Investigational agents for asthma
- Richard J Martin, MD
Richard J Martin, MD
- Professor of Medicine
- University of Colorado Denver, School of Medicine
- Section Editors
- Bruce S Bochner, MD
Bruce S Bochner, MD
- Editor-in-Chief — Allergy and Immunology
- Section Editor — Adult Allergy; Asthma
- Samuel M Feinberg Professor of Medicine
- Northwestern University Feinberg School of Medicine
- Robert A Wood, MD
Robert A Wood, MD
- Editor-in-Chief — Allergy and Immunology
- Section Editor — Pediatric Allergy
- Professor of Pediatrics
- Johns Hopkins University School of Medicine
The standard treatment of patients with asthma is based upon trigger avoidance, bronchodilation, and anti-inflammatory therapy. Beta agonists, inhaled and systemic glucocorticoids, leukotriene modifiers, omalizumab, and, to a lesser extent, methylxanthines and anticholinergics all have a role in the conventional treatment of asthma. However, some patients do not achieve adequate control of their asthma with conventional therapy or experience adverse effects with conventional agents. Ongoing research is attempting to identify more effective and less toxic agents to control asthma.
Investigational approaches to asthma management, both promising and unsuccessful, will be reviewed here. Standard treatment regimens for asthma and complementary, alternative, and integrative approaches are discussed separately. (See "An overview of asthma management" and "Complementary, alternative, and integrative therapies for asthma".)
PROSTAGLANDIN D2 RECEPTOR ANTAGONIST
Prostaglandins are one of the major groups of metabolites (along with thromboxanes and leukotrienes) derived from arachidonic acid (figure 1). Prostaglandin D2 (PGD2) is the predominant prostaglandin produced by mast cells and is also produced by Th2 lymphocytes and dendritic cells. It has bronchoconstrictive and chemokinetic effects that may contribute to asthma pathogenesis, such as being a potent eosinophil chemoattractant. PGD2 acts on the PGD2 receptor 2 (DP2 receptor) on mast cells, eosinophils, and basophils. The DP2 receptor mediates migration of Th2 lymphocytes, delays Th2 cell apoptosis and stimulation of Th2 cells to produce interleukin-4 (IL-4), IL-5, and IL-13 among other effects. (See "Pathogenesis of asthma", section on 'Early and late phase reactions'.)
Fevipiprant is an investigational DP2 receptor antagonist that was assessed in a clinical trial of 61 patients with moderate-to-severe persistent asthma and an elevated sputum eosinophil count (≥2 percent) . The participants were randomly assigned to fevipiprant 225 mg or placebo orally twice a day for 12 weeks. The sputum eosinophil percentage decreased significantly from an initial geometric mean of 5.4 (95% CI 3.1-9.6) to 1.1 (95% CI 0.7-1.9) in the fevipiprant group and from 4.6 (95% CI 2.5-8.7) to 3.9 (95% CI 2.3-6.7) in the placebo group. Symptoms were assessed using the ACQ-7 questionnaire and were not different between groups. The quality of life questionnaire AQLQ score showed improvement in the fevipiprant group. A borderline benefit was noted in postbronchodilator, but not prebronchodilator, spirometry. No deaths or serious adverse events were reported. Further study is needed to explore the effects of fevipiprant on lung function and asthma exacerbations.
Several biologic agents targeting steps in the cascade of cytokines implicated in asthma inflammation have been developed in hopes of ameliorating the inflammation that underlies chronic asthma. A novel glucocorticoid receptor agonist approaches immunomodulation in a different way, by activating the glucocorticoid receptor, but possibly without the usual adverse effects of traditional glucocorticoids. (See "Pathogenesis of asthma", section on 'Airway inflammation'.)
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- PROSTAGLANDIN D2 RECEPTOR ANTAGONIST
- BIOLOGIC AGENTS
- Anti-IgE agents
- Anti-IL-2R antibody
- Anti-IL-5 therapy
- Anti-IL-13 antibodies
- Anti-lL-4 receptor alpha subunit antibody
- Anti-thymic stromal lymphopoietin
- GATA3-specific DNAzyme
- Novel glucocorticoid receptor agonist
- IMMUNOMODULATORY AGENTS WITH SIGNIFICANT LIMITATIONS
- Macrolide antibiotics
- Anti-TNF-alpha agents
- NEBULIZED AGENTS
- Nebulized lidocaine
- Nebulized heparin
- ANTIFUNGAL AGENTS
- SUMMARY AND RECOMMENDATIONS