Poor sleep quality is very common among patients with relapsing-remitting multiple sclerosis (RRMS) or clinically isolated syndrome (CIS), and is associated with a lower quality of life, and greater fatigue, depression and anxiety, according to a real-world study in patients treated with Betaferon (interferon beta-1b).
The study, “Sleep quality, daytime sleepiness, fatigue, and quality of life in patients with multiple sclerosis treated with interferon beta-1b: results from a prospective observational cohort study,” was published in the journal BMC Neurology.
Sleep issues, which can affect quality of life, disease severity, and flare-ups, are common in MS patients. Accordingly, fatigue, which is closely related to sleep disturbances, occurs in nearly 80 percent of MS patients.
Although the precise causes of impaired sleep and increased fatigue have yet to be found, scientists believe that restless legs syndrome — discomfort in the legs and an irresistible urge to move them — may play an important role. The type of MS treatment is also thought to be a key factor, but evidence supporting this link is still lacking. Studies conducted to date have been small and included patients on various treatments, which may introduce variability in medication effects.
Aiming to address these questions, researchers conducted the BETASLEEP study (NCT01766063), sponsored by Bayer. The prospective trial was conducted in Germany and assessed sleep quality, fatigue, quality of life, and coexisting conditions over two years in MS patients taking Betaferon — known as Betaseron in the U.S. and marketed by Bayer — in a real-world setting.
The study enrolled 139 adults with RRMS or CIS from December 2012 to January 2015. CIS is a neurological episode lasting at least 24 hours, characterized by inflammation and loss of myelin (the protective layer of nerve fibers), often preceding the development of MS.
Participants were evaluated at the study’s start, or baseline, and at six, 12, 18, and 24 months. Treatment with Betaferon did not last more than six months.
A total of 128 patients, at a mean age of 41.5 years, of whom 71.1% were women, were available for full analysis; 89.1% had RRMS, and 10.9% had CIS. They had a median Expanded Disability Status Scale (EDSS) score of two, meaning minimal disability in one of the body’s eight functional systems.
Of the patients who quit the study, 35.3% were lost to follow-up, 23.5% withdrew consent to participate, 13.7% switched to another therapy, and 27.5% discontinued for other reasons.
The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality in 106 patients. Of these patients, 62 of 93 RRMS patients and nine of 13 CIS patients were poor sleepers at the study’s start.
The proportion of poor sleepers, indicated by a PSQI score of five or higher, decreased by the end of the study to 37.7% versus 55.47% at the beginning. The team attributed this to the decreasing number of patients with an evaluable sleep score throughout the study, although stable disease course achieved with Betaferon could also be a contributor.
Fatigue — measured by the Modified Fatigue Impact Scale (MFIS) — was higher in poor sleepers than in good sleepers at all study visits. Poor sleepers also showed worse scores on physical and mental components of a health assessment (Short Form-36), depression and anxiety (Hospital anxiety and depression scale), and daytime sleepiness (Epworth Sleepiness Scale) throughout the study.
All six patients diagnosed with restless legs syndrome at the study’s start (four at final visit) were poor sleepers. The proportion of patients with this condition was much lower than in previous research. The team noted that restless legs syndrome may be under-reported, but short disease duration could explain this low prevalence.
Of note, the prevalence of depression (15.4-22.7%) and anxiety (25-34.9%) was lower than in prior studies, a finding possibly explained by lower (better) disability scores, the researchers hypothesized.
The data further showed that poor sleepers had lower MS Functional Composite — measuring leg and hand function, as well as cognition — and a higher, or worse, EDSS disability score at most visits.
PSQI and MFIS scores showed a strong positive correlation, meaning the greater the sleep impairment, the higher the fatigue. A similar strong to moderate link was found with low health status, indicating a lower quality of life.
Links between sleep quality and anxiety, depression, and daytime sleepiness were weaker, but still statistically significant.
Daytime sleepiness and poor sleep quality at the beginning of the study were possible predictors for sleep quality at one year of follow-up. However, there was no variable that predicted sleep quality at the two-year follow-up.
“Taken together, our study confirms the high prevalence of poor sleep quality among patients with MS,” the team wrote. “The results highlight the importance of interventions targeted at improving sleep quality in patients with MS.”
Of note, the lack of a control group prevented an evaluation of the Betaferon effect. However, the medication was used to provide stable treatment conditions, not to analyze its effects on sleep and fatigue, the scientists said.
Six of the seven study authors are former or current employees at Bayer.