13; IL-4; IL-5; IgE; T(H)2/type 2 inflammation; biologic therapies; eosinophils.

Publication types

  • Review

MeSH terms

  • Anti-Asthmatic Agents / pharmacology
  • Anti-Asthmatic Agents / therapeutic use*
  • Asthma / diagnosis*
  • Asthma / drug therapy*
  • Asthma / genetics
  • Asthma / immunology
  • Asthma / metabolism
  • Biological Factors / pharmacology
  • Biological Factors / therapeutic use*
  • Biomarkers / metabolism
  • Cytokines / antagonists & inhibitors
  • Cytokines / genetics
  • Cytokines / metabolism
  • Eosinophils / drug effects
  • Eosinophils / immunology
  • Eosinophils / metabolism
  • Humans
  • Hypersensitivity / diagnosis*
  • Hypersensitivity / drug therapy*
  • Hypersensitivity / genetics
  • Hypersensitivity / immunology
  • Hypersensitivity / metabolism
  • Immunoglobulin E / immunology
  • Neutrophils / drug effects
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Pharmacogenetics
  • Phenotype*
  • Precision Medicine
  • Signal Transduction / drug effects
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Th2 Cells / metabolism

Substances

  • Anti-Asthmatic Agents
  • Biological Factors
  • Biomarkers
  • Cytokines
  • Immunoglobulin E