Boxed Warning Removed for Asthma-Related Deaths from Combination Inhaled Treatment

The FDA recently removed a Boxed Warning for combination therapies of long-acting beta agonists (LABAs) and inhaled corticosteroids (ICS) related to the risk of asthma-related deaths, according to a press release.

The elimination of the warning resulted from a review of 4 large clinical trials that demonstrated treating asthma with LABAs plus ICS may not increase asthma-related adverse events compared with ICS monotherapy, according to the FDA. The description of the studies will now be included in the prescribing information for these drugs.

The studies also showed that LABA/ICS combination therapy did not substantially increase the risk of asthma-related hospitalizations, intubation, or asthma-related mortality compared with ICS monotherapy, according to the release.

In 2011, the FDA required manufacturers of fixed-dose combination drugs, including a LABA and an ICS, to conduct a large 26-week trial to determine the risk of asthma-related events from the therapy. These trials included 41,297 patients.

The primary efficacy endpoint was asthma exacerbation, defined as worsening of the condition and requiring the use of systemic corticosteroids for 3 or more days, or in-patient hospitalization or emergency department use due to asthma.

The results of subgroup analyses for gender, adolescents (aged 12 to 18 years), and African Americans were consistent with the primary analysis, according to the FDA.

The investigators also reported that the LABA/ICS combination reduced asthma exacerbations compared with ICS monotherapy.

Due to the new findings, the FDA is recommending that health care professionals reference the newly-approved drug labels for LABA/ICS combination drugs. They also advise patients and caregivers to discuss the treatment if there are concerns, but they should not stop taking asthma drugs without consulting a health care professional, according to the release.