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LOUISVILLE, Ky. -- An investigational fixed-dose combination of a short-acting beta₂-adrenergic agonist and an inhaled corticosteroid appeared to slow the deterioration in lung function and reduce severe exacerbations for patients with mild-to-moderate asthma, according to an exploratory analysis of a phase III trial.

Among the nearly 1,000 patients in the DENALI trial, those in the albuterol-budesonide groups had numerically fewer asthma deteriorations over 12 weeks when compared with either the albuterol monotherapy or placebo groups (0.8-0.9 vs 1.4-1.6 per patient, respectively), said Bradley Chipps, MD, of Capital Allergy & Respiratory Disease Center in Sacramento, California.

And over this study period, the proportion of patients experiencing at least one severe exacerbation was lower in the high-dose albuterol-budesonide group (2%), the budesonide monotherapy group (2%), and the low-dose albuterol-budesonide group (2.5%), when compared with the placebo and albuterol-alone groups (7.1% and 10.2%).

The combination of albuterol-budesonide is being developed as an as-needed treatment for asthma, but the constraints of the clinical trial required a four-times-a-day treatment protocol, he said in a presentation at the American College of Allergy, Asthma & Immunology (ACAAI) annual meeting.

Chipps noted that DENALI was designed to fulfill the FDA Combination Rule to confirm that both elements of the combination contributed to lung-function efficacy -- which was accomplished. The current study sought to look specifically at whether the combination product had a favorable effect on the exploratory objectives of preventing deterioration and severe asthma exacerbations.

ACAAI session moderator and meeting program chair Brian Kelly, MD, of Midwest Allergy and Asthma Clinic in Omaha, Nebraska, told MedPage Today that the findings were "a potential game-changer."

"The DENALI study suggests that having an inhaled corticosteroid with a combined short-acting beta agonist shows a significant potential benefit for patients over the monotherapy alone," he said. "Patients may be able to use this combination as needed more so than with albuterol. It is not yet available, but it is something we are waiting for."

The mean age of the 989 patients included in the DENALI analysis was 48-50 years across the five study arms, Chipps reported, and about 60% of the participants were women. Just under half had a background history of taking inhaled corticosteroids. The mean number of rescue medication needed daily was 2.5 to 2.9 inhalations across the study groups.

Overall, 197 patients received the high-dose (180 µg/160 µg) albuterol-budesonide combination four times daily, while 201 received the low-dose (180 µg/80 µg) albuterol-budesonide combination, 196 received albuterol monotherapy (180 µg), 199 received budesonide monotherapy (160 µg), and 196 received placebo.

Asthma deterioration was defined as one or more of the following conditions that lasted at least 2 consecutive days: 20% or greater decline in lung function tests, need for albuterol at four puffs a day and use that was at least two puffs greater than baseline, and increases in nighttime and daytime symptoms scores. One or more episodes occurred in 34.5% of patients in the high-dose combination arm, in 42.3% of the low-dose combination group, in 58.7% on albuterol monotherapy, in 47.7% on budesonide monotherapy, and in 53.6% of those on placebo.

Severe asthma exacerbations were defined as one of the following: need for a 2-3 day course of oral corticosteroids or a corresponding injected dose of steroids; an emergency department or urgent care visit due to asthma that required systemic corticosteroids; or hospitalization due to asthma. With the high-dose combination, severe exacerbations occurred in five patients (totaling 22 days), while five patients in the low-dose combination had severe exacerbations (31 days). In the monotherapy arms, severe exacerbations occurred in 23 patients on albuterol (130 days) and five patients on budesonide (42 days). Sixteen patients on placebo had severe exacerbations (totalling 85 days)

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