Leukotriene Receptor Antagonists and Asthma Treatment

According to researchers, although double-blind, randomized, controlled trials provide dependable evidence in establishing the efficacy of therapeutic interventions, such proof does not guarantee the effectiveness of a particular therapy in a diverse patient population in a clinical practice. In the case of asthma, the researchers noted, the majority of trials exclude approximately 95% of patients with a current diagnosis of asthma, including “smokers and those who have insufficient bronchodilator reversibility or impaired pulmonary functions.” Furthermore, trial design rarely accounts for the “long-term factors that clinicians must consider, such as adherence, inhaler technique, tolerability, and physician and patient preferences,” they added. Inhaled glucocorticoids are recommended as firstline treatment for asthma control in patients with mild persistent asthma; these agents have little effect on the formation or action of cysteinyl leukotrienes, inflammatory mediators in asthma. Trials have demonstrated the efficacy of leukotriene receptor antagonists (LTRAs), but results have been mixed. Some trials suggest that LTRAs are less efficacious than inhaled glucocorticoids for mild persistent asthma; others report similar overall asthma control and proportions of patients meeting asthma control criteria. The researchers recently conducted 2 parallel, multicenter, pragmatic trials to evaluate the real-world effectiveness of an LTRA compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta2-agonist (LABA) as add-on therapy in patients receiving inhaled glucocorticoid therapy. Results were reported in the New England Journal of Medicine [2011;364(18):1695-1707]. Inclusion criteria included age 12 to 80 years, diagnosis of asthma, impaired asthma-related quality of life (Mini Asthma Quality of Life Questionnaire [MiniAQLQ] score of ≤6) or inadequate asthma control (Asthma Control Questionnaire [ACQ] score ≤1). The patients were randomly assigned to 2 years of open-label therapy, under the care of their regular physician, with an LTRA (n=148) or an inhaled glucocorticoid (n=158) in the first-line controller therapy trial and an LTRA (n=170) or LABA (n=182) added to an inhaled glucocorticoid in the add-on therapy trial. The primary outcome measure was the MiniAQLQ score. Secondary outcome measures included the ACQ score, scores on other asthma-related scales, and the frequency of asthma exacerbations (the need for an oral course of glucocorticoids or hospitalization for asthma). Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials. At 2 months, the scores were equivalent in the 2 treatment groups; at 2 years, mean MiniAQLQ scores approached the researchers’ definition of equivalence, with an adjusted mean difference between treatment groups of –0.11 (95% confidence interval [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. There was no significant difference in exacerbation rates and ACQ scores between the 2 groups. The researchers cautioned that because there were very few study patients <25 years of age, the study results apply only to adults. They also said that in general, “caution should be applied in extrapolating results from randomized clinical trials to the broad population of patients with asthma who are treated in community settings."