In the era of biologics, too many patients with asthma are being unnecessarily exposed to systemic steroids, a respiratory physician says.
Speaking at the British Thoracic Society (BTS) Summer Meeting 2022, Dr David Jackson, a consultant in severe asthma and eosinophilic lung diseases and the Clinical Lead for Guy’s Severe Asthma Centre, London, said he believes that, to date, many asthma patients may have died not from asthma itself but from complications related to the systemic steroids they were exposed to.
For many years, steroids were the only realistic option for patients with severe asthma and “this has led to an enormous amount of irreversible steroid-related morbidity”, he said.
Now, with the introduction of targeted biologic therapies, which “have totally transformed” the lives of patients with severe asthma, “only a very small proportion still require daily oral steroids once they are initiated on biologics”.
In fact, no patient with asthma should be taking daily prednisolone in the absence of a targeted biologic, Dr Jackson told delegates.
“Either they genuinely need that prednisolone, in which case they should be on a biologic, or they don’t need that prednisolone at all.”
Unfortunately, many patients are still being unnecessarily exposed to the harmful effects of systemic steroids, which is largely down to two major problems: delays in getting referred to see a specialist, and a failure to use biomarkers of inflammation to guide steroid use, he said.
In order to attain the best treatment outcomes, it is essential that respiratory physicians “trust biomarkers”, such as FeNO and blood eosinophil levels, to guide treatment regimens, as steroids only really work if there is type 2 inflammation, Dr Jackson reminded delegates.
But swathes of patients are still being treated with steroids even though their symptoms are not from type 2 inflammation, despite the tools being readily available to identify those for whom such treatment would be appropriate.
Data from Guy’s Hospital’s Severe Asthma Centre showed that of 24 patients referred from other hospitals with completely normal T2 biomarkers and maintenance prednisolone therapy at an average dose of 15 mg/day, around 70% could be weaned off their steroid treatment after just 8 weeks with no significant impact on symptom scores or rise in T2 biomarkers.
“A large number had been taking daily prednisone for over a decade when they were referred, and appear to have been left on maintenance prednisone completely inappropriately,” he said.
In the majority of cases it was clear that a co-morbidity driving respiratory symptoms such as severe obesity, GORD, breathing pattern disorders, laryngeal dysfunction and/or psychological conditions had not been accurately identified by the treating physician as the main driver for the patients’ symptoms. As a result, steroid treatment was continuously escalated with the assumption that steroid resistance rather than an incorrect diagnosis was the underlying problem.
Studies involving biologics in part highlight the same issue — in the Phase III VENTURE trial of dupilumab, placebo alone allowed an approximate 50% reduction in maintenance prednisolone, while just under 30% of patients were able to stop prednisolone altogether.
Similarly, in the SOURCE study with tezepelumab, 46% of patients were able to completely stop prednisolone treatment “just with placebo and not with a very expensive biologic”, he said.
This, he said, was the consequence of two different problems: either the prednisone was prescribed despite well-controlled airways inflammation and was therefore unnecessary, or the improvement in treatment adherence to ICS in trial participants with T2 inflammation was sufficient to control the inflammation and the prednisolone was not required either. This fundamentally highlights the importance of optimising background care, he noted.
Huge gains in treatment outcomes can be achieved by improving ICS adherence and inhaler technique.
“In reality, as seen in the placebo arms of clinical trials of biologics, the magnitude of these gains usually exceeds the added benefit of biologics,” Dr Jackson stressed.
At a population level, focusing attention on improving these factors will continue to have the biggest impact on reducing steroid-related morbidity.
Dr Jackson has undertaken consultancy work for several biologics manufacturers.