Trends in central nervous system-active polypharmacy among people with multiple sclerosis.

BACKGROUND: People with multiple sclerosis (pwMS) are at risk of concurrently using multiple central nervous system (CNS)-active drugs, yet the prevalence of CNS-active polypharmacy remains unmeasured in pwMS. OBJECTIVE: The objective is to measure the prevalence of CNS-active polypharmacy in pwMS. METHODS: This serial, cross-sectional study measured CNS-active polypharmacy in people with MS in the United States from 2008 to 2021 using insurance claims data. CNS-active polypharmacy was defined as the concurrent prescription of ⩾3 CNS-active drugs for >30 continuous days. CNS-active drugs included antidepressants, antiepileptics, antipsychotics, benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants. RESULTS: The number of subjects included at each time point ranged from 23,917 subjects in 2008 to 55,797 subjects in 2021. In 2021, subjects with CNS-active polypharmacy were more likely to be 46-65 years of age and have CNS-related comorbidities compared to those without CNS-active polypharmacy. From 2008 to 2021, the age-adjusted prevalence of CNS-active polypharmacy among female subjects increased from 19.8% (95% confidence interval (CI) = 19.1-20.4) to 26.4% (95% CI = 25.9-26.8) versus 15.9% (95% CI = 14.8-17.0) to 18.6% (95% CI = 17.9-19.2) in male subjects. CONCLUSION: The prevalence of CNS-active polypharmacy has increased among people with MS with a growing disparity by sex.

Outcomes and Health Care Service Use in Adults 50 Years or Older With and Without Multiple Sclerosis: A 6-Year Observational Analysis.

BACKGROUND: Multiple sclerosis (MS) typically presents in young adulthood. Recent data show the highest prevalence of MS in people aged 55 to 64 years; however, there are limited studies of this population. METHODS: Administrative US claims data from IBM-Truven MarketScan commercial and Medicare databases (2011-2017) were analyzed. People with MS 50 years or older were assigned to the aging MS cohort (n = 10,746). The matched controls were people 50 years or older without MS (n = 10,746). Multivariable models compared outcomes between groups. RESULTS: Infections were more frequent in the aging MS cohort vs matched controls (61% vs 45%; P < .0001); urinary tract, acute upper respiratory tract, and herpes zoster were the most frequent infection types. Malignancy rates were 20% for both groups (P = .8167); skin, breast, and prostate malignancies were the most frequent types. Skilled nursing facilities (aging MS cohort, 12%; matched controls, 3%; P < .0001) and MRI (aging MS cohort, 87%; matched controls, 37%; P < .0001) were used more frequently in the aging MS cohort; brain and spine were the most frequent types of MRI in the aging MS cohort. Time to first cane/walker or wheelchair use was shorter in the aging MS cohort (cane/walker use: HR, 2.1; 95% CI, 1.9-2.3; P < .0001; wheelchair use: HR, 6.9; 95% CI, 6.0-8.1; P < .0001). CONCLUSIONS: In people 50 years or older, measures typically associated with worse health primarily resulted from having MS rather than being a consequence of aging alone.

Exploring the relationship between Endothelin-1 and peripheral inflammation in multiple sclerosis.

BACKGROUND: Identifying pathways linking neuroinflammation and neurodegeneration is essential to help prevent disability progression in people with multiple sclerosis (MS). Endothelin-1 (ET-1) is a potent vasoconstrictor thought to contribute to cerebral hypoperfusion and tissue damage in MS. Its link with the neuroinflammatory process remains poorly investigated. OBJECTIVES: To determine plasma ET-1 levels in treatment-naïve people with MS and controls, and the relationship between ET-1 and other peripheral immune mediator levels as potential markers of the disease process. METHODS: This is a retrospective study that included specimens previously collected from 35 treatment-naïve patients with clinically isolated syndrome highly suggestive of MS or definite MS and 35 sex- and age-matched controls. ET-1 plasma levels were measured by enzyme-linked immunosorbent assay (ELISA), and plasma cytokine levels [interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12(p70), IL-13, interferon (IFN)-γ and tumor necrosis factor (TNF)-α] were simultaneously measured by Multiplex assay. RESULTS: ET-1 levels were significantly increased in MS patients compared to controls. No significant difference in cytokine levels between the groups were found. However, a significant increase in IFN-γ/IL-4 ratio was observed in patients with MS in comparison with controls, suggestive of Th1 skewed response. Binary logistic regression was performed to ascertain the effects of age, sex, ET-1 and cytokine levels on the likelihood of MS diagnosis. In the final model, ET-1, IL-4 and IFN-γ levels remained as predictors of MS. There was no significant correlation between ET-1 and cytokine levels. CONCLUSIONS: Patients with MS presented increased levels of ET-1 and an immune response biased towards a Th1 profile. Although both ET-1 and Th1 cytokine profile were predictors of MS diagnosis, ET-1 levels were not associated with peripheral immune markers, suggesting that these changes may occur independently.