Health-care use before a first demyelinating event suggestive of a multiple sclerosis prodrome: a matched cohort study

Background Degenerative processes in neurodegenerative diseases can start years before clinical manifestation. We aimed to establish whether a multiple sclerosis prodromal period exists by examining patterns of health-care use before a first demyelinating event. Methods In this matched cohort study, we used data from linked health administrative and clinical databases from four Canadian provinces (British Columbia, Saskatchewan, Manitoba, and Nova Scotia) to compare hospital, physician, and prescription use data from people with multiple sclerosis and matched general population controls in the 5 years before the first demyelinating disease claim (health administrative index date) or clinically reported symptom onset (clinical index date). Rate ratios (RRs) were estimated using negative binomial regression and combined across provinces using random effect models. The primary outcome was all-cause use of health care during each of the 5 years before the health administrative or clinical index date. Findings The health administrative cohort included 14 428 multiple sclerosis cases and 72 059 matched controls for whom data were available between April, 1984, and April, 2014. Annual health-care use increased steadily between 5 years and 1 year before the first demyelinating disease claim in people with multiple sclerosis compared with controls (from RR 1.26 [95% CI 1.16-1.36] to 1.78 [1.50-2.10] for hospital admissions; from 1.24 [1.16-1.32] to 1.88 [1.72-2.07] for physician claims; and from 1.23 [1.06-1.41] to 1.49 [1.41-1.59] for prescriptions, assessed as drug classes). Similar patterns for physician claims and prescriptions were observed in the cohort with available clinical symptom onset (3202 individuals with multiple sclerosis and 16 006 controls), although the differences in use in each of the 5 years mostly did not reach statistical significance. Interpretation More frequent use of health care in patients with multiple sclerosis than in controls in the 5 years before a first demyelinating event, according to health administrative data, suggests the existence of a measurable multiple sclerosis prodrome. These findings have clinical and research implications, including the establishment of an earlier window of opportunity to identify and potentially treat multiple sclerosis.