Effectiveness of voriconazole in the treatment of Aspergillus fumigatus-associated asthma (EVITA3 study)

J Allergy Clin Immunol. 2014 Jul;134(1):33-9. doi: 10.1016/j.jaci.2013.09.050. Epub 2013 Nov 28.

Abstract

Background: IgE sensitization to Aspergillus fumigatus and a positive sputum fungal culture result are common in patients with refractory asthma. It is not clear whether these patients would benefit from antifungal treatment.

Objectives: We sought to determine whether a 3-month course of voriconazole improved asthma-related outcomes in patients with asthma who are IgE sensitized to A fumigatus.

Methods: Asthmatic patients who were IgE sensitized to A fumigatus with a history of at least 2 severe exacerbations in the previous 12 months were treated for 3 months with 200 mg of voriconazole twice daily, followed by observation for 9 months, in a double-blind, placebo-controlled, randomized design. Primary outcomes were improvement in quality of life at the end of the treatment period and a reduction in the number of severe exacerbations over the 12 months of the study.

Results: Sixty-five patients were randomized. Fifty-nine patients started treatment (32 receiving voriconazole and 27 receiving placebo) and were included in an intention-to-treat analysis. Fifty-six patients took the full 3 months of medication. Between the voriconazole and placebo groups, there were no significant differences in the number of severe exacerbations (1.16 vs 1.41 per patient per year, respectively; mean difference, 0.25; 95% CI, 0.19-0.31), quality of life (change in Asthma Quality of Life Questionnaire score, 0.68 vs 0.88; mean difference between groups, 0.2; 95% CI, -0.05 to -0.11), or any of our secondary outcome measures.

Conclusion: We were unable to show a beneficial effect of 3 months of treatment with voriconazole in patients with moderate-to-severe asthma who were IgE sensitized to A fumigatus on either the rate of severe exacerbations, quality of life, or other markers of asthma control.

Keywords: Aspergillus fumigatus; Refractory; allergic bronchopulmonary aspergillosis; asthma; eosinophils; exacerbations; mold; quality of life; severe asthma with fungal sensitization; voriconazole.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antifungal Agents / therapeutic use*
  • Aspergillosis / complications
  • Aspergillosis / drug therapy*
  • Aspergillosis / microbiology
  • Aspergillosis / pathology
  • Aspergillus fumigatus / drug effects
  • Aspergillus fumigatus / physiology
  • Asthma / complications
  • Asthma / drug therapy*
  • Asthma / microbiology
  • Asthma / pathology
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Immunoglobulin E / blood*
  • Intention to Treat Analysis
  • Male
  • Middle Aged
  • Quality of Life
  • Severity of Illness Index
  • Surveys and Questionnaires
  • Treatment Outcome
  • Voriconazole / therapeutic use*

Substances

  • Antifungal Agents
  • Immunoglobulin E
  • Voriconazole