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Among patients with mild asthma, as-needed use of a fixed-dose inhaler combining budesonide and formoterol (Symbicort) proved effective for preventing exacerbations and loss of lung function, but the treatment was less effective than maintenance therapy for controlling symptoms, according to results from two international trials.

Findings suggest that treating asthma patients with the combination inhaler on an as-needed basis represents a potential alternative to daily maintenance therapy with an inhaled corticosteroid (ICS) alone or in combination with a long-acting beta agonist (LABA).

As-needed treatment with the ICS-LABA fixed-dose therapy should deliver lower steroid doses than maintenance therapy, potentially leading to fewer steroid-related side effects and reduced treatment costs for patients with mild asthma, the researchers said.

The two studies were published May 16 in the , and are scheduled to be presented this weekend at the American Thoracic Society's annual conference.

Both trials were sponsored by Symbicort's manufacturer, AstraZeneca. The fixed-dose therapy is approved for the maintenance treatment of asthma patients age 6 and older who are not adequately controlled with an ICS or an ICS plus LABA.

Michael Wechsler, MD, of National Jewish Health in Denver, who was not involved with the studies, told MedPage Today that as-needed therapy has many potential advantages over daily maintenance treatment for patients with mild asthma.

"The downside of as-needed treatment appears to be somewhat less asthma control, but that has to be balanced against the potential benefits, including not having to take maintenance medication every day, the lower costs, and the potentially lower side effects from steroids," he explained.

The lead researcher of one of the new studies, Paul O'Bryne, MD, of McMaster University in Ontario, said that taking treatment adherence out of the equation is a major benefit. "If all patients used their inhaled steroids as prescribed we wouldn't really need this," he told MedPage Today. "But we know that they don't. Due to concerns about side effects -- which I think are largely misplaced -- as well as other reasons people don't adhere to regular medications, the maintenance option is never going to be truly viable."

The 52-week by his group was designed to compare as-needed budesonide-formoterol with a conventional rescue medication, the short-acting beta agonist terbutaline, as well as budesonide used as daily maintenance.

The study involved 3,836 patients ages 12 and older with mild asthma randomly assigned to receive one of three treatment regimens:

• Twice daily placebo plus the terbutaline (0.5 mg) used as needed (terbutaline group)
• Twice-daily placebo plus budesonide-formoterol (200 μg of budesonide and 6 μg of formoterol) used as needed (budesonide-formoterol group)
• Twice-daily budesonide (200 μg) plus terbutaline used as needed (budesonide maintenance group)

Budesonide-formoterol was found to be superior to terbutaline with respect to the mean percentage of weeks with well-controlled asthma per patient, (34.4% versus 31.1% of weeks; odds ratio, 1.14; 95% CI, 1.00-1.30; P=0.046, but inferior to budesonide maintenance therapy (34.4% and 44.4%, respectively; odds ratio, 0.64; 95% CI, 0.57 to 0.73).

Among the other findings:

• The annual rate of severe exacerbations was 0.20 with terbutaline, 0.07 with budesonide-formoterol, and 0.09 with budesonide maintenance therapy; rate ratio, 0.36 (95% CI 0.27-0.49) for budesonide-formoterol versus terbutaline and 0.83 (95% CI 0.59 to 1.16) for budesonide-formoterol versus budesonide maintenance therapy
• The rate of adherence in the budesonide maintenance group was 78.9%
• The median metered daily dose of inhaled glucocorticoid in the budesonide-formoterol group (57 μg) was 17% of the budesonide maintenance group (340 μg)

The trial results suggest that budesonide-formoterol used as needed is superior to terbutaline, inferior to budesonide maintenance therapy for controlling asthma symptoms, and similar to budesonide maintenance therapy for reducing exacerbations with a much lower glucocorticoid load, the researchers noted.

In the 52-week , comparing as-needed budesonide-formoterol with budesonide maintenance treatment in patient with mild asthma, 2,089 patients were randomized to receive as-needed budesonide-formoterol and 2,087 received budesonide maintenance therapy.

The study, led by Eric D. Bateman, MD, of the University of Cape Town in South Africa, showed that budesonide-formoterol used as needed was noninferior to budesonide maintenance therapy for severe exacerbations; the annualized rate of severe exacerbations was 0.11 (95% CI 0.10-0.13) and 0.12 (95% CI 0.10-0.14), respectively (rate ratio 0.97; upper one-sided 95% confidence limit, 1.16).

The median daily metered dose of inhaled glucocorticoid was lower in the budesonide-formoterol group (66 μg) than in the budesonide maintenance group (267 μg).

The time to the first exacerbation was similar in the two groups (hazard ratio 0.96; 95% CI 0.78-1.17). The change in Asthma Control Questionnaire-5 score showed a difference of 0.11 units (95% CI 0.07-0.15) in favor of budesonide maintenance therapy.

In an published with the two studies, Stephen Lazarus, MD, of the University of California San Francisco, noted that the median daily dose of inhaled glucocorticoid steroid in the study patients receiving the fixed-dose ICS-LABA treatment was 17% to 25% of that in the groups randomized to maintenance therapy.

"Not only does this reduce the potential for glucocorticoid side effects and improve the acceptability of the treatment regimen to glucocorticoid-averse patients, but it also has the potential to reduce costs dramatically," Lazarus wrote.

"Assuming that approximately 18.4 million adults in the United States have asthma, that 65% of these have persistent asthma and 50% to 75% of those cases are mild, and that the average cost of a glucocorticoid inhaler is $218 per month, the savings in drug costs in the United States alone would be close to $1 billion per year."