DALLAS — As-needed treatment with a combination of the inhaled corticosteroid budesonide and the long-acting bronchodilator formoterol (Symbicort) outperformed as-needed albuterol and was on par with budesonide maintenance for the prevention of asthma exacerbations in adults with mild asthma, according to new research.
Patients assigned budesonide-formoterol had fewer annual exacerbations compared with those on albuterol (RR 0.49, 95% CI 0.33-0.72, P<0.001), reported Richard Beasley, DSc, of the Medical Research Institute of New Zealand.
And the budesonide-formoterol group’s annual exacerbation rate was not significantly different than that of a budesonide maintenance group (RR 1.12, 95% CI 0.70-1.79, P=0.65), according to the presentation at the American Thoracic Society annual meeting here.
Results from the 52-week, open-label Novel START trial, which was designed to mimic real-world, clinical use were published simultaneously in the New England Journal of Medicine.
U.S. and international guidelines recommend the use of short-acting β2-agonists (SABAs) as needed for the treatment of mild intermittent asthma, with maintenance inhaled corticosteroid added when symptoms become persistent. But compliance with maintenance therapy in patients with mild asthma is notoriously poor, with patients tending to rely more on rescue inhalers for symptom relief.
Two recent randomized, double-blind, controlled trials of the budesonide-formoterol inhaled treatment Symbicort (SYGMA 1 and SYGMA 2) showed budesonide-formoterol to be as effective as budesonide maintenance treatment for the prevention of exacerbations.
In an interview with MedPage Today, pediatric pulmonary specialist Andrew Bush, MD, of Imperial College London, who was not involved with the study, called Novel START, as well as SYGMA 1 and SYGMA 2, “very important research that should alter guidelines quickly.”
“We have completely failed to sell patients with mild asthma on the idea of taking regular twice-daily medication whether they need it or not [for symptoms],” he said, adding that the paper shows that starting therapy with a steroid and long-acting beta agonist therapy taken as needed works well without the use of maintenance medication.
The 52-week Novel START trial randomized 675 adults with mild intermittent and persistent asthma to one of three groups:
- Albuterol group: albuterol (100 μg delivered in two inhalations from a pressurized metered-dose inhaler as needed for asthma symptoms)
- Budesonide maintenance group: budesonide (200 μg, one inhalation through a Turbuhaler twice daily) plus as-needed albuterol
- Budesonide-formoterol group: 200 μg of budesonide and 6 μg of formoterol, one inhalation through a Turbuhaler as needed
Absolute rates of annual exacerbations per patient were 0.400 in the albuterol group, 0.175 in the budesonide maintenance group, and 0.195 in the budesonide-formoterol group. For the secondary endpoint of severe exacerbations, the 9 in the budesonide-formoterol group were significantly fewer than the 23 in the albuterol group (RR 0.40, 95% CI 0.18-0.86) and 21 in the budesonide maintenance group (RR 0.44, 95% CI 0.20-0.96).
Maintenance treatment with budesonide was more efficacious in this population for control of asthma symptoms, “which suggests that for the patient for whom asthma symptoms rather than exacerbations are the most bothersome, maintenance treatment has value,” the researchers noted.
In an accompanying editorial, Gary W.K. Wong, MD, of the Chinese University of Hong Kong, wrote that the trial results, together with those from SYGMA 1 and 2, “provide convincing evidence that budesonide-formoterol used as needed is an acceptable alternative to maintenance budesonide maintenance therapy for patients with mild asthma.”
Wong added that the trial and the SIENA study, also presented at ATS 2019, showed that treatment with as-needed SABA alone is associated with an increased risk for exacerbations.
“Replacement of as-needed SABA treatment with as-needed budesonide-formoterol or inhaled glucocorticoid maintenance therapy could reduce such risk by approximately 50%,” Wong wrote.
Bush told MedPage Today that the common practice of relying on a SABA alone is not only risky – it can be deadly.
He cited the case of a 19-year-old woman in the U.K. who recently died following an asthma attack. It turned out that during the previous year she had filled prescriptions for steroid inhalers only twice, but had used 19 canisters of albuterol.
“This is not uncommon,” Bush said. “Many, many asthma deaths occur among patients who just rely on more and more albuterol.”
The Novel START trial was funded by AstraZeneca and the Health Research Counsel of New Zealand.
Beasley reported receiving personal fees and non-financial support from AstraZeneca and Theravance Biopharma.
Wong is employed by the New England Journal of Medicine as an associate editor.