A proof of concept study to evaluate putative benefits of montelukast in moderate persistent asthmatics

Abstract

Aims: Whether chronic dosing with montelukast confers benefit in patients with moderate to severe asthma remains to be fully established. A proof of concept study was performed evaluating putative benefits with montelukast in moderate persistent asthmatics who were taken off inhaled corticosteroids (ICS) and switched to salmeterol. The latter was done to dissociate the effects of montelukast from ICS.

Methods: Twenty moderate to severe persistent asthmatics completed a randomized double-blind crossover study. Subjects received montelukast 10 mg daily or placebo for 2 weeks each. This was preceded by a 2-week run-in when ICS were discontinued and salmeterol started, and used on a regular basis throughout the study. Measurements were made after run-in and after both randomized treatments.

Results: There were no significant sequence effects for responses as to whether placebo or montelukast were given first or second. Methacholine PD20 values after run-in, first and second placebo were 63 micro g, 60 micro g and 64 micro g, respectively (corresponding to 2, 4 and 6 weeks of ICS washout, respectively). Lung function deteriorated pre vs post run-in, which was significant (P < 0.05) for FEF25-75 % predicted. Montelukast conferred significant (P < 0.05) improvements as change from post run-in compared with placebo in methacholine PD20, FEV1 % predicted, FEF25-75 % predicted, diurnal peak expiratory flow, symptoms and salbutamol use. For the primary outcome of methacholine PD20, this amounted to a 1.6-fold difference (95% CI 1.1, 2.5).

Conclusions: In moderate persistent asthmatics switched from taking ICS to salmeterol alone, adding montelukast conferred significant benefits on all parameters of asthma control. Further studies are indicated to evaluate whether montelukast exhibits additive effects to ICS/long-acting beta2-adrenoceptor agonist combination inhalers upon clinically important outcomes.

Figure 1

Study flow diagram.

Figure 2

Drop out flow diagram.

Figure 3

Values for (a) FEV₁ and (b) FEF_25-75 at pre run-in and following post run-in and randomized treatments. *Denotes significant (P < 0.05) difference from pre run-in; †denotes significant (P < 0.05) difference from placebo.

Figure 4

Individual data for PD₂₀ fold shift from post run-in for placebo and montelukast illustrated on a log₂ scale to depict doubling dose shifts. A fold shift < 1 denotes worsening and > 1 denotes improvement as compared with post run-in values. ○ and denote placebo and ▵ montelukast, respectively, with solid lines showing individual change for n = 16 patients who underwent challenges on both randomized treatments. Geometric mean fold shifts (geometric SE) are shown.