Abstract
OBJECTIVE: Phenotype hospital, physician, and emergency department (ED) visits by diagnoses and specialty up to 29 years pre-multiple sclerosis (MS) onset versus a matched population without MS. METHODS: We identified people with MS (PwMS) using population-based administrative data from Ontario, Canada (1991-2020). The first MS/demyelinating diagnostic code defined MS onset (the index date). Annual rates of healthcare use (hospital, physician, ED) by primary diagnosis (chapter-level) and physician specialty pre-index were compared between PwMS and up to 5 matched population comparators using overdispersed-Poisson regression. RESULTS: Up to 35,018 PwMS and 136,007 population comparators were included. Consistently elevated yearly physician visit rate ratios (RRs) were observed 28 years pre-index for: mental-health (RR > 1.29) and ill-defined signs/symptoms (RR > 1.15), 24 years for: nervous (RR > 1.47), musculoskeletal (RR > 1.21), injury, and respiratory-related issues (RR > 1.07), and 22 years for digestive-system (RR > 1.18). The magnitude increased as the index date approached, peaking the year pre-index for physician, hospital, and ED visit RRs for: nervous-system (range: 12.06-17.13); ill-defined signs/symptoms (range: 3.51-5.45), mental-health (range: 2.13-2.70), musculoskeletal (range: 1.84-2.96), injury (range: 1.58-2.27), digestive-system (range: 1.49-1.78) and respiratory-system (range: 1.37-2.06). By specialty, yearly visit RRs for primary care were > 1.08 for 28 years pre-index, internal medicine exceeded 1.19 for 25 years, and psychiatry and neurology > 1.52 for 24 years pre-index. INTERPRETATION: Higher healthcare use was evident for over two decades before the first demyelinating event. Mental-related, ill-defined signs/symptoms and primary care visits were consistently elevated the longest (28 years pre-index), followed by nervous-system, musculoskeletal, injury, respiratory-related, and digestive-system (22-24 years pre-index). Health-related phenotypical differences appear early in the MS disease process.