Anti-leukotrienes as add-on therapy to inhaled glucocorticoids in patients with asthma: systematic review of current evidence

Abstract

Objectives: To examine the evidence for the efficacy and glucocorticoid sparing effect of oral anti-leukotrienes taken daily as add-on therapy to inhaled glucocorticoids in patients with asthma.

Design: Systematic review of randomised controlled trials of children and adults with asthma comparing the addition of anti-leukotrienes or placebo to inhaled glucocorticoids.

Main outcome measures: The rate of exacerbations of asthma requiring rescue systemic glucocorticoids when the intervention was compared to the same or double dose of inhaled glucocorticoids, and the glucocorticoid sparing effect when the intervention was aimed at tapering the glucocorticoid.

Results: Of 376 citations, 13 were included: 12 in adult patients and one in children. The addition of licensed doses of anti-leukotrienes to inhaled glucocorticoids resulted in a non-significant reduction in the risk of exacerbations requiring systemic steroids (two trials; relative risk 0.61, 95% confidence interval 0.36 to 1.05). No trials comparing the use of anti-leukotrienes with double the dose of inhaled glucocorticoids could be pooled. The use of anti-leukotrienes resulted in no overall group difference in the lowest achieved dose of inhaled glucocorticoids (three trials; weighted mean difference -44.43 microg/day, -147.87 to 59.02: random effect model) but was associated with a reduction in withdrawals owing to poor asthma control (four trials; relative risk 0.56, 0.35 to 0.89).

Conclusions: The addition of anti-leukotrienes to inhaled glucocorticoids may modestly improve asthma control compared with inhaled glucocorticoids alone but this strategy cannot be recommended as a substitute for increasing the dose of inhaled glucocorticoids. The addition of anti-leukotrienes is possibly associated with superior asthma control after tapering of glucocorticoids, but the glucocorticoids sparing effect cannot be quantified at present.

Figure 1

Flow diagram of trials selected for inclusion in review. Cochrane Library has list of excluded randomised controlled trials, with reason for ineligibility

Figure 2

Anti-leukotrienes versus placebo as add-on therapy to inhaled glucocorticoids

Figure 3

Anti-leukotrienes as add-on therapy to inhaled glucocorticoids versus double dose of inhaled glucocorticoids. There was no aggregation of data across different doses of zafirlukast

Figure 4

Anti-leukotrienes versus placebo with tapering doses of inhaled glucocorticoids