Reasons for Healthcare Use Before Onset of Multiple Sclerosis: A Nationwide Matched Cohort Study in Sweden

Abstract

Background: Evidence suggests signs and symptoms may emerge years before the clinical onset of multiple sclerosis (MS). We investigated secondary healthcare use and medication dispensations before MS onset.

Methods: Using linked administrative data, we analyzed a neurologist-diagnosed MS clinical cohort and an algorithm-defined administrative cohort in Sweden (2001-2019). People with MS (PwMS) were matched to up to five non-MS comparators by sex, birth year, residency location, and residency duration before the index date (clinical: symptom onset; administrative: first MS/demyelinating diagnosis code). Annual outpatient visits and hospitalizations by diagnosis codes across 19 years pre-index, and dispensed medications by anatomical and therapeutic classifications across 14 years pre-index were compared.

Results: The clinical cohort included 7604 PwMS and 37,974 matched comparators (median age at symptom onset = 35.5; 68.5% females). In the 5 years pre-index, outpatient visits were 11%-73% higher among PwMS for disturbances of sense organs, nervous, musculoskeletal, digestive, and genitourinary systems, mental health/behavior, and ill-defined symptoms/signs, with visits related to sense organs elevated up to 6 years. Hospitalizations were often elevated in the year pre-index. Dispensations of nervous system-related, musculoskeletal, blood-related, metabolic, sensory, respiratory, and dermatological agents were elevated by 6%-22% in the 5 years pre-index, with elevations in nervous system-related and musculoskeletal agents extending up to 6-9 years pre-index. Findings were similar in the administrative cohort with greater magnitudes and longer durations pre-index.

Conclusions: We observed increased hospital, outpatient, and prescription utilization for multiple body systems 6-9 years pre-MS onset. These patterns provide a more comprehensive picture of the MS prodrome.

Keywords: early signs; hospitalizations; medication use; multiple sclerosis; outpatient visits; prodrome; secondary healthcare use.