Multiple sclerosis in a multi-ethnic population from Northern California: a retrospective analysis, 2010-2016.

BACKGROUND: Research is needed to examine differences in multiple sclerosis (MS) prevalence by race-ethnicity. The goal of this study was to quantify MS prevalence in a health care system in Northern California and examine differences in prevalence and phenotype by race-ethnicity. METHODS: We conducted a retrospective, observational cohort study of adults (2010-2016). MS prevalence estimates were standardised to distributions of gender and race-ethnicity for the underlying geographic region and stratified by gender and race-ethnicity with age adjustment. We performed a chart review of a racial-ethnic stratified sample of patients to examine disease phenotypes. RESULTS: 1,058,102 patients were identified, of which 3286 had MS. The overall direct-standardised prevalence was 288.0 cases per 100,000 population (95% confidence interval: 276.3-299.8). Age-adjusted prevalence ranged from 677.0 per 100,000 among non-Hispanic black women to 49.7 per 100,000 among non-Hispanic Asian men. Non-Hispanic blacks compared with other groups more often had primary-progressive (10.0% vs. 0.0-4.0%) or progressive-relapsing MS (6.0% vs. 0.0-2.0%). CONCLUSIONS: In this Northern Californian Cohort, between 2010 and 2016 the direct-standardised MS prevalence was estimated at 288.0 per 100,000 population, and increased over time. Non-Hispanic blacks, especially women, were disproportionately affected and had less common, earlier progressive MS phenotypes.

Identification of short-term pharmacodynamic effects of interferon-beta-1a in multiple sclerosis subjects with broad- based phenotypic profiling.

We applied broad-based phenotypic profiling to identify pharmacodynamic markers for interferon-beta in multiple sclerosis subjects. A strong pharmacodynamic effect was observed 1.5 (short-term) vs. 6 days post weekly injection. Hundreds of differences were observed at a p-value <0.001. Most major cell populations, including neutrophils, B cells, CD4 T cells and CD8 T cells, decreased in absolute counts at 1.5 days. The striking exception was monocytes, which increased substantially. Changes in multiple monocyte-associated cell surface molecules and monocyte related soluble factors were also observed, including: HLA class II, CCR5, CD38, CD40, CD54, CD64, CD69, CD86, CD101, TLR2, TLR4 and MCP2. These results demonstrate that new hypotheses can be generated from broad molecular and cellular profiling in a clinical setting and provide an approach to identify candidate pharmacodynamic markers to evaluate new drug formulations, dosing and bioequivalence.