George Karpouzas, MD, on the Factors Affecting RA Medication Adherence

In this podcast, George Karpouzas, MD, talks about his study that evaluated the influence of distinct domains of rheumatoid arthritis (RA) disease activity, functional limitation, mood disturbance, as well as RA-specific knowledge and patients’ beliefs about medications on treatment adherence.

Additional Resource:

• Karpouzas GA, Hernandez E, Ruiz L, Strand V, Ormseth SR. Role of clinical impact, disease-specific knowledge and beliefs about medication on therapeutic adherence in rheumatoid arthritis: an integrative structural equation modeling approach. Paper presented at: American College of Rheumatology 2019; Atlanta, GA; November 8-11, 2019. https://acrabstracts.org/abstract/role-of-clinical-impact-disease-specific-knowledge-and-beliefs-about-medication-on-therapeutic-adherence-in-rheumatoid-arthritis-an-integrative-structural-equation-modeling-approach/

George A. Karpouzas, MD, is a professor of medicine at the University of California, Los Angeles, and chief of rheumatology at The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center in Los Angeles, California.

TRANSCRIPT:

Amanda Balbi: Hello everyone, and welcome to another installment of Podcasts360—your go-to resource for medical news and clinical updates. I’m your moderator Amanda Balbi with Consultant360 Specialty Network.

Treatment of rheumatoid arthritis to remission optimally ensures control of symptoms, prevention of structural damage, and optimization of function and quality of life. Adherence to medical treatment is, therefore, critical for comprehensive and successful management of RA.

In a new study, a research team evaluated the influence of distinct domains of RA disease activity, functional limitation, and mood disturbance, as well as RA-specific knowledge and patients’ beliefs about medications on treatment adherence.

Today I’m speaking with the lead author of the study, Dr George A. Karpouzas, MD, who is a professor of medicine at UCLA and chief of rheumatology at The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center in Los Angeles, California.

Thank you for joining us today, Dr Karpouzas. Let’s dive into your study.

To start, can you tell us more about the proposed model you used to evaluate the impact of disease activity, functional limitation, mood disturbance, and RA-specific knowledge among patients with RA?

George Karpouzas: Thank you, Amanda Of course. Specifically, we evaluated 285 patients with established RA from our center. We set up the model in which we alleged that disease activity as measured by DAS 28 CRP, mood disturbance, and functional limitations, as well as RA-specific knowledge would be expected to predict beliefs patients had about necessity of medication, some concerns about them, which in turn would impact their adherence to such medications.

Amanda Balbi: How does RA-specific knowledge influence treatment adherence?

George Karpouzas: That’s a good question. You would assume that knowing more about your disease-specific medications—some of the medications you were talking—would foster your ability to understand that you need them and basically would foster your adherence.

However, what we quickly found out is that RA-specific knowledge in our model was not significantly associated with either medication beliefs or adherence, and therefore, it was quickly dropped out of our model. Now there's quite a few reasons for that.

Now the classic patient knowledge questionnaire, which is standardized and is still in use, is antiquated. It was basically formed in the mid-1990s, and many of the questions that are in that questionnaire, are no longer relevant, if you will. There are questions about medications in there that are not even used in our current armamentarium, like penicillin.

There's a ton of questions about NSAIDs, and there's no questions about biologic DMARDs, which are basically one of the mainstays of treatment of this disease. Therefore, because many of those questions were technically antiquated and perhaps obsolete, we found really no relevance of RA-specific knowledge, as it pertains to those in our model. So that was completely dropped.

Amanda Balbi: How do distinct domains of RA, such as disease activity, functional limitation, and mood disturbance, impact clinical outcomes and medication adherence?

George Karpouzas: Our assumption was that all those parameters would culminate into better adherence. So after the specific knowledge about RA was quickly dropped, then different modifications that we applied to our model allowed us to suggest the addition of 2 additional paths.

One was from mood disturbance to adherence in patients treated with conventional synthetic DMARDs, and a second path from disease activity to adherence in patients taking biologicals. The addition of those 2 paths basically improved the goodness of fit of our models and yielded more meaningful results.

To that end, what we found was disease activity … First of all, mood disturbance and functional limitation collectively representing salient components—as I mentioned earlier, this clinical impacts of RA—are all significantly correlated, meaning disease activity adversely impacted mood directly and functional ability, both directly and indirectly, through mood disturbance.

Additionally, mood disturbance directly worsens functional limitation, which is not really a surprise. Now we also found that disease activity, functional limitations, and mood disturbance influenced adherence via multiple and often competing pathways, both directly and indirectly, through a necessity concerns evaluation and appraisal by patient. So, RA activity directly, for example, promoted adherence in some patients with biologic DMARDs.

Now in contrast to that, in patients with conventional synthetic DMARD treatment alone, RA activity had an indirect net negative effect on adherence. The main pathway was through worsening mood disturbance, which in turn attenuated adherence.

What this means is that the experience of disease activity in patients who take biologicals may be sufficiently impactful to independently promote medication adherence. By contrast, disease activity in those who only take conventional synthetic DMARDs, maybe largely experienced as depressed mood, which may in turn overwhelm their capacity to adhere.

The other thing we found is that mood disturbance adversely influenced adherence directly in patients unconventional synthetic DMARDs, yet there was no significant direct or indirect effect of mood disturbance on adherence to biologicals.

Lastly, functional limitations fostered adherence through enhanced awareness of medication necessity.

Amanda Balbi: Were there differences in patients treated with biologic DMARDs vs conventional synthetic DMARDs?

George Karpouzas: As you know, there is a precedent in the literature for wanting to examine those patients separately, because clearly there's emerging data from biologic trials. But biologicals perhaps have superior effects on moderating mood in patients with rheumatoid arthritis compared to conventional synthetic DMARDs.

So what we also found—through our modeling that created empirical evidence to support that and therefore we examine those models separately—is that the type of medication treatment, meaning biologic DMARDs vs conventional synthetic DMARDs, may in fact moderate the effect of disease activity on mood disturbance.

Basically, what we found is that the difference between bDMARDs and conventional synthetic DMARDs on that path was actually significant, especially when we used time-averaged disease activity to evaluate this.

So, that's why it's important to examine those things separately. It appears that biologic DMARDs have this salient difference compared to conventional synthetic DMARDs in moderating the effect of disease activity or mood disturbance.

Amanda Balbi: What is the overall key take-home message from this study?

George Karpouzas: The message should be that distinct domains of clinical impact of rheumatoid arthritis influence treatment adherence directly or indirectly through a necessity concerned framework applied by the patient when they make that decision.

So, mood disturbance or concerns about medication may be complimentary yet salient intervention targets for a comprehensive RA management, promoting medication adherence.

The former, meaning mood disturbance, may be more relevant for patients on conventional synthetic DMARDs, whereas the latter, may be more significant for patients who are treated with biologic DMARDs.

Amanda Balbi: Absolutely. Thank you again for speaking with me today, Dr Karpouzas.

George Karpouzas: Thank you very much, Amanda, for this opportunity to communicate our findings to the broader rheumatology audience.