Fernando Martinez, MD, MS, chief of the Pulmonary and Critical Care Medicine Division, Weill Cornell Medicine, New York, continues a conversation about the updates in the 2023 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (COPD).
In the second part of a conversation with Fernando Martinez, MD, MS, chief of the Pulmonary and Critical Care Medicine Division, Weill Cornell Medicine, New York Presbyterian, New York, he goes into further detail on the 2023 global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (COPD) released last year by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Martinez describes the burden of COPD mortality and the impact on the health care system, and the case for intervening in the disease at a younger age.
You noted that eosinophil counts are estimates. What other factors or considerations are you looking at when you're selecting COPD treatment for a patient?
Clearly the patient's clinical scenario is important. And so, we just talked about a person who is symptomatic, a person who has exacerbation risk, the eosinophil count obviously—those things are all medical components. But there are a series of other practical approaches. Can the patient use an inhaled device? Can they trigger a [metered dose inhaler] MDI? Do they need a soft mist inhaler? And then, what did they have access to? So, if you're in a situation where all you have access to is 2 different drugs or drug classes, then it's going to be one of those 2 or 2 different drug classes. And so, they're just a series of components that relate, that are not just the scientific principles of exacerbation reduction, symptomatic improvement, but just practical components of what the patient can or can't do, and what the patient has access to or doesn't have access to.
How does triple therapy compare to traditional inhaled corticosteroids (ICS)/ long-acting beta-agonists (LABA) therapy in COPD management?
The data are well defined, that triple [therapy] does better than dual, than ICS/LABA in most of, if not all of, the endpoints in very well done clinical trials. And so, that was why the change was made. But, you know, I think that there are still patients, particularly those where asthma is playing a bit of a role, where I still think that there is a potential role there.
Could you please discuss the burden of COPD mortality and the impact on a health care system?
COPD remains a highly morbid condition. It is estimated to become the third-leading cause of death…. So, COVID overtook COPD…. And you know, now that the pandemic is quote-unquote over—which is not the case—I think COPD globally has continued to be one of the few disorders for which there has been little plateauing and a continued gradual increase in morbidity and mortality. It remains a major burden. It's still one of the top negative impacts on the US health care system with regards to costs and a lot of those costs in the US relate to exacerbations and particularly hospitalizations for exacerbations. So, for a group like people who read The American Journal of Managed Care®, you know, they've got to manage care, and they've got to manage costs, and COPD is a driver of a lot of costs.
What evidence did the IMPACT and ETHOS trials provide regarding COPD mortality, and how do dual therapies impact COPD mortality compared with triple therapies?
IMPACT and ETHOS, those are those 2 large studies that I mentioned in a very unique COPD population who were very high-risk people, lots of exacerbations, very symptomatic. And in both studies, a significant chunk of those patients had required hospitalization. It's one of the sickest populations of COPD patients in a pharmacotherapy study. And both of those studies clearly demonstrated an all-cause mortality benefit. And what's interesting to me is—I was involved in both studies—was that even though there were 2 separate pharmaceutical companies doing the studies, with very similar inclusion criteria, the results were almost identical. The magnitude of reduction of mortality was numerically very similar. And all-cause adjudications were very similar. It's very clear that there is a mortality benefit in a defined COPD population when you were using a triple inhaled therapy.
What evidence is needed to support earlier use of triple therapies in COPD patients and how can payers support earlier utilization of triple therapies?
I think that when you're a group that manages care, and manages cost of care, I think that payers need to understand that in a well-defined population of COPD, inhaled triple therapy clearly has a beneficial effect, certainly to the patient. Because symptoms improve, exacerbation reduction improves, and so on. But the morbid conditions also improve. So, for example, in the IMPACT study, hospitalization rates decreased with triple versus the combinations. And that drives a lot of costs for managed care. I think that managed care should be very understanding of these studies that have been done, where in again, a well-defined patient population with COPD—not everybody with COPD, but a defined high-risk population of COPD—triple [therapy] should be used and should be used earlier to mitigate these bad effects to patients and to the health care system.
Are there risks to utilizing triple therapy earlier in treatment lines? If so, what are they?
You know, there are risks for utilizing triple therapy earlier—they’re more expensive. So, there’s some financial implications of doing that. And steroids themselves, long-term use of inhaled steroids, is not a totally benign therapy. Steroids are associated with pneumonia, there’s clearly a pneumonia risk, they’re associated with osteoporosis, no question about it. They may increase the risk of some atypical micro-bacterial infections, cataracts—I mean, it’s not a completely benign treatment. Which is again, why, the GOLD strategy has increasingly become much more personalized therapy with this quadrant system.
And then there was a large emphasis on being able to personalize treatment. And I think that triple therapy fits within that personalization. It’s clear that it’s beneficial for a group of patients—not all patients. In fact, probably a minority of patients. And I think that the groups that manage access, the payers, need to understand that that potential modest amount of upfront cost, clearly has benefits to the patients and will have benefits to the health care system in general, because of the decreasing morbidity.
How has the 2023 GOLD report addressed unmet needs in the management of COPD?
There are a lot of unmet needs in COPD, unfortunately. And I think that every one of our chapters now has some descriptions regarding what some of those unmet needs are. We don't have any treatments that are known to cure the disorder. We have very little data with regards to earlier institution of therapies, earlier being in younger individuals, and whether providing therapy at a younger age is more likely to either decrease the risk of developing COPD or decrease the risk of COPD progression in those individuals.
And those areas right now are two of the hottest areas in our field, which is earlier diagnosis and early institution of therapy. One of the early diagnostic process [is in] a paper that we [some of us on the GOLD science committee] published in JAMA. It's called CAPTURE. That is a COPD case-finding approach. There’s actually a new section in GOLD, reviewing all of the COPD case-finding approaches, which is a way of trying to diagnose COPD earlier. And to be able to identify people who are undiagnosed with COPD, so that one can institute earlier therapy.
And so, this whole idea of early identification, identifying risk factors for disease, and disease progression earlier in life, potentially instituting therapies earlier—all this “early” is chronologically earlier—I think that that's a really, really hot area right now.
How will the 2023 GOLD report impact COPD management?
Will it impact COPD management? I certainly hope so, we spend a lot of time making these changes, so it will be a waste of our hours if it doesn’t get incorporated. We’re doing so many things in COPD right now. COPD is really an exciting area, there’s been a lot of movement.
This whole thing with early diagnosis in CAPTURE is really exciting. There are a whole bunch of studies that are ongoing, trying to better characterize patients, being able to identify at-risk groups early, to be able to look at new therapeutics. There have been a couple of studies recently conducted that suggests that there are some new therapies that are very new. We haven't had a new class of drugs in COPD in more than a decade. And there are probably two that will be coming shortly. And then there are a whole bunch of biologic studies, you know, a lot of these asthma therapies, targeting [interleukin] IL-5, IL-33, [thymic stromal lymphopoietin] TSLP. There are, I think there are 7 or 8 ongoing studies of biologics. And that's revolutionized asthma.