Improving Primary Care for Chronic Health Conditions; New Target for Asthma and COPD

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of Texas Tech Health El Paso, look at the top medical stories of the week.

This week’s topics include a treatment for advanced breast cancer, a new target for asthma and chronic obstructive pulmonary disease (COPD), statins for older people, and improving primary care for those with chronic health conditions.

Program notes:

0:33 Statins for older people without cardiovascular disease

1:34 Followed for 6 years

2:34 70 years of age without cardiovascular disease

3:00 Improving primary care for folks with chronic conditions

4:00 70,000 respondents

5:00 Long-term relationship with a primary care provider

6:00 Continuity and coordination can be delivered at scale

7:09 Treating advanced breast cancer

8:10 Mutation in estrogen receptor

9:12 Targeting specific mutations

10:00 A new target for managing asthma and COPD

11:00 Healthy volunteers and patients with asthma

12:00 Typically treated with immunosuppression

13:05 End

Transcript:

Elizabeth: Is there a way to improve primary care for people with chronic health conditions?

Rick: Do older adults benefit from taking statins?

Elizabeth: A new pathway for managing COPD and asthma.

Rick: And improving treatment of advanced breast cancer.

Elizabeth: That’s what we’re talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: And I’m Rick Lange, president of Texas Tech Health El Paso.

Elizabeth: OK. Rick, statins, we’ve quit before. Are we going to put them in the water? What about in the New England Journal of Medicine, their purported benefits, or not, of statins in older people?

Rick: We know that statins have a lot of benefits overall and in high-risk individuals. Well, one of the high-risk features is if you’re older. So let’s take a group of individuals who are 70 years old that have never had cardiovascular disease, diabetes, they’ve never had dementia. Do those individuals, just because they’re older, benefit from taking a statin?

They had almost 10,000 participants and they randomized them to receive either atorvastatin (Lipitor) at 40 mg once daily or placebo. And they looked at two different endpoints. One is the composite death from cardiovascular disease. Do they have a heart attack or stroke, or do they need to have coronary revascularization? They also assessed what’s called disability-free survival. Was the person alive or not? Did they develop dementia or was there some persistent physical disability?

When they followed these individuals for approximately 6 years, there was, in fact, improvement with regard to cardiovascular disease. They had less cardiovascular death, less stroke, and they had less heart attacks, 20% to 30%. But overall, these individuals did not have any benefit with regard to disability-free survival. They just didn’t live any longer. They just didn’t live any better.

Elizabeth: Talk to me about how you’re going to integrate this into your practice.

Rick: What happens is, Elizabeth, even though you’re over the age of 70, and you have an increased risk of cardiovascular disease, these individuals died of other things. I think you have to look the person in the eye and say, “Hey, this will improve your cardiovascular outcomes, but it doesn’t improve your overall outcomes.” And I think most of us would say, you know what, I’m really not sure there’s much of a benefit. So that’s the way I approach it, but I think it’s a shared decision. But we’ve never done a randomized trial in this particular patient group. Again, it’s a very good trial.

Elizabeth: I’m going to look at it from maybe a slightly more positive aspect, which is this conclusion that if you’ve aged to 70 and you haven’t manifested cardiovascular disease in any way, that, oops, guess what, you probably don’t need a statin at this point.

Rick: And by the way, I think that’s a fair way to analyze it. Did the statin lower cholesterol levels in these individuals? Absolutely, about 35%. And the statin didn’t do anything to decrease their overall risk of death.

Elizabeth: OK. Let’s turn to The Lancet. Another really big study. Is there a way that we can improve primary care for folks with chronic conditions? What they’re doing here is trying to examine factors that are related to high-quality primary care and employing the patient’s perspective in this whole thing, which clearly is something I’m very passionate about.

So they did a secondary analysis of cross-sectional Organisation for Economic Co-operation and Development Patient-Reported Indicator Surveys. This included data from adults aged 45 years and older with one or more chronic conditions who had at least one contact with their primary care practice. And get this, 19 countries. And this is a real range of countries.

They were looking at their experience of person-centered care measured using an instrument called the Person-Centered Coordinated Care Experience Questionnaire. They had almost 70,000 respondents with complete data nested within 1,600 primary care practices. With respect to their chronic conditions, the most frequently reported were hypertension, arthritis, cardiovascular disease, and diabetes. They had a primary care doc, or not. They also had a person in the office who was a care coordinator.

And what they found was that the factors that were associated with better patient experiences were having a relationship with their usual provider, and that was more than 5 years with their usual provider; a care coordinator who basically took a look at everything that was going on with them and transparently associated all of that so that everybody was apprised of it; and their alignment of the coordination responsibilities around those relationships.

And so it sounds to me like, in a way, this is sort of an obvious conclusion that if you have a long-term relationship with a primary care provider, a good care coordinator who’s transparent in coordinating all of that, that you’re going to end up feeling a lot happier about the care that you’re receiving.

Rick: It seems to make sense. I mean, in the past, when they’ve looked at clinical and utilization outcomes, it’s been primarily related to does it lower mortality, or does it reduce acute hospitalizations or after-hours use? Is there improved medical outcomes? But there’s really been comparatively little that has examined whether this continuity of care and how it’s coordinated actually shapes how the patient experiences it. And is it person-centered? On the one hand, you might say, well, this seems intuitive, but it’s really never been studied before.

Elizabeth: It’s kind of crazy, isn’t it, with all this noise we make about the patient voice, that it has been something that’s really been sidelined?

I do have a lot of respect for the conclusions that they draw with regard to health policy. They basically say, look, our study shows that this continuity and coordination can be delivered and sustained at scale. We need to figure out how we can do that.

They suggest patient registrations or list systems, trying to sustain workforce stability and retention, and interoperable information systems. And that, to me, also seems really critical because, as you know, here in this country, we have a multitude of different electronic health records that frequently do not talk to each other. Standardization of that seems really important to me.

Rick: This shows across a number of different countries — 19 different countries that coordinate medical care in different ways — when you reduce fragmentation and you kind of improve alignment with what the patient’s priorities are, you get better outcomes. On the one hand, you might say, well, we need to standardize. I think what this says is that this can be done in a number of different settings in different ways that medical care is delivered across the globe.

Elizabeth: Well, we certainly are looking forward to having more, at least, interoperable records so that somebody getting care in disparate places isn’t having to recreate the wheel every time they approach the healthcare system.

Rick: Yeah. My next study is also in the New England Journal of Medicine, and it’s about treating advanced breast cancer.

If we can screen and prevent late-stage breast cancer, the outcomes are much better. In early-stage breast cancer, treatment is so effective that the 10-year survival rate is over 95%, but in the later stages it’s as low as 50%. So we need to concentrate not only on prevention and screening, but also how do we treat those patients that have advanced breast cancer.

This was a study that looked in a phase III trial at a new agent targeting new pathways of individuals that are estrogen receptor-positive and HER2-negative that typically would receive standard therapy, and would target the estrogen receptor. They failed typical therapy, and then they went to the second stage, and the second stage involves what’s called a cyclin-dependent kinase. And unfortunately, after that, they failed that as well.

This is an agent called giredestrant. It targets the estrogen receptor, even though it may have [been] genetically modified. Because what happens is, oftentimes, there’s a mutation in that receptor so that it just goes bonkers, even without being stimulated by estrogen, and this particular agent can address even that.

So they took 373 women having advanced breast cancer. They had failed the two standard therapies, and they randomized them to receive standard endocrine therapy plus everolimus [Afinitor], or this new agent, giredestrant, plus everolimus. With standard therapy, the progression-free survival was about 5.5 months. With the addition of giredestrant, it increased to 10 months, but it was limited to those that had this mutation in the estrogen receptor. It happens about 40% of the time that individuals have failed both therapies. In this particular study, it was about 55% of patients.

Elizabeth: For me, at least, this begs the question of continuing to genotype a tumor as cancers progress, because clearly, they’re capable and do acquire additional mutations that then being able to target those specifically results in a clear benefit.

Rick: And as you suggest, those genetic footprints change with treatment. Either there’s a small population of cells that are resistant, and once we address the cells that are sensitive to chemotherapy, those cells grow. Or in the midst of therapy, a mutation arises. So the genetic footprint of these tumors changes over a period of time, and following that allows us to target therapy towards those particular mutations or receptor changes.

Elizabeth: Right. And I think it’s really great. I mean, this is a large number. Sometimes when we identify these particular mutations, they only impact like 10% of patients. But this is really a considerable percentage of the patients who had it.

Rick: Yeah. Four out of 10 patients that have already failed standard therapy. That suggests that a lot of individuals would benefit from this new therapy. You’re absolutely right.

Elizabeth: Let’s turn now to Nature Medicine. It’s an early-phase trial, but it really targets something that impacts an awful lot of people, and this is inhaled, small interfering RNA therapy that targets a particular receptor called RAGE [receptor for advanced glycation end products] in pulmonary inflammation.

So let me just remind everyone that pulmonary inflammation underpins these COPD and asthma. This RAGE is the receptor for advanced glycation end products. And this is a receptor that’s expressed in the lung alveolar type 1 cells, and it amplifies and sustains the innate immune response in, as I said, COPD and asthma, but also probably in other pulmonary disorders. So they developed this inhaled, targeted, small interfering RNA against that particular RAGE mRNA.

And what they showed, first of all, in a bunch of animal models was, yeah, this actually works out pretty well. And then in this, as I said, very early-stage trial in humans, they had healthy volunteers, 58 of them, and in patients with asthma, 19 of them, they were able to demonstrate that this inhaled ARO-RAGE was safe and well tolerated. They did not see any changes in their x-ray findings to their lungs, their pulmonary function tests, or systemic markers of inflammation in either of these cohorts. They also showed that the plasma levels of this were low, so it was consistent with the drug being retained in the lung. Per this idea of targeting specifically what’s going on and can we interfere with that is possible with this particular agent.

Rick: Yeah. And so this was interesting. As you mentioned, this is a phase I trial to identify whether this is safe and well tolerated. It targets RNA, and secondly, they attach it to a molecule that specifically incorporates it into lung cells. That’s why I think this particular therapy shows some promise. Typically, we treat these individuals with asthma or COPD with bronchodilators and prednisone immunosuppression, but there are a lot of people that break through. And being able to address this common final pathway, this RAGE pathway responsible for inflammation, does carry some promise.

Elizabeth: They do admit, of course, that they have not yet determined which specific types of asthma or COPD phenotypes are going to be the most responsive to this intervention. And that was an education for me. I didn’t realize that there were a multitude of phenotypes of both of those conditions.

Rick: There are. Well, some of them are inflammatory responses where there are primarily eosinophils involved. Some of them are primarily neutrophils involved. There are different pathways, both resulting in inflammation, but in different ways, which means that we probably need to address them differently.

Elizabeth: So on that note, that is a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.