Noninvasive biomarkers that predict treatment benefit from biologic therapies in asthma

Ann Am Thorac Soc. 2013 Dec;10 Suppl:S206-13. doi: 10.1513/AnnalsATS.201303-047AW.

Abstract

Although human asthma is commonly regarded as an allergic disorder characterized by type 2 cytokine expression and eosinophilic inflammation in the airways, it is clearly heterogeneous with respect to airway inflammation. Genomic approaches have identified heterogeneous gene expression patterns in asthmatic airways corresponding to the degree of type 2 cytokine expression and eosinophilic inflammation. These gene expression patterns have led to the identification of candidate biomarkers of eosinophilic airway inflammation that do not require bronchoscopy or sputum induction. Candidate biologic therapies targeting mediators of type 2 airway inflammation have progressed through clinical studies in patients with moderate-severe asthma in recent years. Serum periostin, fractional exhaled nitric oxide, and blood eosinophil counts have emerged as predictive and pharmacodynamic biomarkers that may enrich for clinical benefit in clinical studies of biologic therapies targeting interleukin-13, interleukin-5, and immunoglobulin E. Because airway inflammation and associated biomarkers are continuously distributed across the population of patients with asthma, future efforts should be directed at identifying clinically relevant biomarker cutoffs to target these and other novel therapeutics to the most appropriate patient populations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Asthmatic Agents / therapeutic use*
  • Antibodies, Anti-Idiotypic / therapeutic use
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Asthma / drug therapy*
  • Asthma / genetics
  • Asthma / metabolism
  • Biomarkers / metabolism
  • Breath Tests
  • Cell Adhesion Molecules / metabolism
  • Drug Discovery
  • Eosinophils
  • Humans
  • Immunologic Factors / therapeutic use*
  • Interleukin-4 / therapeutic use
  • Leukocyte Count
  • Nitric Oxide / metabolism
  • Omalizumab
  • Treatment Outcome

Substances

  • AMG 317
  • Anti-Asthmatic Agents
  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Cell Adhesion Molecules
  • Immunologic Factors
  • POSTN protein, human
  • pitrakinra
  • tralokinumab
  • Interleukin-4
  • Omalizumab
  • Nitric Oxide
  • reslizumab
  • benralizumab
  • mepolizumab
  • lebrikizumab