Inhaled corticosteroids are first-line medications for daily control of persistent asthma. Leukotriene receptor antagonists have shown a comparable effectiveness in controlling adult asthma relating to a variety of endpoints. Garcia and colleagues compared the effectiveness of a leukotriene inhibitor with an inhaled corticosteroid in a group of patients six to 14 years of age with mild persistent asthma.
In this year-long trial, montelukast (Singulair) administered orally once daily was compared with twice-daily administration of inhaled fluticasone (Flovent), starting with a four-week, single-blind placebo run-in period. It was a double-blind study, and dummy placebos were used. Forced expiratory volume in one second (FEV1) was measured at month intervals at office visits. Patients also recorded beta agonist use, additional asthma medication use, and unscheduled physician or emergency department visits.
Outcome measures included the number of rescue-free days. Rescue-free days are defined as days with no use of any asthma rescue medications or unscheduled asthma-related health care visits. Other endpoints included change in predicted FEV1 values, of patients requiring asthma medications or having an asthma attack, average number of days a beta agonist was used, and change in eosinophil counts. Statistical evaluation determined whether montelukast was not inferior to fluticasone based on a lower limit of a confidence interval higher than –7 percent, or two days a month.
Of the 994 participants, 495 were randomized to montelukast and 499 to fluticasone. The difference of –2.8 percent, or less than one day per month, was above the noninferiority limit when using percentage of rescue-free days to determine whether montelukast was not inferior to fluticasone. Average percentage of FEV1 increased from a baseline of 88.1 to 89.0 percent in the montelukast group and from 88.9 to 91.7 percent in the fluticasone group. Although these findings showed montelukast’s noninferiority to fluticasone, they did favor fluticasone. Beta agonist use decreased by 22.7 percent in the montelukast group compared with 25.4 percent in the fluticasone group. In the montelukast group, the proportion of patients requiring additional rescue medication was 20.7 percent compared with 13.5 percent in the fluticasone group. However, this difference was noted only when use was less than one day per month. Patients were more likely to have an asthma attack with montelukast than with fluticasone (32.2 versus 25.6 percent, respectively). Quality of life improved in both groups, and eosinophilia declined. Compliance rates were similar in both groups.
The authors conclude that montelukast was not inferior to fluticasone in controlling asthma based on rescue-free days, changes in FEV1, and days with beta agonist use. Fluticasone performed better by some measures. Some studies, including this one, show lower growth with systemic steroids, strengthening the case for montelukast as an alternative for mild persistent asthma.
In an accompanying editorial, Goodman reminds the reader that noninferiority trials are used in postmarketing studies to establish the equivalence of one medication to another. Because these trials often are funded by pharmaceutical companies, the results must be interpreted in the light of the sponsor’s desired outcome. Goodman states that this trial is unlikely to change practice because the benefit of inhaled corticosteroids for adults is solidly established and the extrapolation to children has become standard.