In the Journals

Budesonide-formoterol reliever therapy outperforms maintenance plus as-needed therapy for preventing asthma exacerbations

Richard Beasley
Richard Beasley

Data from the PRACTICAL study showed that budesonide-formoterol reliever therapy in a single inhaler for patients with mild to moderate asthma was associated with a 31% reduction in the risk for severe exacerbations, as compared with maintenance budesonide plus terbutaline reliever therapy.

“The budesonide-formoterol reliever regimen in mild to moderate asthma is based on the proven efficacy of the budesonide-formoterol maintenance and reliever regimen in moderate to severe asthma,” Richard Beasley, DSc, from the Medical Research Institute of New Zealand and the Capital and Coast District Health Board, wrote in an email to Healio Pulmonology. “This regimen has the potential to overcome the problem of underuse of inhaled steroids in asthma by using the reliever as its vehicle for administration.”

Investigators conducted the open-label, parallel-group, superiority trial at 15 primary care or hospital-based clinical trial units and primary care practices in New Zealand. They randomly assigned 890 adults aged 18 to 75 years with asthma to reliever therapy with one inhalation of budesonide 200 g–formoterol 6 g (Symbicort Turbuhaler, AstraZeneca) as needed or maintenance budesonide 200 g (Pulmicort Turbuhaler, AstraZeneca) twice daily plus two inhalations of terbutaline 250 g (Bricanyl Turbuhaler, AstraZeneca; not available in the U.S.) as needed.

All patients were using short-acting beta-agonists for symptom relief with or without maintenance low to moderate doses of inhaled corticosteroids during the previous 12 weeks. The study included six visits over 52 weeks and the primary outcome was the number of severe exacerbations per patient per year.

Fewer exacerbations

The final analysis included 885 patients. Results showed that the rate of severe asthma exacerbations was lower in the as-needed budesonide-formoterol group than in the maintenance budesonide plus as-needed terbutaline group (relative rate = 0.69; 95% CI, 0.48-1), as was the rate of combined moderate and severe asthma exacerbations (relative rate = 0.7; 95% CI, 0.51-0.95). Both time to first severe exacerbation and time to first moderate or severe exacerbation were longer with budesonide-formoterol vs. maintenance budesonide plus as-needed terbutaline, the researchers noted.

The most common adverse event in both treatment groups was nasopharyngitis, occurring in 35% of patients receiving as-needed budesonide-formoterol and 32% of those receiving maintenance budesonide plus as-needed terbutaline.

“This is the first independent study showing that budesonide-formoterol reliever therapy outperforms maintenance inhaled corticosteroid and [short-acting beta-agonist (SABA)] reliever therapy in mild to moderate asthma in reducing severe exacerbation risk,” Beasley said. “Taken together with the three earlier studies of budesonide-formoterol reliever therapy in mild asthma published in The New England Journal of Medicine, and the studies of the budesonide-formoterol maintenance and reliever regimen in moderate to severe asthma, there is now strong evidence that budesonide-formoterol outperforms SABA therapy across the spectrum of asthma severity.”

The next step, he added, is to examine the regimen in children with asthma.

Lingering questions

In a linked comment, Marc Gauthier, MD, and Sally E. Wenzel, MD, both from the department of medicine at the University of Pittsburgh Graduate School of Public Health, noted that the findings are in keeping with those of previous trials, but questions remain, including whether the inhaled corticosteroid component adds benefit for patients with mild asthma without eosinophilic inflammation. They also said that it is undetermined “how mild is mild enough” in terms of asthma for as-needed inhaled corticosteroid-beta-agonist therapy to be beneficial.

Further research into which patients would benefit from this treatment and which would fare better with maintenance therapy is also necessary, according to Gauthier and Wenzel.

“Although the higher cost of combination therapies compared with SABA inhalers in some countries (including the USA) might reduce adoption of the as-needed inhaled corticosteroid-beta-agonist regimen, this combination could modestly improve asthma outcomes over daily maintenance therapy, reduce overall inhaled corticosteroid burden, and possibly improve patient satisfaction, making it a very PRACTICAL option,” they wrote. – by Melissa Foster

Disclosures: The Health Research Council of New Zealand funded this study. Beasley reports he has received grants from AstraZeneca, Genentech and GlaxoSmithKline; and he has received personal fees from AstraZeneca and Theravance. Please see the study for all other authors’ relevant financial disclosures.

Richard Beasley
Richard Beasley

Data from the PRACTICAL study showed that budesonide-formoterol reliever therapy in a single inhaler for patients with mild to moderate asthma was associated with a 31% reduction in the risk for severe exacerbations, as compared with maintenance budesonide plus terbutaline reliever therapy.

“The budesonide-formoterol reliever regimen in mild to moderate asthma is based on the proven efficacy of the budesonide-formoterol maintenance and reliever regimen in moderate to severe asthma,” Richard Beasley, DSc, from the Medical Research Institute of New Zealand and the Capital and Coast District Health Board, wrote in an email to Healio Pulmonology. “This regimen has the potential to overcome the problem of underuse of inhaled steroids in asthma by using the reliever as its vehicle for administration.”

Investigators conducted the open-label, parallel-group, superiority trial at 15 primary care or hospital-based clinical trial units and primary care practices in New Zealand. They randomly assigned 890 adults aged 18 to 75 years with asthma to reliever therapy with one inhalation of budesonide 200 g–formoterol 6 g (Symbicort Turbuhaler, AstraZeneca) as needed or maintenance budesonide 200 g (Pulmicort Turbuhaler, AstraZeneca) twice daily plus two inhalations of terbutaline 250 g (Bricanyl Turbuhaler, AstraZeneca; not available in the U.S.) as needed.

All patients were using short-acting beta-agonists for symptom relief with or without maintenance low to moderate doses of inhaled corticosteroids during the previous 12 weeks. The study included six visits over 52 weeks and the primary outcome was the number of severe exacerbations per patient per year.

Fewer exacerbations

The final analysis included 885 patients. Results showed that the rate of severe asthma exacerbations was lower in the as-needed budesonide-formoterol group than in the maintenance budesonide plus as-needed terbutaline group (relative rate = 0.69; 95% CI, 0.48-1), as was the rate of combined moderate and severe asthma exacerbations (relative rate = 0.7; 95% CI, 0.51-0.95). Both time to first severe exacerbation and time to first moderate or severe exacerbation were longer with budesonide-formoterol vs. maintenance budesonide plus as-needed terbutaline, the researchers noted.

The most common adverse event in both treatment groups was nasopharyngitis, occurring in 35% of patients receiving as-needed budesonide-formoterol and 32% of those receiving maintenance budesonide plus as-needed terbutaline.

“This is the first independent study showing that budesonide-formoterol reliever therapy outperforms maintenance inhaled corticosteroid and [short-acting beta-agonist (SABA)] reliever therapy in mild to moderate asthma in reducing severe exacerbation risk,” Beasley said. “Taken together with the three earlier studies of budesonide-formoterol reliever therapy in mild asthma published in The New England Journal of Medicine, and the studies of the budesonide-formoterol maintenance and reliever regimen in moderate to severe asthma, there is now strong evidence that budesonide-formoterol outperforms SABA therapy across the spectrum of asthma severity.”

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The next step, he added, is to examine the regimen in children with asthma.

Lingering questions

In a linked comment, Marc Gauthier, MD, and Sally E. Wenzel, MD, both from the department of medicine at the University of Pittsburgh Graduate School of Public Health, noted that the findings are in keeping with those of previous trials, but questions remain, including whether the inhaled corticosteroid component adds benefit for patients with mild asthma without eosinophilic inflammation. They also said that it is undetermined “how mild is mild enough” in terms of asthma for as-needed inhaled corticosteroid-beta-agonist therapy to be beneficial.

Further research into which patients would benefit from this treatment and which would fare better with maintenance therapy is also necessary, according to Gauthier and Wenzel.

“Although the higher cost of combination therapies compared with SABA inhalers in some countries (including the USA) might reduce adoption of the as-needed inhaled corticosteroid-beta-agonist regimen, this combination could modestly improve asthma outcomes over daily maintenance therapy, reduce overall inhaled corticosteroid burden, and possibly improve patient satisfaction, making it a very PRACTICAL option,” they wrote. – by Melissa Foster

Disclosures: The Health Research Council of New Zealand funded this study. Beasley reports he has received grants from AstraZeneca, Genentech and GlaxoSmithKline; and he has received personal fees from AstraZeneca and Theravance. Please see the study for all other authors’ relevant financial disclosures.