Exploring the Differential Effectiveness of ICS by Smoking Status in COPD

Our findings explores the emerging evidence that inhaled corticosteroids (ICS) may be less effective in current smokers compared with nonsmokers with chronic obstructive pulmonary disorder (COPD), says Alexander Mathioudakis, MD, PhD, clinical lecturer in respiratory medicine at The University of Manchester.

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

Transcript

What specific advantages does long-acting β-agonist plus long-acting muscarinic agonist (LABA+LAMA) therapy offer over LABA plus ICS in managing COPD symptoms in current smokers?

There have been studies suggesting that the inhaled corticosteroids are not as effective in current smokers compared to ex-smokers. In our analysis of the FLAME trial, we tried to see whether that's true, and our study seems to support this opinion. So, among ex-smokers, we found the anticipated association between eosinophils and treatment response. In people with low blood eosinophils, we found out that a combination of a long-acting β-agonist with a long-acting muscarinic [agonist] was superior to LABA+ICS. And then in higher blood eosinophils, we found a trend over better response to LABA+ICS compared to LABA+LAMA.

Then when we looked at groups of patients that we know from our analysis are respondents—people who have a significant suppression of their blood eosinophils on inhaled steroids—in this group of patients, in ex-smokers, LABA+ICS was superior to LABA+LAMA; that's as we would have expected. Now, when we looked at the subgroup of current smokers, LABA+LAMA was consistently superior to LABA+ICS, and that tell us that probably current smokers don't get the same benefit from inhaled corticosteroids.

How might the findings from the FLAME trial post hoc analysis influence treatment guidelines for patients with COPD who are current smokers, particularly those with varying eosinophil counts?

Our post hoc analysis of the FLAME trial is an exploratory study, so we still need to validate our findings. We have a good message, but we need to further validate the results before having strong enough evidence to inform guidelines. So, what we have been doing is that we have started an individual participant data meta-analysis called the ICS-RECODE study, and we have applied and gained access to data from 20 mega trials looking at the effectiveness of inhaled corticosteroids for COPD. And we are reanalyzing these trials and trying to look at predictors of treatment response. One of the predictors that we are looking at is the smoking state, to show if this meta-analysis confirms the findings that smokers appear resistant to inhaled corticosteroids, then I believe, that will be the time to inform the guidelines.