Combination ICS/LABA inhalers safe to use for asthma, study confirms

Findings support FDA’s removal of black box warning for ICS/LABA combination inhalers

Combination inhalers containing a long-acting beta-2 agonist (LABA) and an inhaled corticosteroid (ICS) can be safely used to treat asthma without increased safety concerns, a team of international researchers reported. Their  provide strong support for FDA’s removal of the black box warning for ICS/LABA combination inhalers in December 2017.

“This study—of over 36,000 patients—provided very conclusive evidence that the use of long-acting beta-2 agonists, in conjunction with inhaled corticosteroids, is safe,” said lead author William W. Busse, MD, of the University of Wisconsin School of Medicine and Public Health.

The results are “very positive, very reassuring,” Busse said, “to the point where the FDA has removed the black box warning.” He added that this is a “very unusual event for them.”  

Sally M. Seymour, MD, and colleagues from FDA agree that this is a rare step. “The removal of a boxed warning from a product label is not a common occurrence, but the evidence in this instance was decisive,” they wrote in a accompanying Busse’s study.

FDA first required black box warnings on LABA inhalers in 2003, given research suggesting an increased risk of hospitalizations, intubations, and death associated with their use in asthma treatment. At that time, ICS/LABA inhalers were not widely used, but when combination therapy became the standard of care, it was unknown whether the ICS component would alleviate safety concerns. Consequently, in 2011, FDA required AstraZeneca, GlaxoSmithKline, Merck, and Novartis—the four pharmaceutical companies promoting ICS/LABA inhalers for asthma treatment—to perform clinical trials evaluating the safety of combination therapy versus ICS monotherapy. Busse and his team, all members of an independent joint oversight committee, conducted a combined analysis of these trials’ results.  

They found 3 asthma-related intubations and 2 asthma-related deaths among 4 of the 36,010 patients studied. Two of the intubations occurred in the monotherapy group, while the two deaths and third intubation occurred in the combination therapy group. When Busse and his team looked at serious asthma-related events as a composite of intubation, hospitalization, or death, they found similar results in both groups. However, asthma exacerbations were more common in the monotherapy group than in the combination therapy group (11.7% vs. 9.8%, P < 0.001). Combination ICS/LABA therapy was associated with a 17% lower risk of exacerbation than therapy with an ICS alone, findings indicated. 

They concluded that their findings supported both the Global Initiative for Asthma and the Expert Panel Report 3 (EPR-3) treatment guidelines in their recommendation of combination ICS/LABA therapy for asthma management. 

The results did not suggest that LABAs can ever be safely used as monotherapy in asthma patients, however. “They must always be used in combination with an inhaled corticosteroid,” Busse said. 

 For the full article, please visit for the September 2018 issue of Pharmacy Today.