article321

Novel START

"As-needed Budesonide–Formoterol in Mild Asthma". The New England Journal of Medicine. 2019.

Clinical Question

In adults with mild asthma, is as-needed budesonide–formoterol more effective than as-needed albuterol and budesonide maintenance therapy plus as-needed albuterol in preventing asthma exacerbations?

Bottom Line

In adults with mild asthma, as-needed budesonide–formoterol reduced the rate of asthma exacerbations compared with as-needed albuterol and was superior to both as-needed albuterol and budesonide maintenance therapy plus as-needed albuterol in reducing the risk of severe exacerbations.

Major Points

This 52-week, open-label, randomized, parallel-group, controlled trial assessed the efficacy of as-needed budesonide–formoterol in mild asthma. Among patients previously taking only a short-acting β2-agonist (SABA), those using as-needed budesonide–formoterol had lower rates of asthma exacerbations than those using albuterol alone. The risk of severe exacerbation was also lower with as-needed budesonide–formoterol compared to both albuterol alone and budesonide maintenance therapy with as-needed albuterol. These results suggest that budesonide–formoterol as-needed therapy has a role in asthma management without the need for regular maintenance therapy.

Guidelines

No information provided regarding guidelines.

Design

- Multicenter, randomized, open-label, parallel-group, controlled trial
- N=668 adults with mild asthma
- Interventions:
1. Albuterol as needed (n=224)
2. Budesonide maintenance plus as-needed albuterol (n=222)
3. As-needed budesonide–formoterol (n=222)
- Duration: 52 weeks
- Primary outcome: Annualized rate of asthma exacerbations

Population

- Inclusion Criteria: Adults aged 18-75 with a doctor’s diagnosis of asthma, using only a SABA in the previous three months.
- Age: Mean 44.8 years
- Female: 66%
- Smoking history: 10.8%

Interventions

- Patients were randomly assigned to one of three groups in a 1:1:1 ratio.
- Albuterol group received 100 μg as needed for symptoms.
- Budesonide maintenance group received budesonide 200 μg inhalation twice daily plus as-needed albuterol.
- Budesonide–formoterol group received 200 μg budesonide and 6 μg formoterol as needed for symptoms.

Outcomes

- Primary Outcomes: The annualized exacerbation rate was lower in the budesonide–formoterol group compared to the albuterol group (0.195 vs. 0.400 per patient-year). There was no significant difference between the budesonide–formoterol and budesonide maintenance groups.
- Secondary Outcomes: The number of severe exacerbations was lower in the budesonide–formoterol group than in the other two groups.
- Other Observations: Budesonide maintenance treatment provided better control of asthma symptoms.
- Inhaler adherence: Overall adherence to budesonide maintenance was 56%.

Criticisms

- More frequent clinic visits than expected in routine clinical practice.
- Open-label design may introduce bias.
- Exacerbation rate was lower than anticipated, but the relative rate difference was greater than predicted.

Funding

- AstraZeneca and the Health Research Council of New Zealand.