Abstract
BackgroundNeurological disability progression occurs across the spectrum of people living with multiple sclerosis (MS). Although there are a handful of disease-modifying treatments approved for use in progressive phenotypes of MS, there are no treatments that substantially modify the course of clinical progression in MS. Characterizing the determinants of clinical progression can inform the development of novel therapeutic agents and treatment approaches that target progression in MS, which is one of the greatest unmet needs in clinical practice. Canada, having one of the world’s highest rates of MS and a publicly-funded health care system, represents an optimal country to achieve in-depth analysis of progression. Accordingly, the overarching aim of the Canadian Prospective Cohort Study to Understand Progression in MS (CanProCo) is to evaluate a wide spectrum of factors associated with the clinical onset and rate of disease progression in MS, and to describe how these factors relate to one another to influence progression.MethodsCanProCo is a prospective, observational cohort study with investigators specializing in epidemiology, neuroimaging, neuroimmunology, health services research and health economics. CanProCo’s study design was approved by an international review panel, comprised of content experts and key stakeholders. One thousand individuals with radiologically-isolated syndrome, relapsing-remitting MS, and primary-progressive MS within 10–15 years of disease onset will be recruited from 5 academic MS centres in Canada. Participants will undergo detailed clinical evaluation annually over 5 years (including advanced, app-based clinical data collection). In a subset of participants within 5–10 years of disease onset (n = 500), blood, cerebrospinal fluid, and research MRIs will be collected allowing an integrated, in-depth evaluation of factors contributing to progression in MS from multiple perspectives. Factors of interest range from biological measures (e.g. single-cell RNA-sequencing), MRI-based microstructural assessment, participant characteristics (self-reported, performance-based, clinician-assessed, health-system based), and micro and macro-environmental factors.DiscussionHalting the progression of MS remains a fundamental need to improve the lives of people living with MS. Achieving this requires leveraging transdisciplinary approaches to better characterize why clinical progression occurs. CanProCo is a pioneering multi-dimensional cohort study aiming to characterize these determinants to inform the development and implementation of efficacious and effective interventions.
Highlights
Neurological disability progression occurs across the spectrum of people living with multiple sclerosis (MS)
(as defined by Expanded Disability Status Scale (EDSS) according to typical clinical trial criteria or brain atrophy rate).Summary: Odds ratio is 0.59–0.64 for a continuous variable, 0.3–0.36 for a binary variable, which is reasonable for most imaging and biological measures
Summary: Odds ratio is 0.49– 0.54 for a continuous variable, 0.17–0.23 for a binary variable, which is reasonable for most imaging and biological measures
Summary
Neurological disability progression occurs across the spectrum of people living with multiple sclerosis (MS). There has been considerable progress in the field of MS, including the development of many treatment options for the relapsing-remitting (RRMS) phenotype of the disease. MS has been divided into specific phenotypes, including relapsing remitting and progressive forms. Accumulating evidence suggests that despite the designation of MS into phenotypes of relapsing or progressive form, MS likely exists on a disease continuum and biological and clinical disease progression is a component of the disease from the onset [2]. A variety of clinical, biological, genetic, environmental, and health systems factors interact in complex ways to affect MS disease onset and clinical manifestations, which include relapses and disability progression over time. A thorough understanding of biological mechanisms and the complex interplay of various factors related to disease progression is a necessary stepping-stone to develop more targeted and effective disease-modifying treatments and treatment strategies for progression in MS
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