Elena Myasoedova, MD, PhD, on Extra-Articular Manifestations in Rheumatoid Arthritis

Dr Myasoedova reviews recent research showing that extra-articular manifestations of rheumatoid arthritis are on the decline.

Elena Myasoedova, MD, PhD, is an associate professor of medicine at the Mayo Clinic in Rochester, Minnesota.

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, its employees, and affiliates.

Welcome to this podcast from the Rheumatology an Arthritis Learning Network. I'm your host, Rebecca Mashaw. And today, I'm joined by Doctor Elena Myasoedova, an associate professor of medicine and epidemiology and chair of the inflammatory arthritis specialty group at the Mayo Clinic in Rochester, Minnesota. She's going to talk to us about her recent research into the decline in incidence of extra-articular manifestations of rheumatoid arthritis.

Thanks for joining us today.

Dr Myasoedova:

Thanks for having me.

Rebecca Mashaw:

So why did you pursue this subject for your research?

Dr Myasoedova:

Well, extra-articular disease manifestations of rheumatoid arthritis are very common, and they are very impactful to patients' life and well-being. They may affect virtually every organ and system, and they have significant association with morbidity and mortality. The study is actually a part of a series of studies evaluating trends in incidence of rheumatoid arthritis in a well-defined population using our population-based inception cohort of patients with rheumatoid arthritis residing in Olmsted County, Minnesota. As there have been notable changes in epidemiology of rheumatoid arthritis and management of rheumatoid arthritis in recent decades, we aimed to evaluate the changes in incidence of extra-articular manifestations of rheumatoid arthritis and its association with mortality in rheumatoid arthritis as we hypothesize that the changes in epidemiology and treatment have affected the incidence and association with mortality of extra-articular rheumatoid arthritis as well.

Rebecca Mashaw:

Would you give us a brief overview of your study and its structure?

Dr Myasoedova:

Definitely. The study included an incident cohort of patients with rheumatoid arthritis who fulfilled 1987 classification criteria for rheumatoid arthritis between 1985 through 2014 and included a cohort of 907 patients. Patients were grouped into 2 cohorts based on RA incidence date. The first cohort was 1985 to 1999, and second cohort was 2000 to 2014. The year 2000 was chosen a priori as there were significant changes in management that occurred around that time and were hypothesized to affect extra-articular rhematoid arthritis. And then patients were followed up for a median of 8 years for the development of extra-articular disease.

Rebecca Mashaw:

Were there specific extra-articular manifestations that you looked for or assessed in this study?

Dr Myasoedova:

Yes. Certainly. To ensure comparability with ascertainment of extra-articular manifestations between the 2 cohorts, we used an existing classification of extra reticulum manifestations that was proposed previously by Dr Carl Thoreson. Extra reticle manifestations that we evaluated ranged from nonsevere manifestations such as, for example, subcutaneous rheumatoid nodules to severe, such as rheumatoid vasculitis. There were a total of 19 manifestations that we evaluated.

Subcutaneous rheumatoid nodules were by far the most common manifestation, while cases of rheumatoid vasculitis were very rare. And other manifestations included keratoconjunctivitis, sickle, pericarditis, pleuritis, interstitial lung disease, among others.

Rebecca Mashaw:

What were the results of your study?

Dr Myasoedova:

We found that the 10-year cumulative incidence of any extra-articular manifestation has decreased significantly between the early and later cohorts. And this was largely driven by significant declines in subcutaneous rheumatoid nodules and nonsevere extra-articular manifestations. We identified risk factors for the development of patients of rheumatoid arthritis and those included being positive for rheumatoid factor as well as current smoking. We identified increased mortality associated with either nonsevere or severe extra-articular manifestations.

Rebecca Mashaw:

I think you already answered my next question, which is were some clearly more common than others? You mentioned the nodules being the most common. Were there others that you saw frequently in the course of this study?

Dr Myasoedova:

Yes. The other frequent one was keratoconjunctivitis sicca, or sicca manifestations involving eyes and oral cavity.

Rebecca Mashaw:

How did you define severe versus nonsevere in this context?

Dr Myasoedova:

So, like I mentioned, the classification that was previously used applied here. And severe is generally defined as manifestations that have most impact on morbidity and mortality. So associate with worse outcomes, primarily in terms of, risk of death.

Rebecca Mashaw:

Did you arrive at any hypothesis about why these extra-articular manifestations are decreasing overall?

Dr Myasoedova:

Yeah. We, we debated several, possibilities, and I think that the reasons are likely several-fold. The implementation of early and effective treatments, the disease modifying antirheumatic drugs, as well as widespread use of biologics and the approach that was implemented, which is called treat to remission, have resulted in improved control of rheumatoid arthritis disease activity and decline in severity of rheumatoid arthritis after 2000. Changing role of environmental risk factors such as decline in smoking rates as well as increasing rates of obesity, as well as shifts in autoimmune footprint of rheumatoid arthritis, including decline in rheumatoid factor positive and cyclic citrullinated antibody positive rheumatoid arthritis, an increase in seronegative disease, can be also contributing. In fact, seropositivity and smoking associate with over 2-fold increase in risk of extra-articular manifestations, particularly rheumatoid nodules. So it makes sense that as these factors are declining in population, the incidence of these manifestations are is also coming down.

Rebecca Mashaw:

It's particularly interesting that although these manifestations are decreasing, mortality is increasing among patients who do manifest these conditions. You've mentioned some things that that factored into your assessment. But did your research give you any clear clues about why this might be the case? Is it about the general severity of the rheumatoid arthritis, do you think?

Dr Myasoedova:

Thank you for asking this question. It is important to interpret the findings correctly. While extra-articular disease incidence is decreasing, the association of extra-articular manifestation with mortality has not changed over time. This means that extra-articular rheumatoid arthritis is becoming more rare. But if present, it carries a substantial over 2-fold increased risk of mortality as these manifestations generally signify a more severe disease.

Rebecca Mashaw:

So do you plan to expand your research into this area? What's next?

Dr Myasoedova:

Certainly. The most pressing need is in studying rheumatoid arthritis-associated interstitial lung disease. This presentation is common. It is a major contributor to mortality, and it has seen no decline in incidence. And it has scarce therapeutic options. There's been a lot of research done in this area, and it is being pursued by our group and others.

Rebecca Mashaw:

Any thoughts for your colleagues in rheumatology about how your study results might be applied in their clinical practice?

Dr Myasoedova:

I think this study has important clinical implications. And the main implication is that of increased mortality risk associated with extra-articular rheumatoid arthritis. Even though the extra-articular manifestations are becoming less common, rheumatologists should remain vigilant while evaluating a patient and look for any possible extra-articular manifestation because their presence may raise a concern for worse outcomes and may require more aggressive treatment.

Another implication is that, overall, since extra-articular disease is on decline after the year 2000, it means that the strict management and the use of targeted therapies generally benefit the patients. So that's good news.

And the third implication is that rheumatoid arthritis-associated interstitial lung disease, unfortunately, is not declining, which is unlike many other extra-articular manifestations of rheumatoid arthritis, and it remains a challenge requiring further efforts from rheumatologic community, Both on the research side as well as on clinical practice side.

Rebecca Mashaw:

Well, we appreciate you taking the time to talk with us today, and we'll Look forward to any continuing, research and results that you produce. Thank you.

Dr Myasoedova:

Thank you. Thanks for having me.