ACR Convergence 2024—With poor sleep a major complaint among patients with rheumatologic diseases, physicians should hone their understanding of how the body regulates sleep and how this system can be disrupted, and tailor their management plans to help patients with these issues, panelists said in a session at ACR Convergence.
Dr. Kim
For some patients, their struggles with getting quality sleep couldn’t be more apparent—he has seen patients asleep as he enters the exam room during office visits, said Alfred Kim, MD, PhD, associate professor of rheumatology at Washington University.
Light is the main trigger and input for nearly all of the circadian rhythms of the body—prompting melatonin production, lowering body temperature and other changes that promote sleep. In fact, the suprachiasmatic nucleus part of the hypothalamus—which controls the body’s “central circadian rhythm”—has only one input and it’s from the retina. In other words, light, Dr. Kim said.
The body’s circadian rhythms are essentially regulated by the accumulation and degradation of proteins produced by the body’s “clock genes,” including clk, tim, per and bmal1. From there, the peripheral circadian rhythms are dictated by the central circadian rhythms but are additionally influenced by liver activity determined by when we eat, and by exercise, he said.
“‘I’m bringing this up because a leading risk factor for cardiovascular events in humans is discordance between central and peripheral circadian rhythms,” he said. “A leading cause of mortality in our rheumatic disease patients is cardiovascular events.”
Glucocorticoids can reset the body’s peripheral circadian rhythms, so the timing of these medications might be very important, he said. What’s more, he said, sleep is a learned behavior. Therefore, “you can unlearn it,” associating sleep cues with increased attention to pain and actually prompting a drive to avoid sleep, he said.
Correlations with Rheumatic Disease
A study out of Taiwan found that patients with lupus who had non-apnea sleep disorders had an increased risk of acquiring lupus or rheumatoid arthritis.1
In a study on which Dr. Kim worked, researchers found that if a patient had a score above a threshold on a sleep-related patient-reported outcome (the Sleep-Related Impairment scale, or SRI), they had a higher risk of having a clinically meaningful deterioration at the next visit. When comparing patient-reported outcomes to objective actigraphy measures, though, researchers found poor correlation between them, which should prompt the question of what is really being measured with the SRI, he said.2
Dr. Katz
In rheumatoid arthritis, sleep quality and rheumatic disease are frequently intermingled, said Patti Katz, PhD, professor of medicine at University of California, San Francisco.
A study of survey data from the FORWARD cohort of 4,200 RA patients found that a high risk of obstructive sleep apnea (OSA) or a diagnosis of OSA was prevalent in about 21% of the cohort, with 31% reporting restless leg syndrome.3
Short sleep of less than seven hours per night was seen in about three-quarters of the patients, and short sleep of less than 6 hours was seen in 43%.
In the RAZZ study, led by Dr. Katz, 116 patients were measured using actigraphy and 63 were measured with WatchPAT, which can produce an apnea-hypopnea index (AHI), a measure of OSA. Researchers found that more than 50% had moderate to severe OSA, but only about half of those patients had an actual OSA diagnosis. The study is not yet published.
Difficulties with sleep were very common. At baseline, over half had poor sleep efficiency, the ratio of time asleep versus the time in bed trying to sleep. Seventy percent had poor sleep efficiency—which can affect both the total time sleeping and the quality of sleep physiologically—at some point during the study, and more than 40% had poor sleep efficiency at every time point measured.
Among the WatchPAT cohort, almost everyone had either short sleep, OSA or low sleep efficiency; only 3 of 58 had none of those.
“This is a real problem,” Dr. Katz said.
In the study, researchers found the suggestion of an effect of OSA and ESR levels, and a clear effect on IL–6, when comparing those with and without moderate to severe OSA. They didn’t find a link between low sleep efficiency and RA when looking at single measurements at baseline, but among those who had poor sleep efficiency at any time point, they saw higher Clinical Disease Activity Index (CDAI) scores.
Sleep Management Tools
Dr. Lee
When trying to help patients with rheumatic diseases with their sleep struggles, there are a lot of ways a physician can approach it, said Yvonne Lee, MD, MMSc, associate professor of medicine at the Northwestern University Feinberg School of Medicine. Treating the inflammatory disease activity, minimizing medications that can disrupt sleep, treating patients’ comorbidities and treating the sleep problem itself are all worth consideration, she said.
“Sleep is obviously a very multi-factorial problem, and so when we come to think about managing sleep, it often requires a very individualized and often multi-modal strategies,” she said.
Studies of drugs like certolizumab and tofacitinib have found that treatment helped lead to improved sleep quality. But the association between an improvement in disease activity itself, and the quality of sleep, was only low to moderate, she said.4
“I think there is a relationship but there are also other mechanisms here,” Dr. Lee said.
Studies of glucocorticoids and sleep have found mostly a linear relationship—as the dose goes up, sleep disturbance goes up, she said. But when it comes to the duration of use, researchers have seen a threshold effect—duration only seems to matter among patients taking the equivalent of at least 7.5 mg of prednisone daily.5
Managing comorbidities can be important, she said. Depression might be particularly important—studies have found that elevated disease activity is associated with greater sleep disturbance among non-depressed patients, but that sleep disturbance remained constant despite differences in disease activity among depressed patients, Dr. Lee said.6
In terms of managing sleep itself, Dr. Lee said, “I really, really want to emphasize the importance of non-pharmacologic sleep strategies here. This really should be the foundation of how we manage sleep.”
Many of these approaches are fairly well known—consistent sleep times, staying off phones shortly before sleep and increasing exercise.
Research on cognitive behavioral therapy (CBT) and sleep has seen mixed results. In one study involving six face-to-face sessions on topics such as sleep hygiene and stimulus control, there was no difference on sleep efficiency measured by polysomnography.7
But patient-reported insomnia did improve to a clinically significant degree, Dr. Lee said. Comments by patients give a sense of how the sleep-education component of CBT can have a positive effect, she said.
“The patients really talked about how they kind of knew some of these things before, but having someone talk to them about it and drive it home was really important.”
Thomas Collins is a freelance medical writer based in Florida.
References
- Hsiao Y-H, Chen Y-T, Tseng C-M, et al. Sleep disorders and increased risk of autoimmune diseases in individuals without sleep apnea. Sleep. 2015 Apr 1;38(4):581–586.
- Chu P, Ju YS, Hinze AM, et al. Measures of sleep in rheumatologic diseases: Sleep quality patient-reported outcomes in rheumatologic diseases. Arthritis Care Res (Hoboken). 2020 Oct;72 Suppl 10(Suppl 10):410–430.
- Katz P, Pedro S, Michaud K. Sleep disorders among individuals with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2023 Jun;75(6):1250–1260.
- Bartlett SJ, Bingham CO, van Vollenhoven R, et al. The impact of tofacitinib on fatigue, sleep, and health-related quality of life in patients with rheumatoid arthritis: A post hoc analysis of data from phase 3 trials. Arthritis Res Ther. 2022 Apr 5;24(1):83.
- Curtis JR, Westfall AO, Allison J, et al. Population-based assessment of adverse events associated with long-term glucocorticoid use. Arthritis Rheum. 2006 Jun 15;55(3):420–426.
- Hughes M, Chalk A, Sharma P, et al. A cross-sectional study of sleep and depression in a rheumatoid arthritis population. Clin Rheumatol. 2021 Apr;40(4):1299–1305.
- Latocha KM, Loppenthin KB, Ostergaard M, et al. The effect of group-based cognitive behavioural therapy for insomnia in patients with rheumatoid arthritis: A randomized controlled trial. Rheumatology (Oxford). 2023 Mar 1;62(3):1097–1107.
