A single inhaler containing long-acting beta-2 agonist (LABA) and inhaled corticosteroid (ICS) might be the first step in mild asthma treatment instead of a short-acting beta agonist (SABA) for as-needed reliever therapy, a major study has shown.
Findings from the Novel START trial, presented at the American Thoracic Society (ATS) annual meeting in Dallas, showed that use of a combined formoterol-budesonide (Symbicort) inhaler, taken as needed to relieve symptoms, reduced the risk of asthma exacerbations by 50% compared with use of a salbutamol inhaler alone.
The 12-month study, involving 668 asthma patients in Australia, New Zealand and the UK, also showed that as-needed use of the combined preventer-reliever inhaler reduced severe exacerbations compared with use of salbutamol alone or budesonide maintenance therapy.
However, maintenance treatment with budesonide was superior to as-needed LABA-ICS for control of asthma symptoms.
The 52-week, open-label trial randomised adults with mild asthma to either salbutamol (100μg two inhalations as needed); budesonide (200μg, twice daily via Turbuhaler) plus as-needed salbutamol; or budesonide–formoterol (200μg/6 μg, one inhalation through a Turbuhaler as needed).
The asthma exacerbation rate in the budesonide–formoterol group was about half that of the salbutamol group (absolute rate, 0.195 vs. 0.400; relative rate, 0.49) and not significantly different from the budesonide maintenance group (0.175 RR 1.12)
The number of severe exacerbations was lower for budesonide–formoterol users than for the salbutamol users (9 vs. 23; RR 0.40) and also for the budesonide maintenance group (9 vs. 21; RR 0.44)
In terms of asthma symptoms, ACQ-5 scores were lower in the budesonide–formoterol group than in the salbutamol group (mean difference −0.15) but higher in the budesonide–formoterol group than in the budesonide maintenance group (mean difference,0.14) across the one year study.
“[This] suggests that for the patient for whom asthma symptoms rather than exacerbations are the most bothersome, maintenance treatment has value,” said the authors of the study published simultaneously in the NEJM.
Exposure to corticosteroid was about 50% lower in the budesonide–formoterol group (107μg per day) and compared to the budesonide maintenance group (222 μg)
Study lead investigator Professor Richard Beasley, a respiratory physician and Director of the Medical Research Institute of New Zealand (MRINZ), Wellington, said the results provided new evidence supporting changes in asthma treatment guidelines to favour the use of a single inhaler therapy of LABA-ICS over SABA.
“The trial shows for the first time that when patients take just a single combined preventer-reliever inhaler whenever needed to relieve symptoms, they do a lot better than the current recommended treatment of a regular preventer inhaler taken twice daily plus a reliever inhaler whenever needed to relieve symptoms” he said.
“This novel approach simplifies treatment as it doesn’t require patients to take a preventer inhaler twice daily even when they have no symptoms.”
An accompanying commentary noted that another recent study, the SIENA trial, had shown that many patients with mild intermittent asthma did not have eosinophilic airway inflammation and therefore maintenance budesonide may not be the best therapy for these patients.
“Given all these results, we should carefully review the current guideline recommendations for treating mild asthma. Evidence is building to question the role of as-needed SABAs as the step 1 treatment for mild intermittent asthma,” it said.
The START trial was sponsored by MRINZ, with funding received from AstraZeneca and HRC (NZ).