Budesonide–formoterol bests albuterol for exacerbations in adults with mild asthma
Budesonide–formoterol demonstrates superiority over albuterol, when used on an as-needed treatment basis, for preventing exacerbations in adult patients with mild asthma, according to the results of the open-label Novel START trial.
The analysis included 675 of 668 patients who underwent randomization to 52 weeks of treatment with one of the following: albuterol (100 μg, two inhalations as needed; n=223), budesonide (200 μg, one inhalation twice daily) plus as-needed albuterol (budesonide maintenance group, n=225), or budesonide–formoterol (200 μg of budesonide and 6 μg of formoterol, one inhalation as needed; n=220).
Annualized rate of asthma exacerbations, the primary study outcome, was lower in the budesonide–formoterol vs albuterol group (absolute rate, 0.195 vs 0.400; relative rate, 0.49, 95 percent CI, 0.33–0.72; p<0.001) and did not differ significantly between the budesonide–formoterol and budesonide maintenance groups (absolute rate, 0.195 vs 0.175; relative rate, 1.12, 0.70–1.79; p=0.65). [N Engl J Med 2019;380:2020-2030]
Furthermore, severe exacerbations occurred less frequently in the budesonide–formoterol group than in both the albuterol group (9 vs 23; relative risk, 0.40, 0.18–0.86) and the budesonide maintenance group (9 vs 21; relative risk, 0.44, 0.20–0.96).
Mean daily dose of inhaled budesonide was 107 μg in the budesonide–formoterol group and 222 μg in the budesonide maintenance group.
“The incidence and type of adverse events (AEs) reported were consistent with those in previous trials and with reports in clinical use,” the investigators noted.
Any AEs occurred in 81.9 percent of patients in the albuterol group, 83.7 percent in the budesonide maintenance group and 78.4 percent in the budesonide–formoterol group. The most common AEs were upper respiratory tract infection, nasopharyngitis, asthma and influenza.
“Th[e] finding suggests that the use of an inhaled glucocorticoid in the situation of worsening asthma as perceived by the patient, through the vehicle of a co-administered bronchodilator (such as formoterol) used on an as-needed basis, may reduce the risk of the exacerbation becoming severe enough for the patient to seek urgent care,” the investigators said.
“However, maintenance treatment with budesonide [i]s superior 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,” they added.
The investigators also pointed out that the current trial extends the results of the double-blind, double-dummy Symbicort Given as Needed in Mild Asthma (SYGMA) trials to an open-label treatment regimen that reflects real-world practice. [N Engl J Med 2018;378:1865-1876; N Engl J Med 2018;378:1877-1887]
“Our population had less severe asthma than the patients in the SYGMA trials, given that the patients in our trial were taking only a short-acting beta agonist (SABA) at enrolment and approximately half reported using a SABA on an average of two or fewer occasions per week at enrolment… As a result, our trial extends the evidence for the efficacy of as-needed use of budesonide–formoterol to a level at which initiation of inhaled glucocorticoid therapy is recommended by the Global Initiative for Asthma for risk reduction—although the therapy is often not prescribed or taken,” they explained. [http://www.ginasthma.org/]
In an accompanying editorial, Dr Gary W.K. Wong from the Chinese University of Hong Kong–Prince of Wales Hospital commented that the data from Novel START, along with those from the SYGMA trials, “provide convincing evidence that budesonide–formoterol used as needed is an acceptable alternative to maintenance budesonide therapy for patients with mild asthma.” [N Engl J Med 2019;380:2064-2066]
“[W]e 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,” Wong added.