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Background: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a poorly understood and heterogeneous manifestation of SLE. Common major NPSLE syndromes include strokes, seizures, myelitis, and aseptic meningitis. Easily obtainable biomarkers are needed to assist in early diagnosis and improve outcomes for NPSLE. A frequent end-result of major syndromes is neuronal or glial injury. Blood-based neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) have been utilized as markers for monitoring disease activity and/or severity in other neurodegenerative and neuroinflammatory diseases; however, they have not been evaluated in active major NPSLE. Methods: This was a case-control study. We enrolled patients aged 12-60 years with active major NPSLE, SLE without active major NPSLE, and healthy controls. Active NPSLE was defined as being <6 months from last new or worsening neuropsychiatric symptom. Demographics, clinical data, and serum or plasma biosamples were collected. Results: Thirteen patients with active major NPSLE, 13 age/sex/kidney function matched SLE controls without active major NPSLE, and 13 age/sex matched healthy controls (mean ages 26.8, 27.3, 26.6 years) were included. 92% of each group were female. Major syndromes included stroke (5), autonomic disorder (3), demyelinating disease (2), aseptic meningitis (2), sensorimotor polyneuropathy (2), cranial neuropathy (1), seizures (1), and myelopathy (2). Mean (standard deviation) blood NfL and GFAP were 3.6 pg/ml (2.0) and 50.4 pg/ml (15.0), respectively, for the healthy controls. Compared to healthy controls, SLE without active major NPSLE had mean blood NfL and GFAP levels 1.3 pg/ml (p =.42) and 1.2 pg/ml higher (p =.53), respectively. Blood NfL was on average 17.9 pg/ml higher (95% CI: 9.2, 34.5; p <.001) and blood GFAP was on average 3.2 pg/ml higher (95% CI: 1.9, 5.5; p <.001) for cases of active major NPSLE compared to SLE without active major NPSLE. In a subset of 6 patients sampled at multiple time points, blood NfL and GFAP decreased after immunotherapy. Conclusions: Blood NfL and GFAP levels are elevated in persons with SLE with active major NPSLE compared to disease matched controls and may lower after immunotherapy initiation. Larger and longitudinal studies are needed to ascertain their utility in a clinical setting. [ABSTRACT FROM AUTHOR]

Objective: Our objectives were to (1) obtain the prevalence and demography of people with multiple sclerosis (MS) in a representative Colorado population, and (2) to assess the utilization of disease‐modifying therapy within this prevalent cohort. Methods: This is a retrospective, observational study of patients that had contact with the University of Colorado Health System from 2012 to 2020. We queried Health Data Compass, a data warehouse, for patient data and applied the MS Prevalence Workgroup Algorithm to generate a prevalent cohort. We calculated prevalence as of 31 December 2020, and stratified by age, sex, race, and ethnicity. Payer information and treatment exposure were obtained from linked claims from the Colorado All Payers Claim Database. Disease‐modifying therapies were classified as highly effective and moderately effective based on the clinical trial, TREAT‐MS (NCT03500328). Results: From a population of 1,382,821 individuals, 8557 people with MS were captured. Age‐adjusted prevalence of MS as of 31 December 2020 was 572.3 per 100,000 with a mean age of 47.36. Prevalence varied between demographic subgroups, with the lowest prevalence in Hispanic men (215.6) and highest in White (824.1) and Black women (820.1). Overall disease‐modifying therapy exposure was 62.4%, with increased highly effective therapy use and a corresponding decrease in moderately effective therapy use on a yearly basis. Interpretation: MS is highly prevalent in a representative Colorado cohort. Overall treatment and proportion of highly effective therapy exposure increased significantly during a critical period of MS therapeutic advances, indicating a shift in disease management driven sharply by the availability of on‐label anti‐CD20 therapy. [ABSTRACT FROM AUTHOR]

The United States has begun assessing the value of pharmaceuticals to inform negotiated prices in the Medicare program. Given strong political objections in the United States to the use of QALYs, Medicare will need to adopt an alternative approach to measuring value. In this narrative review, we identified six alternative approaches to measuring value (equal value life-years, health years in total, generalized risk-adjusted cost-effectiveness, severity weighting based on absolute or proportional shortfall, comparative effectiveness based on conventional clinical endpoints, and comparative effectiveness based on both conventional endpoints and patient-centric value elements) and five criteria for assessing these approaches (responsiveness to concerns about discrimination, feasibility, transparency, flexibility, and the ability to incorporate factors beyond traditional value elements). Four of the alternatives are broadly aligned with the cost-effectiveness framework, but none fully addresses all aspects of the stated concerns that QALYs may be used to unintentionally implement discrimination. We note, however, that the extent to which these concerns lead to discrimination in practice is unknown. Finally, we recommend an approach for measuring value in terms of comparative effectiveness that combines quantitative ranking and weighting of distinct criteria (including patient-centric value elements) with deliberation. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic, immune-mediated, neurodegenerative condition that results in progressive accumulation of disability over the course of the disease. MS presents heterogeneously, and, as the disease progresses, patients develop a range of physical and neurologic problems that include reduced mobility, cognitive impairment, weakness, fatigue, pain, and defects in speech or vision. Economically, MS is costly, including both direct costs stemming from clinical care and medications and the indirect costs of productivity losses. These costs pose a substantial burden to patients, families, caregivers, employers, and society. There are 21 approved disease-modifying therapies for MS across several drug classes. The importance of early MS treatment has been confirmed, and progress has been made in the treatment of relapsing-remitting MS, although this progress has not been replicated for progressive presentations of the disease. Ongoing research continues to elucidate the exact mechanisms of disease in MS as well as potential new treatment strategies that may better address current gaps, such as disability progression in secondary progressive MS without activity. One of the novel pathways under investigation is the inhibition of Bruton tyrosine kinase, a cytoplasmic tyrosine kinase, which is expressed in B cells and other potentially targetable hematopoietic lineage cells. This review examines emerging hypotheses that targeting both B cells and myeloid cells within the periphery and central nervous system could yield clinical effects in key areas of MS pathophysiology that are currently unaddressed. [ABSTRACT FROM AUTHOR]