Study of the differential effectiveness of ICS depending on smoking status in COPD

Our findings explore new evidence that inhaled corticosteroids (ICS) may be less effective in current smokers compared to non-smokers with chronic obstructive pulmonary disease (COPD), says Alexander Mathioudakis, MD, clinical lecturer in respiratory medicine at the University of Manchester.

The results were presented at International Congress of the European Respiratory Society 2024.

Transcript

What specific benefits does a long-acting β-agonist plus a long-acting muscarinic agonist have? Proposed therapy (LABA+DAMA) versus LABA plus ICS in the treatment of COPD symptoms in current smokers?

There have been studies showing that inhaled corticosteroids are not as effective in current smokers compared to former smokers. In our analysis FLAME trial we tried to find out if this is true, and our study seems to confirm this opinion. In summary, among former smokers we found the expected association between eosinophils and treatment response. In people with low blood eosinophil levels, we found that the combination of a long-acting β-agonist with a long-acting muscarinic (agonist) was superior to LABA+ICS. And then in higher eosinophils in the blood, we found a trend towards a better response to LABA+ICS compared to LABA+LAMA.

Then, when we looked at the groups of patients that we know from our analysis are responders—people who have significant suppression of blood eosinophils on inhaled steroids—in this group of patients, in former smokers, LABA+ICS was superior to LABA+ . LAMA; this is what we expected. Now when we looked at the subgroup of current smokers, LABA+LAMA was consistently superior to LABA+ICS, which tells us that current smokers are likely not getting the same benefit from inhaled corticosteroids.

How might the results of a post hoc analysis of the FLAME study influence treatment recommendations for patients with COPD who are smokers, especially those with different eosinophil counts?

Our post hoc analysis of the FLAME study is an exploratory study, so we still need to confirm our findings. We have a good idea, but we need to test the results further before we have strong enough evidence to base a recommendation. So we started a meta-analysis of individual participant data called ICS-RECODE study, and we applied and accessed data from 20 mega-studies examining the effectiveness of inhaled corticosteroids in COPD. And we’re reanalyzing these studies and trying to look at predictors of treatment response. One of the predictors we look at is smoking. To show that if this meta-analysis confirms the findings that smokers appear to be resistant to inhaled corticosteroids, then I believe it is time to report this in guidelines.