In adults with mild to moderate asthma, budesonide-formoterol used as needed for symptom relief was more effective at preventing severe exacerbations than maintenance low-dose budesonide plus as-needed terbutaline. In this trial involving 885 adults, those using the combination inhaler as required had fewer severe asthma attacks, with similar levels of general symptom control, and overall used a lower dose of corticosteroid.
The results of this trial suggest that for people with mild asthma, exacerbations can be reduced without traditional daily maintenance therapy with a corticosteroid inhaler.
This finding supports the use of a corticosteroid-LABA combination inhaler as reliever therapy in the treatment pathway.
Why was this study needed?
Around 4.3 million adults in the UK are currently treated for asthma, costing the NHS around £1 billion each year. Most sufferers have mild or moderate disease, experiencing few symptoms, with occasional exacerbations. They may be prescribed as-needed short-acting beta-agonists (SABAs) with or without maintenance inhaled corticosteroid to help prevent exacerbations, but patients may not stick to a maintenance treatment plan.
An alternative is to use a combination of an inhaled corticosteroid with a fast-onset, long-acting beta-agonist (LABA) to provide relief when needed, alongside the anti-inflammatory effect from the steroid.
However, we don’t know enough about the safety and effectiveness of this regime, compared with maintenance inhaled corticosteroid plus as-needed SABA.
This is the first independently-funded study comparing inhaled combination corticosteroid LABA as sole reliever therapy with maintenance inhaled corticosteroid plus SABA reliever therapy in patients with mild to moderate asthma.
What did this study do?
PRACTICAL was a 52-week multi-centre randomised controlled trial. It was conducted in New Zealand during 2016/17. It involved 885 adults with mild or moderate asthma symptoms, who were using short-acting beta-agonist inhalers at enrolment with or without low to moderate doses of inhaled corticosteroids for three months.
They were randomised into two groups. The first group of 437 received combined budesonide (200 micrograms) and formoterol (6 micrograms) - one inhalation for relief of symptoms as required. The second group of 448 received budesonide (200 micrograms) - one inhalation twice daily, plus terbutaline (250 micrograms) - two inhalations as required. Participants were assessed at weeks 0, 4, 16, 28, 40 and 52. The primary outcome was asthma exacerbations, at least severe enough to need oral steroids. The Asthma Control Questionnaire (ACQ-5) was also used.
Limitations included the open-label design, though this pragmatic design means that real-life compliance was accounted for in the evaluation. This trial was well conducted, but the lower than expected rate of exacerbations meant that the confidence interval was wider than ideal.
What did it find?
- The rate of severe asthma exacerbations was low in both groups but lower with combination than maintenance steroid plus as-needed reliever therapy (absolute rate per patient per year 0.119 versus 0.172; relative rate 0.69; 95% confidence interval [CI] 0.48 to 1.00).
- When milder exacerbations needing a visit to the clinic were added, the combination inhaler remained superior (absolute rate per patient per year: 0.165 versus 0.237; relative rate 0.70; 95% CI 0.51 to 0.95).
- The ACQ-5 score for asthma symptoms did not differ between groups.
- The number of patients withdrawn because of treatment failure did not differ between the two groups (nine in the combination group and 11 in the maintenance-plus short-acting reliever group).
What does current guidance say on this issue?
In its guideline published in November 2017, NICE states that adults whose asthma is not controlled with a SABA alone, and whose symptoms clearly indicate the need for maintenance therapy (for example, symptoms are present three times a week or more), should be offered regular low-dose inhaled corticosteroid maintenance treatment.
NICE suggests that where inhaled corticosteroid maintenance therapy is needed, patients should be prescribed a regular, daily dose rather than ‘when required’ steroid therapy.
The dose should be adjusted over time, with the aim that the patient has the lowest dose required for effective asthma control. Combination inhalers are to be used when regular maintenance therapy with two other agents is not sufficient and in addition to regular maintenance inhaled steroid.
What are the implications?
This study provides additional evidence to support prescribing a combination inhaler for symptom relief for adults with mild to moderate asthma, earlier in the stepped care pathway and possibly in place of regular maintenance inhaled steroid.
It is not clear if the as-needed use of combination inhalers will come at a higher or lower cost overall than maintenance steroids plus SABA inhalers separately, but, based on this trial, better symptom control does seem possible.
Citation and Funding
Hardy J, Baggott C, Fingleton J et al. Budesonide-formoterol reliever therapy versus maintenance budesonide plus terbutaline reliever therapy in adults with mild to moderate asthma (PRACTICAL): a 52-week, open-label, multicentre, superiority, randomised controlled trial. Lancet. 2019;394:919-28.
This study was funded by the Health Research Council of New Zealand.
Asthma UK. The reality of asthma care in the UK, Annual Asthma Survey, 2018 report. London: Asthma UK; 2019.
NICE. Asthma: diagnosis, monitoring and chronic asthma management. NG80. National Institute of Health and Care Excellence. London, 2017.
Produced by the University of Southampton and Bazian on behalf of NIHR through the NIHR Dissemination Centre