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Single maintenance and reliever therapy using an inhaled corticosteroid (ICS) and the long-acting β₂-agonist formoterol was associated with a significantly lower risk for asthma exacerbations compared to separate ICS control and rescue with a short-acting β2-agonist, researchers reported.

In a review of 16 randomized randomized clinical trials, the therapeutic strategy known as SMART resulted in significantly fewer asthma attacks, hospitalizations and emergency department visits in patients age 12 years and older with persistent asthma, compared to use of the standard care treatment of using separate medications for asthma control and rescue.

The meta-analysis was part of a larger review of asthma therapies requested by the National Heart, Lung and Blood Institute for the federal Agency for Healthcare Research and Quality (AHRQ).

Diana Sobieraj, PharmD, of the University of Connecticut, and colleagues, reported the findings in , along with findings from a separate analysis examining the use of long-acting muscarinic antagonists (LAMA) as an ICS add on therapy.

It has been 11 years since asthma guidelines in the U.S. were last updated by the National Asthma Education and Prevention Program, and those guidelines call for stepped approach to asthma pharmacotherapy. They also were issued before the availability of LAMA treatments for asthma.

In the review of SMART trials, which included roughly 22,500 patients (mean age 42), the strategy was associated with a reduced risk of asthma exacerbations compared with the same dose of inhaled corticosteroids and LABA as the controller therapy (RR 0.68, 95% CI 0.58-0.80; risk difference −6.4%, 95% CI −10.2% to −2.6%) and a higher dose of inhaled corticosteroids and LABA as the controller therapy (RR 0.77, 95% CI 0.60 to 0.98).

Similar results were seen when SMART was compared with inhaled corticosteroids alone as the controller therapy.

"We found that the combined use of inhaled corticosteroid and LABA as both controller and rescue therapy in patients with persistent asthma who were age 12 and older significantly reduced the risk of asthma exacerbations compared to traditional ICS and LABA with albuterol used as rescue medication," Sobieraj told 番茄社区app.

The meta-analysis of 15 randomized clinical trials examining LAMA as an add-on treatment to ICS (n=7,122 patients) showed LAMA use to be associated with a significantly lower risk for asthma exacerbations compared to placebo (RR 0.67, 95% CI 0.48-0.92).

When LAMA was compared to LABA as an ICS add-on therapy, no significant reduction in exacerbation risk was seen (RR 0.87, 95% CI 0.53-1.42).

Triple therapy was not significantly associated with a lower risk of exacerbations.

Sobieraj noted that the available evidence suggests no significant difference between LAMAs and LABAs with regard to their impact on asthma exacerbations, asthma symptoms or lung function.

"But the studies we reviewed are not robust enough to determine whether one of these two classes of long-acting bronchodilators may be better than the other," she said.

In an editorial published with the two meta-analyses, Jerry Krishnan, MD, PhD, of the University of Illinois, Chicago; and David Au, MD, of the University of Washington, Seattle, wrote that the findings should inform the update of the 2007 Expert Panel Report 3 (EPR-3) asthma treatment guidelines.

"Updates of EPR-3 are planned, and the results of the meta-analyses of inhaled tiotropium by Sobieraj et al. suggest that LAMA should be offered as a treatment option in steps 3 through 6 in the updated guidelines," they wrote.

"Such changes to the EPR-3 guidelines would help to harmonize the approval by the FDA for inhaled tiotropium and the clinical guidelines in the United States. For patients and clinicians, the results from these meta-analyses suggest that dual therapy with scheduled doses of inhaled corticosteroids and LABA or inhaled corticosteroids and LAMA should help reduce the risk of future asthma exacerbations in patients with inadequate asthma control when using inhaled corticosteroids alone."