A proof-of-concept, randomized, controlled trial of omalizumab in patients with severe, difficult-to-control, nonatopic asthma

Chest. 2013 Aug;144(2):411-419. doi: 10.1378/chest.12-1961.

Abstract

Background: While up to 50% of patients with severe asthma have no evidence of allergy, IgE has been linked to asthma, irrespective of atopic status. Omalizumab, an anti-IgE monoclonal antibody, is reported to significantly benefit a subset of patients with severe, persistent, allergic asthma. Therefore, we investigated whether omalizumab has biologic and clinical effects in patients with refractory nonatopic asthma.

Methods: Forty-one adult patients who, despite daily treatment with or without maintenance oral corticosteroids, had severe, nonatopic, refractory asthma according to GINA (Global Initiative for Asthma) step 4, were randomized to receive omalizumab or placebo in a 1:1 ratio. The primary end point was the change in expression of high-affinity IgE receptor (FcεRI) on blood basophils and plasmacytoid dendritic cells (pDC2) after 16 weeks. The impact of omalizumab on lung function and clinical variables was also examined.

Results: Compared with placebo, omalizumab resulted in a statistically significant reduction in FcεRI expression on basophils and pDC2 (P < .001). The omalizumab group also showed an overall increase in FEV1 compared with baseline (+250 mL, P = .032; +9.9%, P = .029). A trend toward improvement in global evaluation of treatment effectiveness and asthma exacerbation rate was also observed.

Conclusions: Omalizumab negatively regulates FcεRI expression in patients with severe nonatopic asthma, as it does in severe atopic asthma. Omalizumab may have a therapeutic role in severe nonatopic asthma. Nonetheless, our preliminary findings support further investigation to better assess the clinical efficacy of omalizumab.

Trial registry: ClinicalTrials.gov; No.: NCT01007149; URL: www.clinicaltrials.gov and European Clinical Trials Database, EudraCT; No.: 2009-010937-38; URL: https://www.clinicaltrialsregister.eu.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Aged
  • Anti-Asthmatic Agents / therapeutic use*
  • Antibodies, Anti-Idiotypic / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Asthma / drug therapy*
  • Asthma / immunology
  • Asthma / physiopathology
  • Double-Blind Method
  • Female
  • Humans
  • Immunoglobulin E / immunology
  • Male
  • Middle Aged
  • Omalizumab
  • Placebos
  • Respiratory Function Tests
  • Treatment Outcome

Substances

  • Adrenal Cortex Hormones
  • Anti-Asthmatic Agents
  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal, Humanized
  • Placebos
  • Omalizumab
  • Immunoglobulin E

Associated data

  • ClinicalTrials.gov/NCT01007149