In patients with mild asthma, even a single day of repeated use of as-needed ICS–formoterol can protect against short term risk of a severe exacerbation as effectively as regular maintenance ICS, new research shows.
While studies such as the 2018 SYGMA trials have already shown as-needed low-dose budesonide–formoterol reduces the long-term risk of severe exacerbations compared with as-needed SABA, a post-hoc analysis from SYGMA 1 published in The Lancet Respiratory Medicine has now extended those findings.
SYGMA 1 comprised almost 4,000 patients randomised to one of three regimens – either twice-daily placebo plus budesonide–formoterol as-needed, twice-daily placebo plus terbutaline as-needed, or twice-daily budesonide (200 μg) plus terbutaline as needed.
Amongst its outcomes, it found budesonide–formoterol used as-needed for relief of symptoms resulted in a 64% lower rate of severe exacerbations than as-needed terbutaline.
The current post-hoc analysis showed that even a single day of repeated use of as-needed low-dose ICS–formoterol can reduce the risk of a severe exacerbation developing in the following 21 days compared to SABA alone.
“After the first day with more than two as-needed inhalations, the adjusted hazard ratio (HR) for a severe exacerbation in the subsequent 21 days was 0·27 (95% CI 0·12–0·58; p=0·0008) and after the first day with more than four as-needed inhalations the HR was 0·24 (0·10–0·62; p=0·0030) with as-needed budesonide–formoterol compared with as-needed terbutaline,” the study said.
“Similarly, the HR for a severe exacerbation with budesonide maintenance compared with as-needed terbutaline was 0·39 (0·19–0·79; p=0·0091) after the first day of more than two as-needed inhalations and 0·30 (0·13–0·72; p=0·0065) after the first day of more than four as-needed inhalations the odds of having a week with well-controlled asthma during the 52-week trial period were 14% higher in the budesonide–formoterol group than in the terbutaline group.”
The investigators said their findings suggest that in adults and adolescents with mild asthma repeated use of as-needed low-dose ICS–formoterol as soon as symptoms start to worsen can protect against exacerbations as effectively as regular maintenance ICS.
And it appeared that the greater the severe exacerbation risk – as seen with higher reliever use – the greater the benefit of as-needed budesonide–formoterol.
“These findings support the use of an anti-inflammatory reliever to reduce the risk of severe exacerbations in asthma and to exploit the natural relief-seeking behaviour of patients in such contexts via the rapid provision, when needed, of increased doses of both ICS and formoterol,” the study authors concluded.
Pushback on puffer choice
Senior investigator Professor Helen Reddel, from the Woolcock Institute of Medical Research, told the limbic she did not want people to interpret the findings as reflecting a ‘laissez-faire’ approach to asthma management. .
“My fear is it is being interpreted as such and we have been really careful to emphasise in everything we have said that if you have been prescribed regular treatment you do absolutely need to take it regularly.”
“Because if someone is poorly adherent, that is different from what is done with this as-needed strategy.”
She said surveys, questionnaires, qualitative interviews & electronic monitoring had shown that patients with sub-optimal adherence take their preventer for a few days or weeks and then none at all for blocks of time.
“And that means that during those periods of time, they are just taking their SABA alone. And we know that when asthma starts to worsen in someone who is not adherent they increase their SABA and then quite late in the piece they remember that they are meant to be taking a preventer.”
“And those patterns are completely different from this strategy – that whenever you take your reliever inhaler, you get some inhaled corticosteroid as well as an effective bronchodilator.”
Professor Reddel said a variety of large studies had now shown that the worst option in people with mild asthma is taking SABA only.
Yet there was some strong push back by some people, including in Australia.
“Some clinicians feel quite apprehensive about this – that it will be seen as encouraging poor adherence.”
“I think it’s also a fundamental change to move away from starting asthma treatment with SABA alone, and my view is it will take many years for this to work through the system especially in Australia where SABA is available over-the-counter.”
“On multiple occasions over the last 20 years, asthma organisations and clinicians have discussed the possibility of making the SABAs prescription only and each time we have concluded that it is not feasible. Patients have an expectation that this is their right,” she said.
“It’s complicated and challenging and I think it will take quite a long time to gain acceptance but there is increasing evidence about the risk of just SABA only treatment.”
Professor Reddel said the concept of a population level risk reduction strategy was not yet widely accepted for asthma.
“If you think about antihypertensives or even vaccines, we make population level recommendations to reduce risk but the individual person with high blood pressure or high cholesterol or who gets a vaccine, they never know if they have been one who has benefited from it.”
“I regard this as something that should be thought of at a population level rather than trying to decide in an individual patient whether you should have SABA alone or this strategy of as-needed, low dose budesonide-formoterol.”
She added that phenotyping was not required for this strategy.
“In patients with moderate or severe asthma, there is increasing evidence about the benefit of phenotyping patients but the Novel-START and PRACTICAL studies showed that this didn’t apply in mild asthma – that patients who didn’t have high FENO and didn’t have high eosinophils at baseline, still did just as well with as-needed budesonide-formoterol. They did better than with SABA alone and better than with regular ICS.”