Multimorbidity Among Patients With RA

Dr Bryant England gives us the key points from his study on whether certain multimorbidity patterns are associated with long-term disease severity among patients with rheumatoid arthritis.

Bryant England, MD, PhD, is associate professor of medicine in the Division of Rheumatology at the University of Nebraska Medical Center, and director of its Autoimmune Lung Disease Clinic in Omaha, Nebraska.

TRANSCRIPT:

Any views and opinions expressed are those of the authors and/or participants, and do not necessarily reflect the views, policy or position of the Rheumatology and Arthritis Learning Network or HMP Global, their employees, and affiliates.

Welcome to this podcast from the Rheumatology and Arthritis Learning Network. I'm your moderator, Rebecca Mashaw. Today I'm speaking with Dr. Bryant England, who is an associate professor in the division of rheumatology at the University of Nebraska College of Medicine in Omaha, and the Veterans Administration Nebraska-Western Iowa Healthcare System. He and his colleagues recently conducted a study on whether certain multimorbidity patterns are associated with long-term disease severity among patients with rheumatoid arthritis. Thank you for taking the time to talk with us today about your study, Dr. England.

Dr. Bryant England:

Well, thank you so much for having me.

RALN:

What made you choose this topic for research?

Dr. Bryant England:

Well, this is really driven by the interactions that I have in clinic. Clinically, when I see patients, I've noticed that the majority of them have other conditions besides rheumatoid arthritis that affect how we are managing the disease. And certainly, when we've looked previously in large epidemiologic studies, we find that the data fits with what we see in clinic, that overall at a population level, most patients with rheumatoid arthritis have other chronic diseases that are part of how we identify and manage these conditions.

RALN:

Can you give us a brief overview of your study? How many participants, how the study was structured, just the basics?

Dr. Bryant England:

Absolutely. We conducted a cohort study, meaning that we identified about almost 3,000 people with rheumatoid arthritis, and they enrolled in this registry from a number of different VA sites across the country. We followed them over time, collecting disease activity measures and functional status as part of the regular care visits.

What we did is, at the time that they entered into the registry, we looked into the medical records and we identified all these other conditions that patients may be experiencing. And from those conditions, we then apply these multimorbidity patterns that we've previously derived. Because as you can imagine, there's a long list of other conditions that people can develop. And so there's a lot of combinations that can happen. But previously we've shown that there's really about 4 primary patterns of multimorbidity that tend to affect people with rheumatoid arthritis. So we identified the conditions, applied those patterns, and then determined whether those patterns, at the time they enrolled, could predict how their disease activity and functional status was going to be over the next 5 years of follow up.

RALN:

What specific multimorbidity patterns did you include in this study?

Dr. Bryant England:

The 4 patterns that we assessed, we assessed metabolic multimorbidity, chronic pain multimorbidity, mental health and substance abuse multimorbidity, and cardiovascular multimorbidity. Now, we did some additional analysis of slight variations of these based on how we had derived these previously, but those were the main patterns we assessed.

RALN:

And how did you measure their effects on patient quality of life and functioning?

Dr. Bryant England:

As I mentioned earlier, at the time they came into our clinics for routine clinical care their treating rheumatologists would score their disease activity. And we looked at this with a couple different measures, but the primary measure that we used was the DAS28, and then we measured functional status at the same time using the Multidimensional Health Assessment Questionnaire.

RALN:

And what did you find?

Dr. Bryant England:

Well, what we found was that several of these patterns were associated with higher disease activity and poor functional status, not only at the time that they were enrolled, but even throughout up to 5 years of follow-up. We observed this with chronic pain, with mental health and substance abuse, and with cardiovascular multimorbidity. The only pattern of multimorbidity that we didn't see associated with poor functional status and disease activity was the metabolic pattern of multimorbidity.

RALN:

So can you explain what that metabolic pattern includes, and did you come to any conclusions about why it does not have the same effect as the other patterns that you included in the study?

Dr. Bryant England:

Absolutely. The metabolic pattern of multimorbidity includes several different conditions that are related to metabolic disturbances. Not surprisingly, this includes diabetes, this includes obesity. It also includes hyperlipidemia, hypertension, sleep disorders, renal disorders— tended to cluster together with those. Now while you may say that the pathogenesis of a sleep disorder is not necessarily metabolic, that is true, but it tends to associate with these other metabolic disorders. And that's the idea of these patterns, is it moves beyond everything individually and it thinks of what conditions tend to group together. And so the best overall label for these conditions is that it's a metabolic derangement that kind of group these conditions.

Now in our cohort, this was a highly prevalent pattern of multimorbidity. Over 60% of the people in our cohort, they had metabolic multimorbidity. So I think that, why was metabolic not associated? It doesn't necessarily mean that metabolic derangements don't contribute to function or they don't contribute to disease activity, but rather I think that the majority of our patients have this so it's harder to tease out that there is a difference by having it.

The other piece is that it's a pretty broad category. And so if you looked individually at obesity, we know that obesity tends to be associated with higher inflammatory markers. So I think looking at this more globally versus a very specific metabolic condition could also affect why we may not have seen that.

RALN:

Did any of the patterns that you studied have a greater impact than others? Was there one predominant pattern? And you just mentioned metabolic didn't affect the functioning as much and for the reasons that you described, but the ones that did, did you see any difference in how prevalent that pattern was among your patients?

Dr. Bryant England:

Yeah, so there was a little bit of difference in terms of the prevalence. The chronic pain and mental health patterns were a little bit more prevalent than the cardiovascular. In terms of their impact on function and disease activity, we didn't formally compare them to each other, but overall we tended to see that they had highly overlapping estimates for how different they were, versus not having that pattern.

Where we really saw the biggest difference in terms of magnitude was when we took a step back even from the patterns and said, "Okay, let's not look at the individual pattern, but let's look at this idea of, does the number of patterns of multimorbidity you have matter?" And so when we looked at people who had no multimorbidity patterns versus 1, 2, 3 or all 4, we saw a very clear dose response, where the more number of multimorbidity patterns you have, the more it was impacting function, the more it was impacting disease activity.

And I think that's a really important thing as we start to think about what is multimorbidity. It's not just the score, it's not just the count of a number of conditions, but when we think about it broadly here, these are independent patterns. So patients are having things that put them in this pattern and that pattern and a third pattern. Now we're clearly seeing an impact or an association with how their disease is manifesting.

RALN:

It's easy to see, for instance, how chronic pain would affect poor functional status, but how does cardiovascular health or mental health actually affect RA disease activity? Were you able to determine anything about that?

Dr. Bryant England:

That's a great question. We did some analysis to try and look at that a little further. One of the things we did was when we looked at disease activity, disease activity is typically measured with a composite measure. So we looked at the individual components of these disease activity measures to see if certain patterns were associated more closely with different aspects of these composite measures. And indeed, we saw that the chronic pain or the mental health and substance abuse patterns, we saw that there was a strong association with tender joint counts or with patient global assessment scores.

Now when we've looked at the cardiovascular pattern, we saw that here there were stronger associations with swollen joint counts or inflammatory markers. And now this doesn't tell us anything about a mechanism, but it does point us down the road that yes, the pattern and how it is associated with function and disease activity may depend on the individual components. So it's a little more specific than a more global disease activity and function.

I think the other important point is that this isn't necessarily a unidirectional relationship. And by that I mean, we don't necessarily say that these multimorbidity patterns are causing the disease activity or function to be worse, but rather, it's more that this is a global ... How a person feels is related to rheumatoid and these other things, and they're probably interconnected. We know rheumatoid arthritis is associated with a higher risk of developing cardiovascular disease, of mental health, of metabolic derangements. But then is it possible by having those, it also makes the disease presentation manifestation even more severe over time? So it's closely interconnected more so than a clear XY relationship.

RALN:

So you're looking at it really from a holistic perspective?

Dr. Bryant England:

Exactly.

RALN:

That's very interesting. You also noted that identifying and addressing these multimorbidity patterns, of course, can help patients achieve RA treatment targets. For the practicing rheumatologists who will listen to this podcast, how would you advise them to go about identifying these patterns, and then how can they address them effectively with their patients?

Dr. Bryant England:

It starts really with ... Following a treat-to-target approach means we have to measure our disease activity. And after we measure our disease activity, then we have to consider whether a change of therapy is warranted. As I'm practicing and thinking about this in clinic with patients, where I think it really starts is at that point of interpreting your disease activity measure. You may see a patient who's telling you and from what they're telling you, it seems like their symptoms are pretty well controlled in terms of how their joints are doing. You may examine their joints and their joints are doing well, but you may still notice that they're still having quite a bit of tenderness. They're still rating their overall disease as not doing very well. And then this has been described before in the literature, some discordance here.

And I think taking a close look at what other conditions are going on is a really important way of getting you, the provider, and your patients together on the same page, of what is really driving these scores. And helping them understand that maybe that pain score is really being driven by the chronic migraines you've been having and it's not necessarily the rheumatoid. And so in that situation, it may not have the best risk-to-benefit ratio to escalate their disease-modifying therapy or change their disease-modifying therapy, but rather we need to go down a different route of how can we better manage your migraines so that your overall general health is doing better and you may be able to process pain better as a result.

RALN:

For the rheumatologist who's working, for instance, in an academic center, as you do, they may have easy access to the specialist who could help them, the neurologist who could help them with the patient who's got chronic migraine, or the cardiology department who can help them in managing the patient's cardiovascular disease. What about the rheumatologist who doesn't have all of those things easily at hand? How would you advise them to go about pursuing this sort of ... It's really a multidisciplinary approach that you're talking about?

Dr. Bryant England:

Yeah, absolutely. It'd be ideal if we could all have a multidisciplinary clinics here, and as patients came in we could help them get to the right people with the expertise in real time. Unfortunately, that's not real practical to implement more broadly.

But one of the things that I always really try and talk to my patients about is the importance of having a primary care provider. Sometimes with rheumatology, because we are managing chronic diseases, patients will look to us as experts who've really helped them through a difficult time, and they may come to see us almost like a primary care provider. And so I think it's really important to educate patients that, "Hey, I know we may see each other every 3 months and we may try and help you beyond your rheumatoid, absolutely, we want to help you feel better globally."

But I explain to them it's really important to have the quarterback of your team, and that quarterback of your team is the primary care provider. They have general medical expertise that we may not feel as comfortable with anymore. And so getting them involved and making sure they're aware of their role and value I think is really important.

RALN:

So the primary care physician becomes more, as you said, the quarterback or the gatekeeper. And yes, the rheumatologist is going to deal with your RA, "But here's a recommendation for a cardiologist who can help you make sure that you've got your cardiovascular disease under control, and to help you with lowering your cholesterol and lowering your blood pressure."

Dr. Bryant England:

Exactly. And sometimes we even find situations as we're thinking about treatment changes for the rheumatoid arthritis. We think that, "Well, in the context of other things going on in your health, this may not be the right time or the right decision to do." And so that's where it's really valuable to reach back to the primary care and communicate why you're making these decisions and what sort of overall general medical management could be really impactful for allowing us to maybe make that RA decision down the road to improve their outcomes.

RALN:

Any last thoughts for your colleagues in rheumatology when it comes to helping patients with multiple morbidities?

Dr. Bryant England:

I think we still have a ways to go. I don't know that we have the best approach for how to manage rheumatoid arthritis and multimorbidity together. Certainly as we think about the clinical trials that generate a lot of our evidence, patients with multimorbidity probably aren't comprising most of those people in the trials so we are lacking some evidence here.

But I think just really assessing each patient and thinking in the context of, what are the other factors? What are the other conditions contributing to their overall health right now? How might those relate with rheumatoid arthritis and how can we make sure we're doing the best thing, not just for their joints, but for them as a person.

RALN:

Well, thanks very much for spending this time with us. It's very interesting and I look forward to talking to you again.

Dr. Bryant England:

Sounds great. Take care.