Inhaled glucocorticoids are now the cornerstone of asthma therapy. When initial therapy is insufficient, treatment strategies include adding long-acting beta2 agonists or anti-leukotrienes. Although anti-leukotrienes are increasingly prescribed as add-on therapy, their efficacy when used alone is unclear. Ducharme conducted a meta-analysis to assess the safety and efficacy of oral anti-leukotrienes as add-on therapy in asthma and the glucocorticoid-sparing effect these drugs have during tapering of inhaled steroids.
Relevant clinical trials and review articles were identified by a search of electronic databases, references of articles, and abstracts of specialty conferences. Pharmaceutical companies were contacted for data from unpublished trials. Eligible trials concerned the use of add-on anti-leukotrienes for at least 28 days in patients who used inhaled glucocorticoids for asthma. The primary outcome was the number of asthma exacerbations that required rescue treatment with systemic glucocorticoids. Secondary outcomes included change in pulmonary-function test results, symptoms of asthma, quality-of-life measures, use of rescue beta2 agonists, hospital admission for treatment of asthma, and adverse effects of the medication.
More than 370 citations were reviewed, but only 13 trials met the criteria for inclusion. Ten of these trials were rated high-quality (using Jadad's instrument), and in three trials, treatment allocation was not concealed. Only two trials directly assessed add-on therapy of anti-leukotrienes in licensed dosages. At these dosages, a non-statistically significant reduction in risk of exacerbations was reported in adults, and no reduction was reported in children. Pooling the results of these two studies showed modest but significant benefit in terms of morning peak expiratory flow rate, use of beta2 agonists, and eosinophil counts. No changes were noted in other variables. Two trials that used higher dosages of anti-leukotrienes showed significant benefit in forced expiratory volume in one second, peak expiratory flow, use of rescue beta2 agonists, and asthma symptoms.
Data were limited on the comparison between adding anti-leukotriene therapy to inhaled glucocorticoids and escalating the dosage of steroids. The two available studies used higher-than-licensed dosages of anti-leukotrienes and showed no difference in the strategies. Similarly, few trials were found that used anti-leukotrienes during tapering of inhaled glucocorticoids, and they showed no difference in the lowest achieved dosage; however, when anti-leukotriene therapy was used, withdrawals because of poor asthma control were reduced.
The author concludes that the addition of licensed dosages of anti-leukotrienes to inhaled glucocorticoid therapy may modestly improve asthma control, but that this appears to be a less effective strategy than increasing the dosage of glucocorticoids. Anti-leukotrienes also show some positive effect during tapering of inhaled glucocorticoids, but more research on these drugs at licensed dosages is necessary before clinical guidance can be given.