The Influence of Multimorbidity on Rheumatoid Arthritis

Dr England discusses his study into the effects of multiple comorbidities on the achievement of targeted disease activity levels among patients with rheumatoid arthritis.

Bryant England, MD, 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:

RALN:

Welcome to this podcast from the Rheumatology and Arthritis Learning Network. I'm your moderator, Rebecca Mashaw, and today, I'm talking with Dr. Brian England, associate professor of medicine in the division of rheumatology at the University of Nebraska Medical Center and director of its Autoimmune Lung Disease Clinic. He and colleagues recently conducted a study into the influence of multimorbidity on achieving disease activity targets among patients with active rheumatoid arthritis. Thanks for joining us today, Dr. England.

Dr. England:

Well, thanks so much for having me.

RALN:

Your article in arthritis care and research mentions that you sought to assess the associations of multimorbidity with the odds of initiating a new DMARD in active RA, and the odds of achieving low disease activity or remission with that new drug. What sparked your interest in investigating this particular topic?

Dr England:

Well, I am a clinician investigator, so I spend a lot of my time doing research, but I also spent a lot of my time in clinical care with patients. And this project, and really my interest in multimorbidity in general, really came from what I was seeing at the bedside, that there's a growing prevalence of patients having multiple chronic conditions here, not only in the US but across the globe, and it makes treatment challenging as we try to manage rheumatoid arthritis in the context of other conditions that are transpiring. So that really sparked this interest of can we understand the other conditions that these patients have or their global multimorbidity, how that's affecting how both the patients and providers come together in clinic to make these treatment decisions, and then ultimately, how successful we are at managing this potentially debilitating disease.

RALN:

Your article also noted that your retrospective cohort study was conducted using the rheumatology Informatics System for Effectiveness or the RISE registry. Can you tell us a little bit about that?

Dr England:

Yeah, sure thing. So the American College of Rheumatology had this vision many, many years ago to develop this registry that could really guide research in rheumatology. And so what this is, is a registry that's based on electronic health records. There's over a thousand different rheumatology providers that are contributing data. It's growing every single day. At the time we did this study, there was over 2.4 million patients who were part of this registry. But these practices, they partner up with the RISE registry, they connect their electronic health record and they push their data to the ACR's RISE registry so that we can analyze the data and get insights from real world practices, and I think that part is really important when we think about multimorbidity.

A lot of our information we get on taking care of patients comes from clinical trials, but the patients in clinical trials are not just like the patients that we see when we knock on the door in clinic. They tend to be a little healthier and have very specific disease phenotypes. And so you end up with this conundrum where the evidence you're using to make treatment decisions is not necessarily coming from the patients that you're seeing. And multimorbidity is a prime example where if we want to understand how we're managing RA in patients with multimorbidity, we have to use real world data.

RALN:

Because so often, as I understand it, when patients are enrolled into a clinical trial, a lot of those multimorbidities are criteria that keep them out of the trial. Is that correct?

Dr England:

That's exactly right.

RALN:

Okay. So can you give us an overview of your study?

Dr England:

Yeah, sure thing. So we had 2 main questions, as you mentioned earlier. The first question was does multimorbidity influence whether or not we are going to add a new therapy or change to a new therapy in people who have active rheumatoid arthritis? Then the second question we had was a follow-up. If people are initiating a new disease-modifying therapy, does multimorbidity predict whether or not that initiation will be successful or not over follow-up? So within the ACR's RISE registry, we went and identified people who had persistently active rheumatoid arthritis. What that means is these patients were seeing their provider a couple of times. Their disease was not in low disease activity or remission at those consecutive visits. We used 2 consecutive visits because we felt it was important to really capture a group of patients that a treatment change was really needed.

We've all had times in clinic where someone's in moderate disease activity, you're not feeling well, but there may be another reason and we may decide that we are going to keep medicines as they are, give this a little bit more time, or maybe a medicine change has recently happened that needs a little more time to work. But by having 2 consecutive visits where these patients are not doing well, it's pretty clear, this is a population we should strongly be considering making a change to a new medicine. Then we looked at their disease activity levels after starting a new therapy for those who did initiate a new therapy and we classified how many of them over the next year were able to get into low disease activity or remission.

Now, we did this using 2 different RA disease activity measures. We used the RAPID3, which is completely composed of patient-reported outcomes measures, and we also used the Clinical Disease Activity Index, which takes information from both the provider and patients' global assessment of disease as well as 28 joint counts, both tender and swollen. Then we analyze the data, figuring out whether or not multimorbidity was predicting new treatment starts and their treatment success.

I do want to mention how we calculated multimorbidity because it's a little different in this study compared to many other studies of multimorbidity. Most of the time when we talk about assessing multimorbidity, we use diagnostic codes from an outpatient visit or a hospital encounter, either an ICD-9 or an ICD-10 code for a condition. Now, because of this registry, this registry is a single-specialty EHR, meaning we are only getting data from the rheumatologists. Well, rheumatologists don't always bill for all the other conditions that a patient may have, so that would lead us to really underestimating the multimorbidity of these patients.

What we did to address that is we used a multimorbidity index that is based on medications, because part of every clinical encounter is doing a medication reconciliation with the patient. So by looking through all of their medications, we could categorize them down to these different categories of potential conditions and then classify people on their multimorbidity burden based on the number of RX risk categories.

RALN:

So for instance, when you find a patient who is taking statins, then you have somebody who has got cholesterol problems, high cholesterol.

Dr England:

Exactly.

RALN:

Okay. So what were your findings? Was multimorbidity associated with initiating a new DMARD?

Dr England:

It was not actually, and that was a little bit surprising to us. In clinic, like I said, that was really what inspired this question. In clinic, it could be difficult, and sometimes, these patients who have multimorbidity, it's hard to find a medicine that has the favorable risk-to-benefit ratio. And so we were a little surprised to see that those with the highest burden of multimorbidity did not have any difference, the odds of initiating a new therapy.

The follow-up question though, we did see a very meaningful difference. So we saw that the patients who did initiate a new disease-modifying therapy, those with the highest burden of multimorbidity, about 30 to 40% lower odds of achieving their goal disease activity level, either low disease activity or remission, which is our target according to our pharmacologic treatment guidelines. So that's pretty significant that a third of these patients may not be reaching that goal because of their multimorbidity.

RALN:

Did you get any sense of what factors might be affecting that? Were there drug interactions that were causing a problem? Were some of these patients obese, and therefore, that can, I understand, cause difficulties in how they metabolize medications? What, if anything, did you conclude?

Dr England:

That's a great question. What is the mechanism of this finding? And that's something we couldn't completely determine from this study. I think what you mentioned, drug interactions, sure, that's absolutely a possibility. One of the other things that we have to consider is how we're assessing the outcome of treatment response, our disease activity measures, and we have a lot of data on their validity and their usefulness. They're great in clinical trials, but we do know that these measures aren't necessarily perfect. If how we're assessing our RA disease activity includes a global assessment, how overall, we feel, it absolutely has been shown that other conditions, fibromyalgia, osteoarthritis, other conditions can inflate those measures more than the 28-joint count does. So we can see somebody reporting that globally, they're not doing as well, even if they don't have a swollen joint.

RALN:

That's interesting, and that makes a lot of sense actually.

Dr England:

Absolutely. It's one of the additional challenges in practicing, taking care of RA in the real world setting versus a clinical trial.

RALN:

You mentioned in your findings that they indicated that a more holistic management approach targeting multimorbidity may be needed to optimize disease control for patients with active RA. How would you describe that holistic management approach? What do you think it should include?

Dr England:

Yeah. So this is difficult. I don't think we fully understand now what the best way to intervene and manage this is. I think the first step is just the general framework. Right now, I think sometimes we can get into a busy clinic, you have 15 or 20 minutes to interact with the patient and you can get pretty RA-centric for that entirety of that visit. So one change is taking this framework of remembering that the patient's not coming in, "I have RA and then all my other things." The patient's coming in and saying, "I have all of this." And that's the key point of multimorbidity, is that it's a patient-centric approach and RA is one of the things that that patient is bringing to the visit, and one of the things that when they leave, they're going to be managing and dealing with and experiencing life with. So I think taking a step back and remembering that we can't put on tunnel vision blinders for RA, but we have to think about the whole patient and everything that is contributing to their health and their wellbeing.

RALN:

So a multidisciplinary approach is important.

Dr England:

Absolutely, and I think there's a lot of ways we could potentially operationalize that. We don't really have any data to guide it, but whether that's involving other members of a health care team so that we can provide different approaches, perspectives. Whether that means we need to talk about goal setting with patients, and their goals may be a little different from somebody who has a lot of multimorbidity versus somebody who doesn't. Maybe our treatment targets need to be different. Maybe we don't push for remission as much in these people and we tolerate low disease activity. I think there's a lot of considerations like that that require us, again, to take that framework of we're patient-centric and RA is one of these different morbidities, that we're here to support the patient.

RALN:

Have you found among your RA patients what is often found in patients with autoimmune illnesses, that they can have more than one? That they may have multiple autoimmune conditions, not just additional problems with high cholesterol or weight or high blood pressure, but somebody with RA may also have another autoimmune illness of some sort?

Dr England:

Yes, absolutely. We see these autoimmune conditions cluster together, and some of that is there's some shared genetic basis for these different autoimmune diseases and maybe shared environmental risk factors, so absolutely we see that.

RALN:

And that would make it more complicated then to come up with an appropriate treatment plan for those patients?

Dr England:

Absolutely. It is always nuanced based on what type of other autoimmune condition they may have, but absolutely. One of the ways I like to think about multimorbidity is as a web and you have all these different morbidities that interact with each other, and what's happening is the patient gets trapped in this web. They get these morbidities, the morbidities interact, the morbidities all impact the patient directly, their interactions affect the patient. The patient's trapped in this web and we need to figure out how to manage them, get them through this so they don't have the complications being trapped in the web.

RALN:

So what advice would you offer to practicing rheumatologists about ways to improve outcomes for patients like this in that 15-, 20-minute visit, in the context of a busy clinical practice? What can they do?

Dr England:

A first step is recognizing that the person is multimorbid, and we do a pretty good job, I think, of taking detailed histories and physicals as a rheumatologist and keeping problem lists with what's going on in our patients. And I think just taking a step back and remembering, when we see that problem list, that problem list has 3, 4, 5, 6, 7, 8, 9, 10 things on it. Okay, step back for a second. Realize this patient's multimorbid. They're coming here with many different morbidities occurring. We need to support them through all of these. Absolutely, we're going to target RA, but it's just a reminder to us to take that step back and think about the big picture. Don't lose the forest through the trees.

RALN:

Got it. Well, we appreciate your time today. This has been very interesting and we'll look forward to talking with you again, seeing what else you discover in future research.

Dr England:

All right. Thanks so much for having me.