New Targeted Therapies for Uncontrolled Asthma

J Allergy Clin Immunol Pract. 2019 May-Jun;7(5):1394-1403. doi: 10.1016/j.jaip.2019.03.022.

Abstract

Mechanistic studies have improved our understanding of molecular and cellular components involved in asthma and our ability to treat severe patients. An mAb directed against IgE (omalizumab) has become an established add-on therapy for patients with uncontrolled allergic asthma and mAbs specific for IL-5 (reslizumab, mepolizumab), IL-5R (benralizumab), and IL-4R (dupilumab) have been approved as add-on treatments for uncontrolled eosinophilic (type 2) asthma. While these medications have proven highly effective, some patients with severe allergic and/or eosinophilic asthma, as well as most patients with severe non-type-2 disease, have poorly controlled disease. Agents that have recently been evaluated in clinical trials include an antibody directed against thymic stromal lymphopoietin, small molecule antagonists to the chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) and the receptor for stem cell factor on mast cells (KIT), and a DNA enzyme directed at GATA3. Antibodies to IL-33 and its receptor, ST2, are being evaluated in ongoing clinical studies. In addition, a number of antagonists directed against other potential targets are under consideration for future trials, including IL-25, IL-6, TNF-like ligand 1A, CD6, and activated cell adhesion molecule (ALCAM). Clinical data from ongoing and future trials will be important in determining whether these new medications will offer benefits in place of or in addition to existing therapies for asthma.

Keywords: Asthma; Cytokine; Eosinophil; IL-33; Prostaglandin D2; TSLP.

Publication types

  • Review

MeSH terms

  • Activated-Leukocyte Cell Adhesion Molecule / immunology
  • Anti-Asthmatic Agents / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antigens, CD / immunology
  • Antigens, Differentiation, T-Lymphocyte / immunology
  • Asthma / drug therapy*
  • Asthma / immunology
  • Asthma / physiopathology
  • Cytokines / antagonists & inhibitors
  • Cytokines / immunology
  • DNA, Catalytic / therapeutic use
  • Eosinophils / immunology
  • GATA3 Transcription Factor
  • Humans
  • Imatinib Mesylate / therapeutic use
  • Indoleacetic Acids / therapeutic use
  • Interleukin-17 / antagonists & inhibitors
  • Interleukin-17 / immunology
  • Interleukin-6 / immunology
  • Lymphocytes / immunology
  • Mast Cells / immunology
  • Molecular Targeted Therapy
  • Omalizumab / therapeutic use
  • Proto-Oncogene Proteins c-kit / antagonists & inhibitors
  • Proto-Oncogene Proteins c-kit / immunology
  • Pyridines / therapeutic use
  • Receptors, Immunologic / antagonists & inhibitors
  • Receptors, Immunologic / immunology
  • Receptors, Interleukin-17 / antagonists & inhibitors
  • Receptors, Interleukin-17 / immunology
  • Receptors, Prostaglandin / antagonists & inhibitors
  • Receptors, Prostaglandin / immunology
  • Ribonucleases / therapeutic use
  • Th2 Cells / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 15 / antagonists & inhibitors
  • Tumor Necrosis Factor Ligand Superfamily Member 15 / immunology

Substances

  • Activated-Leukocyte Cell Adhesion Molecule
  • Anti-Asthmatic Agents
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD6 antigen
  • Cytokines
  • DNA, Catalytic
  • GATA3 Transcription Factor
  • IL17RA protein, human
  • Indoleacetic Acids
  • Interleukin-17
  • Interleukin-6
  • Pyridines
  • Receptors, Immunologic
  • Receptors, Interleukin-17
  • Receptors, Prostaglandin
  • TSLP protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 15
  • Omalizumab
  • fevipiprant
  • reslizumab
  • dupilumab
  • brodalumab
  • benralizumab
  • Imatinib Mesylate
  • mepolizumab
  • Proto-Oncogene Proteins c-kit
  • Ribonucleases
  • SB010 DNAzyme
  • tezepelumab
  • itolizumab
  • prostaglandin D2 receptor