The canadian prospective cohort (CANPROCO) study to understand progression in multiple sclerosis: rationale and baseline characteristics

Background: Neurological disability progression occurs across the spectrum of people living with multiple sclerosis (PwMS) Currently, no treatments exist that substantially modify the course of clinical progression in MS, one of the greatest unmet needs in clinical practice Characterizing the determinants of clinical progression is essential for the development of novel therapeutic agents and treatment approaches that target progression in PwMS Objectives: The overarching aim of CanProCo is to evaluate a wide spectrum of factors associated with the onset and rate of disease progression in MS, and to describe how these factors interact with one another to influence progression Methods: CanProCo is a prospective, observational cohort study aiming to recruit 1000 individuals with radiologically-isolated syndrome (RIS), relapsing-remitting MS (RRMS), and primary-progressive MS (PPMS) within 10-15 years of disease onset, and 50 healthy controls (HCs) from five large academic MS centers in Canada Participants undergo detailed clinical evaluations annually A subset of participants enrolled within 5-10 years of disease onset (n=500) also have blood, cerebrospinal fluid, and MRIs collected facilitating study of biological measures (e g single-cell RNAsequencing[ scRNASeq]), MRI-based microstructural assessment, participant characteristics (self-reported, performance-based, clinician- assessed, health-system based), and environmental factors as determinants contributing to the differential progression in MS Results: Recruitment commenced in April/May 2019 and n=536 patients have been recruited to date (RRMS=457, PPMS=35, RIS=25, HC=19) Baseline age, sex distribution, and Expanded Disability Status Scale (EDSS) scores (median, range) of each subgroup are: RRMS=38 years, 73% female, EDSS=1 5 (0-6 0);PPMS=52 years, 40% female, EDSS=4 0 (1 5-6 5);RIS=41 years, 68% female, EDSS=0 (0-3 0);HC=37 years, 63% female Recruitment has surpassed the 50% target but has been paused due to the COVID-19 pandemic scRNASeq on frozen blood samples has been validated Conclusions: Halting the progression of MS is a fundamental clinical need to improve the lives of PwMS Achieving this requires leveraging transdisciplinary approaches to better characterize mechanisms underlying clinical progression CanProCo is the first prospective cohort study aiming to characterize these determinants to inform the development and implementation of efficacious and effective interventions