As-needed budesonide-formoterol a potential game changer for mild asthma

The use of budesonide-formoterol, combined in a single preventer-reliever inhaler, on an as-needed basis more than halves the rate of asthma exacerbations in patients with mild asthma compared with the reliever albuterol used as needed, according to the Novel START* study presented at ATS 2019.

“This novel approach simplifies treatment as it doesn’t require patients to take a preventer inhaler twice daily even when they have no symptoms … With a combined preventer-reliever inhaler, [budesonide-formoterol], patients have more personal and immediate control over their asthma management,” said study lead author Professor Richard Beasley from the Medical Research Institute of New Zealand in Wellington, New Zealand, in an international press release.

“Patients tend to rely on as-needed SABAs** for symptom relief, whereas adherence to inhaled glucocorticoid maintenance therapy is rather poor,” wrote Dr Gary Wong from the Department of Pediatrics at Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, China, in an editorial. [N Engl J Med 2019; 380:2064-2066]. “[Nevertheless,] replacement of as-needed SABA treatment with as-needed budesonide-formoterol or inhaled glucocorticoid maintenance therapy could reduce such risk by approximately 50 percent”.

The researchers conducted an open-label, multicentre, parallel-group trial involving 668 patients with mild asthma (aged 18–75 years) who were previously treated with a SABA therapy for at least two occasions a day. Participants were randomized in a 1:1:1 ratio to receive as-needed albuterol 100 μg (albuterol group, n=223), maintenance budesonide 200 μg plus as-needed albuterol 100 μg (budesonide maintenance group, n=225), or as-needed budesonide 200 μg plus formoterol 6 μg (budesonide-formoterol group, n=220). Date and time of inhaler actuations were recorded by using an electronic inhaler monitoring. Patients were followed up until 52 weeks. [ATS 2019, abstract A7477/P525; N Engl J Med 2019;380:2020-2030]

At 52 weeks, patients who received budesonide-formoterol had a significantly lower rate of asthma exacerbations than those on albuterol alone (absolute rate per patient per year, 0.195 vs 0.400, relative rate [RRate], 0.49, 95 percent confidence interval [CI], 0.33–0.72; p<0.001).

Both the budesonide-formoterol and maintenance budesonide groups showed similar rates of asthma exacerbation (absolute rate per patient per year, 0.195 vs 0.175, RRate, 1.12, 95 percent CI, 0.70–1.79; p=0.65).

However, a lower number of severe exacerbations was observed among patients on as-needed budesonide-formoterol than those on maintenance budesonide (9 vs 21, relative risk [RRisk], 0.44, 95 percent CI, 0.20–0.96) or albuterol alone (9 vs 23, RRisk, 0.40, 95 percent CI, 0.18–0.86), suggesting that the use of combined inhaled glucocorticoid and bronchodilator, formoterol, as needed in patients with worsening asthma, may reduce the risk of the exacerbation becoming severe enough for the patient to seek urgent care, Beasley noted.

Compared with the albuterol group, patients in the budesonide-formoterol or maintenance budesonide groups had a greater reduction in FENO*** from baseline (median, from 37 to 26 parts per billion [ppb] or from 38 to 25 ppb, respectively vs from 40 to 36 ppb), “which indicates that in patients with mild asthma who have not been treated previously with a glucocorticoid, airway inflammation as measured by FENO is highly responsive to inhaled glucocorticoid therapy,” said Beasley.

Patients on budesonide-formoterol also had a lower Asthma Control Questionnaire-5 score than those on albuterol alone (mean difference, -0.15, 95 percent CI, -0.24 to -0.06), which indicates less impairment with budesonide-formoterol. The budesonide maintenance group had a lower score than the budesonide-formoterol group (mean difference, 0.14, 95 percent CI, 0.05–0.23).

On the other hand, the budesonide-formoterol group had a lower mean dose of inhaled glucocorticoid than the budesonide maintenance group (107 μg vs 222 μg per day), showing that “the greater benefit was achieved despite exposure to less than half the amount of ICS preventer medication because the ICS works better when taken as needed in mild asthma,” Beasley noted.

“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,” said Beasley.

“Our trial [also] 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 …  ahead of SABA reliever therapy, … [although ICS-formoterol] is often not prescribed or taken,” Beasley said. [Global Initiative for Asthma (GINA) home page. 2018 (http://www.ginasthma.org/)]

“The findings from this study are exciting and have the potential to be a gamechanger in the way doctors treat mild asthma,” he added.

*Novel START: Novel Symbicort Turbuhaler Asthma Reliever Therapy

**SABA: Short-acting β2-agonist

***FENO: Fraction of exhaled nitric oxide