As-needed budesonide-formoterol in mild asthma reduces severe exacerbation risk

By Bianca Nogrady
Treating mild asthma with a combination of budesonide and formoterol (eformoterol) taken as needed when patients have symptoms could result in significantly fewer severe exacerbations, according to a study published in The New England Journal of Medicine.

The one-year open-label, parallel-group Novel START study randomised 668 people with mild asthma to inhaled salbutamol (albuterol as-needed, twice-daily budesonide with as-needed salbutamol (budesonide maintenance group), or a combination of inhaled budesonide and formoterol (eformoterol) as needed. All patients had only used short-acting beta-agonist therapy in the previous three months.

The number of severe exacerbations in the budesonide-formoterol (eformoterol) as-needed group was 60% lower compared with the salbutamol as-needed group, and 56% lower than seen in the budesonide maintenance group.

The study also showed a significant 51% lower annualised overall exacerbation rate in the budesonide-formoterol (eformoterol) group compared with the salbutamol as-needed group, although this rate was similar to that seen in the budesonide maintenance group. Participants taking the budesonide-formoterol (eformoterol) combination as-needed had about half the mean dose of inhaled corticosteroid compared with those in the budesonide maintenance group.

Commenting on the outcomes, study coauthor Professor Helen Reddel, from the Woolcock Institute of Medical Research, Sydney, said the study was a ‘real-world’ follow on from the previous SYGMA (Symbicort Given as Needed in Mild Asthma) studies published last year.

‘The SYGMA studies were double-blind, with patients in all three randomisation groups required to take a twice-daily inhaler, so we also needed evidence for the way in which this treatment would be used in real life,’ she told Medicine Today.

‘The Novel START study confirmed that the as-needed regimen was as good as the regular treatment for the primary outcome.’

Professor Reddel said the study highlighted the risks of treating asthma with a reliever inhaler alone, and showed that the combination as-needed approach delivered twice the benefit with half the corticosteroid dose compared with maintenance budesonide.

Meanwhile, a placebo-controlled crossover study in the same issue of The New England Journal of Medicine looked at the outcomes of 12 weeks’ treatment with tiotropium, mometasone or placebo in patients with mild asthma, based on baseline sputum eosinophil levels.

This found that many patients with two low sputum eosinophil levels (less than 2%) – who by design represented almost three-quarters of patients in the study – responded similarly to either tiotropium or mometasone. However, Professor Reddel noted that longer-term studies were needed to evaluate the safety of asthma treatments, with regard to risk of serious exacerbations, and stressed that this was a proof-of-concept study that did not have direct relevance for clinical practice.
N Engl J Med 2019; 380: 2020-2030.
N Engl J Med 2019; 380: 2009-2019.