In a talk during a breakfast session at the TSANZSRS conference last week GOLD committee member Professor Alvar Agusti from Barcelona gave delegates his thoughts on why the debate around the use of inhaled corticosteroids in COPD continues despite clear guidelines.

 Why the debate?

There is a lot of debate about the position of inhaled corticosteroids (ICS) in the treatment of COPD, with many scientific conferences dedicating sessions to the topic, Agusti told delegates attending the A. Menarini breakfast session Beyond COPD phenotypes – what is next.

But if you look at the GOLD document there should not be a debate, he said.

“It is very clear… the guidelines say long-term treatment with ICS is recommended in patients with FEV1 lower than 50 and/or frequent exacerbations not able to be controlled by long-acting bronchodilators – evidence A,” he told the audience.

And long-term monotherapy with ICS is not recommended in COPD because it is less effective than the combination of ICS with a LABA – also evidence A.

“It’s pretty clear so why the debate?” he asked the audience.

Alternatives and overuse

According to Agusti one of the major driving forces behind the debate is that we now have alternatives.

To some extent COPD inherited drugs developed for asthma but over the past five to ten years this has changed and we now have drugs specifically for COPD like long-acting bronchodilators.

“Now we can treat with a LABA or LAMA alone or combined and this repositions everything including inhaled steroids,” Agusti said.

Also now that we actually have alternatives we probably realise that we have been overprescribing ICS in COPD.

Real-world data indicates that a large number of low-risk patients are being prescribed ICS despite guidelines stating they should not receive them, Agusti told delegates.

“I think that the availability of novel bronchodilators alone or in combination will force all of us to reposition and reduce this over prescribing,” he said.

Pneumonia

Another reason behind the ongoing debate on whether ICS should be used in COPD is that many papers have linked their use to an increased risk of pneumonia.

However, most studies found either no difference or a reduction in pulmonary and overall mortality with their use.

“So it seems there is a dual effect, yes ICS in COPD is linked to what we think is pneumonia but certainly they [ICS] did not increase the risk of mortality and sometimes reduced it,” he said.

Withdrawing ICS in COPD patients

A concern around what happens if you withdraw inhaled steroids in patients with COPD is also most likely fuelling the debate, Agusti said.

The WISDOM study published late last year in the NEJM found there was no increased risk of exacerbations if you withdraw ICS from patients.

However, according to Agusti the study had several important limitations, such as studying the wrong patient population.

In his view the authors included patients who were less likely to respond to ICS and excluded those most likely to respond.

The outcome that nothing happened was hardly surprising, he said.

Another element often forgotten in the debate is the dose of ICS in COPD, with studies showing different doses produce the same improvements in lung function.

“In other words it is possible that we are using too high doses of steroids in COPD and maybe a reduced dose can provide some benefits and reduce some risks – this has to be shown of course,“ he told the audience.

A summary of Agusti’s view of ICS in COPD

• There is ICS overuse in COPD
• Never use them alone in COPD
• New dual bronchodilator combination will likely reposition ICS use in COPD
• Some groups of patients with COPD might benefit from ICS for instance those with exacerbations despite optimum bronchodilator therapy
•  There are data confirming that some biomarkers, for example eosinophils in blood, may identify a group of patients with COPD who are particularly responsive to ICS
•  It is possible to reduce the dose of ICS and maybe have a positive effect on the efficacy / safety ratio

The debate could be laid to rest

The results of studies on the horizon could finally put the debate to rest, said Agusti.

For instance, there is emerging data that ICS might reduce the risk of lung cancer.

At the same time the ongoing SUMMIT study of more than 16,000 patients with moderate COPD is looking at whether ICS can reduce mortality and cardiovascular disease.

Its results will be published at the end of the year and if they are positive the debate is over, said Agusti.

“We will see,” he concluded.