Too early to use thermoplasty before biologics in severe asthma: expert


By Mardi Chapman

15 Jun 2020

It would be premature to offer bronchial thermoplasty before mepolizumab in severe asthma despite a study showing unique benefits of the procedure, a respiratory physician says.

Professor Peter Wark from the Centre of Excellence in Severe Asthma in Newcastle says a new Victorian study provides interesting new information on thermoplasty but a randomised controlled trial is needed before changing practice.

A comparison of the two treatments in an observational study at a severe asthma clinic in a Victorian hospital found that they were equally effective in reducing symptoms, exacerbations and oral steroid use over one year follow up. And unusually, thermoplasty was effective regardless of eosinophilic phenotype.

The study led by Associate Professor David Langton of the Department of Thoracic Medicine, Frankston Hospital, Melbourne, followed up 91 patients with severe asthma, of whom 47 patients were treated with mepolizumab and 44 received bronchial thermoplasty.

Except for significantly higher blood eosinophil count in the mepolizumab group, at baseline the patients had similar characteristics (mean Asthma Control Questionnaire [ACQ]  score 3.5, FEV1 51.4%, 48% on maintenance oral steroids 48.3% and taking a mean of 11.5 inhalations/day of reliever therapy.

During 12 months of follow up there were no differences between treatment groups in outcomes for ACQ (1.9 ±1.3 mepolizumab vs 1.7 ±1.3 BT), exacerbation rate (0.9 ±1.1 vs 0.9 ±1.5), reduction in reliever use (−6.3  ±10.5 vs −5.0  ± 8.8 puffs/day) or reduction in oral corticosteroids (−3.3 ±7.5 vs − 5.8 ± 6.7 mg/day).

The FEV1 improved equally (160 ±290 vs 150 ± 460 mL).

Subgroups analysis also found that the presence or absence of eosinophilic inflammation had no bearing on the ACQ outcome, with comparable results sustained over 12 months.

In terms of adverse events, the frequency of a bronchial thermoplasty patient experiencing either a readmission, or a prolonged admission, was 18.2% over the whole treatment period. For mepolizumab, five patients (10.6%) withdrew due to a treatment-related adverse event. A further five patients withdrew from treatment (10.6%) when there was no evidence of clinical improvement, and two patients chose not to continue with their injections, finding them a nuisance. By the 12-month assessment, 12 patients (25.5%) had discontinued mepolizumab treatment.

The study investigators said the finding of comparable outcomes for the two treatments was striking, particularly as the results for thermoplasty were seen regardless of eosinophilic profile.

“This is an important observation for clinicians with significant implications for their patients,” they wrote in Respirology

Given the high cost of biologics and the inconvenience and poor adherence of regular injections, it may be worth considering bronchial thermoplasty prior to starting drug treatment, they suggested.

The findings are also good news for patients with a low blood eosinophil phenotype, they said, because treatment options are limited to macrolide antibiotics that have only modest efficacy.

“In comparison with macrolide therapy, the safety of bronchial thermoplasty beyond 12 months has a strong evidence base, and bronchial thermoplasty does avoid the potentially significant issue of long-term antibiotic resistance,” they wrote.

Bronchial thermoplasty still finding its place

However Professor Wark said that while the study had shown bronchial thermoplasty can be done safely and there seemed to be a treatment response, it was small, not randomised and there was clearly a selection bias partly related to availability of the intervention.

“It’s certainly suggestive that there is a treatment response in people with severe asthma. There seems to be no doubt about that. Both interventions looked like they improved symptoms and improved reliever use.”

“The problem remains that there still hasn’t been a prospective RCT of thermoplasty versus no thermoplasty in severe asthma.”

Professor Wark said an early trial in the field was conducted largely in milder disease.

“It met some of its outcomes but had a high placebo response as well so it got a lot of criticism over that. That didn’t stop it being utilised in the US particularly and around the world but there is still doubt as to where it sits, who should have it and who shouldn’t have it.”

He added that the lead investigator on the Victorian study had been a proponent of bronchial thermoplasty for some time and done some interesting work looking at the lung function changes and some of the clinical effects in this patient group.

“And he certainly has demonstrated a biologically plausible mechanism whereby bronchial thermoplasty could be efficacious in the setting of severe asthma.”

“Most people don’t think that it’s quite enough. There certainly hasn’t been a head-to-head comparison with monoclonal antibodies and there probably never will be.”

He said bronchial thermoplasty could be utilised not as an alternative to monoclonal antibodies but as sequential treatment.

“It’s probably targeting aspects of their disease which monoclonal antibodies aren’t targeting.”

“As a treatment for severe asthma it’s more than a fringe treatment. There is some biological plausibility; it’s just hard to know the way forward.”

“There are too many side effects and concerns about it to be broadly used in everybody with asthma. That seems inappropriate.”

“But this group with a high burden of illness – a lot of symptoms and still having exacerbations – they are an attractive group to target with a therapy like this.”

“It’s still finding its place. There does need to be more evidence and some form of randomisation to current treatments is probably what needed to bring it into the mainstream.”

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