Step-off Approach to LABA Therapy May Prove Risky, Study Finds

According to an Archives of Internal Medicine study published online Aug. 27, stopping long-acting beta-2 agonist (LABA) therapy in adults and older children who have asthma controlled by a combination of LABAs and inhaled corticosteroids (ICSs) results in increased asthma-related impairment.

The study's findings clash with an FDA drug safety communication issued in February 2010 that recommends LABAs "be used for the shortest duration of time required to achieve control of asthma symptoms and discontinued, if possible, once asthma control is achieved."

The study, a meta-analysis that looked at five randomized controlled trials involving discontinuation of combination LABA/ICS therapy in patients with asthma, found that available data suggest that an LABA step-off approach increases the risk of loss of asthma control in adults. The study cautioned, however, that uncertainty exists regarding estimated effects "because of the risk of bias in the included studies, imprecision of the estimates and indirectness of the evidence."

In April 2011, the FDA mandated that LABA manufacturers conduct five randomized, double-blind, controlled clinical trials directly comparing the addition of LABAs to ISC therapy versus use of ISCs alone, but those results are not expected until 2017.

According to the study authors, there were no statistically significant benefits seen with use of the LABA step-off approach compared with continued combination therapy, and step-off therapy was shown to reduce patient quality-of-life scores and asthma control, among other negatives.

"Discontinuation of LABAs also increased symptom frequency … and the risk of withdrawing from the study because of lack of efficacy or loss of asthma control," the authors wrote. "Patients who discontinued LABAs required a mean of 0.71 more puffs per day of a rescue bronchodilator."

Although few new data regarding the safety of LABAs are surfacing, the study pointed out that data from existing trials have led to contradictory conclusions that leave clinicians in the unsettling role of trying to decide how to step down LABA therapy appropriately.

"Indeed, the present study was prompted by members of the American Academy of Allergy, Asthma and Immunology and American Thoracic Society appealing to the leadership of these professional societies for guidance, especially in regard to how best to step down asthma treatment once asthma is controlled," the authors wrote.

The authors concluded by calling for studies that include a comparison between LABA step-off therapy and decreasing the dose of ICSs. They also suggested that such studies be conducted in a variety of populations because patients with differing levels of asthma severity could respond differently.

"Until those data are available, physicians need to evaluate the risk-benefit ratio of LABAs for their individual patients," the authors wrote. "Results of this review and many previous studies support the positive effects of LABAs for achieving and maintaining asthma control."