Leukotriene-receptor antagonists were just as effective as inhaled glucocorticoids as first-line controller and add-on asthma therapy in a diverse primary care patient population, results from two “real-life” trials indicate.
The two drugs were equivalent when administered as monotherapy to reduce asthma symptoms after two months, and approached equivalence at two years, David Price, MD, of the University of Aberdeen in Scotland, and colleagues wrote in the New England Journal of Medicine.
Although current asthma treatment guidelines recommend inhaled glucocorticoids as the gold standard controller medication for patients with mild persistent asthma, according to background information in the study, the medication has little effect on the formation or action of cysteinyl leukotrienes — a type of inflammatory mediator.
Results from previous randomized controlled clinical trials comparing LTRAs and inhaled glucocorticoids have been mixed. So Price and colleagues sought to evaluate the medications’ effect on asthma-related quality of life in “real-world conditions.”
The first trial evaluated the two medications as first line therapies, and the other trial analyzed outcomes in patients with poorly controlled asthma that were given either an LTRA or a long-acting beta2-agonist (LABA) in addition to glucocorticoids. All patients were treated by their usual primary care health providers.
For the first-line trial, 148 patients were assigned to an LTRA and 158 received a glucocorticoid. For the add-on trial, 170 were assigned to an LTRA and 182 were given a LABA.
After two months of therapy, quality of life scores among patients receiving LTRAs and glucocorticoids were equivalent, the researchers found. After two years the confidence intervals fell just short of the study limits established to define equivalence (-0.35 to 0.13 for first-line and -0.32 to 0.11 for add-on compared with -0.3 to 0.3 as the standard).
There were no significant differences between treatment groups on any of the secondary outcomes, which included asthma control and frequency of asthma exacerbations, or in rescue bronchodilator use.
However, medication adherence was significantly better among patients assigned to LTRAs — 65% versus 41% in the first-line study and 74% versus 46% in the add-on trial.
Despite improvements in adherence, the researchers warned that about a quarter of patients in the add-on group were switched to an LABA or were prescribed an add-on LABA. “The crossover between treatment groups was regrettable but unavoidable, since this was a pragmatic trial and we allowed usual practice to occur,” the researchers wrote.
Only patients aged 25 years and older were included in the study, thus limiting the results to adults.
In an accompanying editorial Sven-Erik Dahlén, MD, PhD, of the Karolinska Institute, and colleagues wrote that these trial results “send an important message” to clinicians, despite the limitations
“We treat patients to help them cope with their asthma today,” they wrote. “The two studies described by Price et al. show that oral leukotriene modifiers provide an alternative treatment that may help patients pursue their activities of daily life as effectively as inhaled glucocorticoids do.”
They noted that the once daily pill formulation of LTRAs may be easier for patients to take than using an inhaler, and added that there may be additional beneficial side effects with LTRAs for patients who also have rhinitis or other coexisting conditions involving leukotrienes.
Dahlén and colleagues also pointed out that montelukast does not carry the same risk for systemic adverse events as glucocorticoids, such as the inhibition of bone growth in children, and may be a more affordable option as generic versions will soon be available.