The suitability of bronchial thermoplasty (BT) as a treatment option for severe asthma remains up in the air because of a glaring absence of placebo controlled trials, an expert panel has concluded.
In a pro and con debate that weighed more heavily on the ‘cons’, TSANZSRS17 delegates were left wondering if the controversial procedure really is the ‘new frontier’ in severe asthma that several camps claim it is.
Associate Professor David Feller-Kopman from the John Hopkins Hospital in the US was tasked with presenting the ‘pros’ side of the debate. However, taking the packed auditorium through the published trials, he struggled to find many positives.
He said that while the AIR2 trial had a sham procedure arm it had a number of short falls. For example, patients in the trial did not have severe asthma (mean FEV1 78%).
“The study excluded patients who had severe disease. These are the very patients that are referred to me now and we don’t have the data to suggest that it’s safe to do the procedure,” he told delegates.
He added that it was also debatable whether FEV1 was the most relevant outcome measure – both for thermoplasty and lung volume reduction studies.
“FEV1 is an interesting physiological measure but patients don’t necessarily care about their FEV1. What they care about is exacerbations and symptoms… defining patient related endpoints in future trials are perhaps the more important variables to be measuring,” he said.
According to Professor Feller-Kopman another issue with AIR2 trial was that the statistically significant improvement seen in the Asthma Quality of Life Questionaire (AQLQ) score in the intervention group was less than the predefined clinically meaningful change.
However, by far the biggest criticism of the study was that the sham group also had significant improvements in AQLQ. “The placebo effect is strong,” he said.
Taking up the ‘con’ side of the debate Professor Sally Wenzel from the University of Pittsburgh did not hold back, revealing that putting together a top 10 list of reasons NOT to do BT was “a pretty easy job”.
Sally Wenzel’s 10 reasons to not do BT in severe asthma
- Severe asthma consists of many different phenotypes and there is no guidance on which patients may respond best to the procedure.
- Rationale for improving severe asthma by reducing smooth muscle mass is modest
- Small airways disease extends well beyond reach of probe
- Objective placebo controlled data on BT is available on only 200+ patients, without sinusitis and with relatively preserved FEV1
- BT is expensive and potentially dangerous in the short term
- Some pulmonologists/respirologists do not know the difference between difficult asthma, vocal cord dysfunction and severe asthma
- Compared to newer biologics, effects on exacerbations, FEV1 and symptoms are small
- Long term efficacy and safety unknown
- Actual mechanism for any “efficacy” unknown
- ERS-ATS guidelines suggest only doing as part of a clinical trial/registry
She said the bottom line was that we really need more evidence for the procedure.
“Without placebo controlled trials we have to maintain a scepticism,” she said.
“For the vast majority of asthmatic patients better options probably do exist,” she told delegates, conceding that there may be some patients who would benefit from the procedure.
“My overall suggestion is to make BT the option of last resort,” she concluded.
Speaking during the question time following the debate leading asthma expert Professor Helen Reddel from the Woolcock Institute said that the “magic” that had appeared in earlier trials had to some extent “coloured the way we have proceeded.”
“If you think about this in terms of medication, bronchial thermoplasty wouldn’t be registered at the moment because we only have one placebo controlled study” she told delegates.
“The population with severe asthma is an extremely stressful population – for all of us.
For the patients there is immense emotional and physical stress and for clinicians there is stress in dealing with ongoing symptoms and exacerbations.”
“I don’t think we should underestimate that effect in terms of the placebo effect,” she added.