DALLAS — Treatment with the inhaled glucocorticoid mometasone or the long-acting muscarinic antagonist tiotropium resulted in similar outcomes among the majority of patients with mild asthma and low (less than 2%) eosinophil levels enrolled in the SIENA trial.
No significant differences were seen in response to either of the drugs when compared with placebo in the randomized, double-blind, placebo controlled crossover study. The findings were presented here at the annual meeting of the American Thoracic Society and published simultaneously in the New England Journal of Medicine.
Treatment guidelines in the U.S. and internationally recommend the use of short-acting β2-agonists (SABAs) as needed for mild, intermittent asthma, with inhaled glucocorticoid maintenance treatment added when symptoms become persistent.
But asthma patients with low eosinophil counts, which includes roughly half of patients with mild persistent asthma, often exhibit poor response to treatment with inhaled glucocorticoids. Despite this, treatment guidelines recommend the therapy for all patients with persistent asthma.
The SIENA researchers, Stephen Lazarus, MD, of the University of California San Francisco, and colleagues, enrolled 295 patients with mild asthma who were at least age 12. Their asthma was categorized by eosinophil count (less than 2% or 2% or more); 73% had low eosinophil levels (less than 2%), and 59% of these patients had a differential response to treatment.
"Among the patients with a low eosinophil level who had a differential treatment response, 57% (95% CI, 48-66) had a better response to mometasone, and 43% (95% CI, 34-52) had a better response to placebo (P=0.14)," the team wrote. "In contrast, 60% (95% CI, 51-68) had a better response to tiotropium, and 40% (95% CI, 32-49) had a better response to placebo (P=0.029)."
Response to mometasone was significantly better than placebo response among patients in the higher eosinophil group (74% vs 26%), but response to tiotropium was not significantly better (57% vs 43%).
The findings suggest that current guidelines should be "reevaluated for patients with mild, persistent asthma for whom evidence of type 2 inflammation is lacking," Lazarus and co-authors stated.
Although the patients in the study had mild asthma, their symptoms were sufficient to meet the criteria for maintenance glucocorticoid treatment, the researchers noted.
"Among such patients, adherence to prescribed regimens is often lacking because they tend to stop using inhaled glucocorticoids when they feel well, they have concern about potential adverse effects, or they perceive that the treatment is ineffective. Although our data for patients in the low-eosinophil stratum do not support current treatment recommendations, the appropriate controller treatment for these patients remains to be determined," the researchers wrote.
They concluded that the findings "provide clinical equipoise for a larger and longer study to compare inhaled glucocorticoids with other treatments for the large number of patients with mild or moderate asthma."
Asked for his perspective, pediatric pulmonary specialist Andrew Bush, MD, of Imperial College London, who was not involved with the study, agreed that larger trials are needed to better understand the role of inhaled glucocorticoids in the treatment of mild asthma.
He told MedPage Today that while the evidence that the therapy may not be efficacious in non-eosinophilic asthma is mounting, it is too soon to base treatment decisions on a patient’s eosinophil count.
"The gospel has been that patients with asthma need inhaled steroids — end of discussion," Bush said. "This study adds to the evidence that this might not be the case, but it is still proof of concept. There is not enough evidence to say you can junk inhaled steroids in this group, but there is enough to warrant a definitive trial to determine if we can do that."
In an editorial commenting on the study, Gary W.K. Wong, MD, of the Chinese University of Hong Kong, said that biomarker-guided therapies are likely to play a large role in the management of mild, persistent asthma in the future.
"Larger trials with adequate power to detect all important asthma outcomes are needed to evaluate whether LAMAs would be an effective alternative for the treatment of persistent asthma in patients who do not have eosinophilic airway inflammation," Wong wrote.
The SIENA trial was funded by the National Heart, Lung, and Blood Institute.
Lazarus reported having no relevant relationships with industry related to the study.