PURPOSE OF THE STUDY.
To evaluate the real-world efficacy of leukotriene-receptor antagonists (LTRAs) for the treatment of asthma by comparing LTRAs with both inhaled glucocorticoids for first-line therapy and long-acting β2 agonists (LABAs) for add-on therapy.
Patients aged 12 to 80 years were considered eligible if they had a Mini Asthma Quality of Life Questionnaire (MiniAQLQ) score of ≤6 or an Asthma Control Questionnaire (ACQ) score of ≥1. Trials were conducted at 53 primary care sites in the United Kingdom.
Patients were randomly assigned to an LTRA (n = 148) or inhaled glucocorticoid (n = 158) in the first-line therapy trial and an LTRA (n = 170) or an LABA (n = 182) in the step-up therapy trial. Patients were managed by their primary care provider during the 2-year trial period, and treatments were given in an open-label fashion. After the initial visit, patients were followed either by telephone or in the clinic at months 2, 6, 12, 18, and 24. Patients' MiniAQLQ score was the primary outcome measure. Secondary outcome measures included the ACQ score, the Royal College of Physicians 3-item asthma questionnaire score, the Mini Rhinoconjunctivitis Quality of Life Questionnaire score, and the frequency of asthma exacerbations that required oral glucocorticoids or hospitalization.
Over the 2-year treatment period, the mean MiniAQLQ score increased by 0.8 to 1.0 in both trials. Assessment of data at 2 months revealed noninferiority between LTRAs and inhaled glucocorticoids for first-line therapy on the basis of the primary outcome of MiniAQLQ score. At 2 years, results approached equivalence between the treatment groups in both trials; however, the data could not prove noninferiority. There were no significant differences between treatment groups regarding all other secondary outcome measures at both 2 months and 2 years. There was no significant difference in adherence rates in either trial.
Results at 2 months suggest comparable efficacy between LTRAs and inhaled glucocorticoids as first-line controller therapy and equivalence to LABAs as add-on therapy. Equivalence at 2 years was not proved for either trial.
Although LTRAs are a comparable option for both first-line and step-up therapy in asthma, true long-term equivalence has not been demonstrated. Results of previous randomized trials that examined LTRA use tend to support inhaled glucocorticoids as the preferred choice for first-line therapy and LABAs as the preferred choice for step-up therapy. The authors of a Cochrane review of 27 randomized controlled trials, mainly in adults with mild-to-moderate asthma, concluded that inhaled corticosteroid was more effective than LTRAs. A meta-analysis of 18 randomized controlled trials in children younger than 18 years with similar asthma found that inhaled corticosteroid was more effective than montelukast for preventing severe asthma exacerbations. The absence of a placebo group makes it difficult to judge whether the changes observed in MiniAQLQ score in either group from baseline are truly clinically meaningful. However, this study does provide a better, although not perfect, real-world perspective, with data approaching equivalence for LTRA use as both first-line and step-up therapy for asthma. Results from previous randomized controlled trials combined with data from this pragmatic study might not change how we currently practice but can guide us in our decision-making process more effectively in the real-world clinic setting.
- Copyright © 2011 by the American Academy of Pediatrics