Albuterol-budesonide decreases asthma deteriorations, exacerbations

LOUISVILLE, Ky. — Patients treated with albuterol and budesonide experienced less asthma deteriorations and exacerbations over 12 weeks compared with patients who received the mono-components or placebo, according to DENALI study results.

These results were presented at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting.

“As asthma symptoms worsen, patients typically rely on short-acting beta antagonists as rescue therapy; however, short-acting rescue therapy provides quick relief from bronchospasm, but fails to address the inflammatory component of the airway that drives airway symptoms in exacerbations,” Bradley E. Chipps, MD, medical director of respiratory therapy and the cystic fibrosis center at Sutter Medical Center, said during his presentation. “A window of opportunity does exist that may be interrupted, stemming rising inflammation and preventing exacerbation, by treating symptoms and the inflammation concomitantly.”

Thus, Chipps and colleagues conducted the phase 3, randomized, 12-week, double-blind multicenter DENALI study to assess a fixed dose of albuterol and budesonide in a single metered-dose inhaler (PT027, Avillion).

As Healio previously reported, the primary analysis of DENALI showed significant benefits in patients with asthma when receiving a fixed-dose combination of albuterol and budesonide at 180/160 µg and 180/80 µg, confirming that both mono-components contributed to the lung function efficacy of albuterol-budesonide.

In an exploratory analysis of the study, Chipps and colleagues assessed data of 989 patients, aged 12 years or older, with mild to moderate asthma to observe how albuterol-budesonide performed against each of its individual components and placebo in terms of asthma deteriorations and severe asthma exacerbations, according to the study abstract.

Researchers randomly assigned 197 patients (mean age, 50 years; 63.5% female) to receive albuterol-budesonide 180/160 µg, 201 patients (mean age, 49.2 years; 63.2% female) to albuterol-budesonide 180/80 µg, 196 patients (mean age, 47.8 years; 60.7% female) to albuterol 180 µg, 199 patients (mean age, 48.3 years; 60.3% female) to budesonide 160 µg and 196 patients (mean age, 49.2 years; 63.3% female) to placebo. Each drug was given four times daily for 12 weeks, in addition to as-needed albuterol sulfate inhalation aerosol (Ventolin HFA, GSK) for asthma symptoms.

“While four-times-a-day dosing does not reflect albuterol-budesonide’s intended real-world as-needed use, DENALI study design required scheduled dosing to evaluate the contributions of both the budesonide and albuterol mono-components in the efficacy of this fixed-drug combination,” Chipps said. “Four-times-a-day dosing also provided the ability to evaluate the safety of regular use over 12 weeks ... at substantially higher doses than is anticipated in the as-needed administration.”

Over 12 weeks, fewer patients receiving both albuterol-budesonide at 180/160 µg (34.5%) and 180/80 µg (42.3%) experienced one or more asthma deterioration compared with the other treatment groups (albuterol, 58.7%; budesonide, 47.7%; placebo, 53.6%).

“The total number of asthma deteriorations was approximately two-fold lower in the albuterol-budesonide high-dose group [at 154] than in the albuterol group [at 320],” Chipps said. “A similar trend was seen with a mean number of asthma deteriorations per patient and the percentage of patients with at least one asthma deterioration.”

Researchers also found that fewer patients receiving either treatment dose of albuterol-budesonide had at least one severe exacerbations during the 12-week treatment period than patients receiving albuterol or placebo (albuterol-budesonide 180/160 µg, 2%; 180/80 µg, 2.5%; albuterol, 10.2%; placebo, 7.1%). Researchers also observed fewer severe exacerbations among patients receiving budesonide alone (2%).

Additionally, patients who received albuterol-budesonide 180/160 µg and 180/80 µg had only 22 and 31 days with exacerbations, whereas those treated with albuterol had 130 days, budesonide had 42 days and placebo had 85 days with exacerbations, according to the abstract.

“DENALI confirmed the contribution of both mono-component in the lung function efficacy of the fixed-dose combination,” Chipps said, adding that the drug is being developed for as-needed use, not four-times-a-day dosing.