Tailoring COPD Treatments Among Smokers, Nonsmokers

It is important that clinicians are able to stratify disease severity and exacerbation risk in treatment for patients with chronic obstructive pulmonary disease (COPD), says Klaus Rabe, MD, PhD, chest physician and professor of medicine, University of Kiel.

This transcript was lightly edited.

Transcript

How does the reduction in exacerbations with itepekimab vary among former smokers with different prior exacerbation frequencies, and what might explain these differences?

Well, itepekimab is a different story; it is not addressing IL-4 [interleukin-4] or IL-13. It is addressing IL-33. We're very much dependent on epithelial biology, this is where these alarms are coming, and the data that we have so far were quite surprising in the sense that if you look at a group of individual smokers [and] nonsmokers, the signal of exacerbation reduction was much bigger in those individuals that stopped smoking compared to current smokers. So, the overall efficacy failed its primary endpoint in that trial phase 2a, but [when] looking at the nonsmokers, 50% of that population, the effects were quite sizable.

What is also surprising, because it's a little bit against all odds of my understanding so far, is that when we looked at these nonsmokers that have a good effect on exacerbations that group and we looked at their prior history of exacerbations in it, it didn't seem to make a difference whether you had 2 or 3 or more exacerbations. The benefit of the drug was comparable. So clinically, it means that, from the data, albeit that the smokers did not respond that well, then the nonsmokers, even if they frequently exacerbate, this drug that addresses IL-33 may be a therapeutic option in the future, and that is exciting.

What are the potential implications of these findings for tailoring COPD treatment strategies in former smokers with varying exacerbation risks?

The question really of stratification of disease severity has been impairment of nonfunction at baseline, but also the risk of having exacerbation. So, it's something that that drives outcome, it drives morbidity, [and] it drives mortality. We know that. So, the prospect of having a drug available that would stimulate physicians and patients to stop smoking is one point of it. Or in more simple terms, people that have stopped smoking, you have for those individuals now an option of novel treatment on top of their regular medication. That still doesn't keep them exacerbation free, but it can afford them a further significant reduction of exacerbation.