Leukotriene antagonists as first-line or add-on asthma-controller therapy

N Engl J Med. 2011 May 5;364(18):1695-707. doi: 10.1056/NEJMoa1010846.

Abstract

Background: Most randomized trials of treatment for asthma study highly selected patients under idealized conditions.

Methods: We conducted two parallel, multicenter, pragmatic trials to evaluate the real-world effectiveness of a leukotriene-receptor antagonist (LTRA) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta(2)-agonist (LABA) as add-on therapy in patients already receiving inhaled glucocorticoid therapy. Eligible primary care patients 12 to 80 years of age had impaired asthma-related quality of life (Mini Asthma Quality of Life Questionnaire [MiniAQLQ] score ≤6) or inadequate asthma control (Asthma Control Questionnaire [ACQ] score ≥1). We randomly assigned patients to 2 years of open-label therapy, under the care of their usual physician, with LTRA (148 patients) or an inhaled glucocorticoid (158 patients) in the first-line controller therapy trial and LTRA (170 patients) or LABA (182 patients) added to an inhaled glucocorticoid in the add-on therapy trial.

Results: Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials. At 2 months, differences in the MiniAQLQ scores between the two treatment groups met our definition of equivalence (95% confidence interval [CI] for an adjusted mean difference, -0.3 to 0.3). At 2 years, mean MiniAQLQ scores approached equivalence, with an adjusted mean difference between treatment groups of -0.11 (95% CI, -0.35 to 0.13) in the first-line controller therapy trial and of -0.11 (95% CI, -0.32 to 0.11) in the add-on therapy trial. Exacerbation rates and ACQ scores did not differ significantly between the two groups.

Conclusions: Study results at 2 months suggest that LTRA was equivalent to an inhaled glucocorticoid as first-line controller therapy and to LABA as add-on therapy for diverse primary care patients. Equivalence was not proved at 2 years. The interpretation of results of pragmatic research may be limited by the crossover between treatment groups and lack of a placebo group. (Funded by the National Coordinating Centre for Health Technology Assessment U.K. and others; Controlled Clinical Trials number, ISRCTN99132811.).

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Administration, Oral
  • Adolescent
  • Adrenergic beta-Agonists / therapeutic use*
  • Adult
  • Aged
  • Anti-Asthmatic Agents / therapeutic use*
  • Asthma / drug therapy*
  • Bronchodilator Agents / therapeutic use
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids / therapeutic use*
  • Humans
  • Leukotriene Antagonists / therapeutic use*
  • Male
  • Middle Aged
  • Quality of Life
  • Surveys and Questionnaires
  • Therapeutic Equivalency
  • Young Adult

Substances

  • Adrenergic beta-Agonists
  • Anti-Asthmatic Agents
  • Bronchodilator Agents
  • Glucocorticoids
  • Leukotriene Antagonists

Associated data

  • ISRCTN/ISRCTN99132811