Treating 'patient-centered problems' the next frontier in rheumatology
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Development of rheumatoid arthritis, or another such inflammatory disease, often brings with it a mental toll.
Battling through and managing constant pain can force unwelcome changes in a patient’s routine, especially one’s physical activity.
Studies frequently show higher instances of depression, fatigue and sleep loss in patients with RA.
However, recent research and treatment efforts signal a growing shift in our clinical approach to RA. Beyond just treating the disease from a biologic perspective, Leonard Calabrese, DO, director of the RJ Fasenmyer Center for Clinical Immunology at the Cleveland Clinic, told Healio that he sees a new focus on improving patients’ quality of life and mental health.
“I’m happy to say we’re entering a new era here where there is far more attention paid on what I like to call ‘patient-centered problems’,” Calabrese said. “The goal of taking care of rheumatoid arthritis, lupus or any such disease is not just to control the disease activity, but it’s to improve people’s quality of life. So we’re seeing, with emerging therapies, much more detailed studies of quality of life and labeling new therapeutic agents that can affect sleep and fatigue in addition to pain and disease activity.”
A biologic link
Studies often show a strong link between depression and RA, one that makes intuitive sense. However, the reason for such a link is a question that runs much deeper, and has become a focus of research among multiple inflammatory diseases.
“It’s actually a phenomenon across all inflammatory diseases, at least the major ones: psoriasis, psoriatic arthritis, inflammatory bowel disease, lupus and other allied conditions,” Calabrese said. “The question is more than just chicken and egg. Why is this such a common occurrence in all of these diseases?”
Calabrese said that recent studies led researchers to look beyond the idea that the link between depression and inflammatory disease is solely based off social adjustment and stress. Instead, research is beginning to target a potential biological factor.
“There’s an element of [social adjustment],” Calabrese said. “However, what we’ve found, and what data supports, is that in patients with inflammatory diseases and with the major depression itself, the most reliable biomarkers in the central nervous system are inflammatory mediators.”
A 2020 study published in Arthritis Care & Research indicated a previously unexplored biologic link between depression and rheumatoid arthritis, while a Belgian study published in February showed that patients with a high psychosocial burden are less likely to reach a sustained remission of RA.
Tackling fatigue
Among the symptoms linked with RA, Calabrese said fatigue stands out as one with an especially heavy impact on quality of life and mental health, and one that he expects to be a major focus of research in the near future.
“Fatigue is something that is in its ascendancy in people paying attention to it and prioritizing it,” Calabrese said. “For a long time, patients with rheumatoid arthritis have had significant fatigue as a population. Studies have shown that many patients value a day without fatigue as much as they do a day without pain. Fatigue can also be a difficult issue to broach between patients and practitioners, whether its primary care or rheumatology, because we lack quick fixes for this, and it’s frustrating for both parties. The patient feels unheard, the practitioner feels powerless, and we all share in this.”
Calabrese called fatigue research the “next frontier” in rheumatology, owing to its interrelation with other symptoms of both arthritis and depression.
“Fatigue doesn’t have a single cause, and it’s related to both behaviors and biologic systems,” Calabrese said. “In terms of behavior, it’s related to our physical activity level: people who are sedentary have more fatigue, and people who engage in moderate physical activity have less fatigue. People who have disturbed sleep, whether it’s quality or length of sleep, obviously have fatigue. Disturbed sleep is related to physical activity. And in terms of other associations, for people who are depressed, the two more common physical symptoms of depression are fatigue and pain.”
Calabrese hopes that recent developments will drive a more intense focus on fatigue in rheumatology research, namely the proliferation of studies on the effects of long COVID that have begun since the beginning of the COVID-19 pandemic.
“Now with COVID-19 a factor, people are paying so much attention to the syndrome of long COVID, where the dominating symptoms are fatigue, brain fog, musculoskeletal pain and so on,” Calabrese said. “Fatigue is in ascendancy as a complaint or a malady that’s widely spread throughout the population, and in particular the population of patients with rheumatic diseases, and now hopefully we’re going to come to a better understanding of this, because we’re doing a lot of creative research in that area.”
Unique approaches
These lines of inquiry are leading rheumatologists into some novel research directions. Calabrese said that studies are underway examining holistic wellness methods such as tai chi and the potential positive biologic impacts they may have on patients battling inflammatory diseases.
“We’re doing studies on rheumatoid and psoriatic arthritis right now and looking at different techniques, and talking about ramping up the research in mind/body techniques,” Calabrese said. “That’s using things such as qi gong and tai chi, which have been shown to be of value in many non-inflammatory diseases, but also have immune-modulating properties. Now is the time we can study it clinically, but also now look deep with immunologic profiling and immuno-autonomic studies, and try to find out how these techniques which have been used for thousands of years may actually be having a profound biologic effect.”
The willingness of researchers to pursue such questions is a development that Calabrese called “exciting,” and one that he hopes will go hand-in-hand with a renewed focus on quality-of-life treatment among rheumatology practitioners.
“It’s really a new era,” Calabrese said. “It’s moving from the research forum to the clinical forum, and I encourage all rheumatologists that using quality-of-life metrics in clinical practice is no longer a research technique. It should be done on everybody.”
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