Sex and age differences in the Multiple Sclerosis prodrome

Abstract

Background and objectives: Little is known of the potential sex and age differences in the MS prodrome. We investigated sex and age differences in healthcare utilization during the MS prodrome.

Methods: This was a population-based matched cohort study linking administrative and clinical data from British Columbia, Canada (population = 5 million). MS cases in the 5 years preceding a first demyelinating event ("administrative cohort;" n = 6,863) or MS symptom onset ("clinical cohort;" n = 966) were compared to age-, sex- and geographically-matched controls (n = 31,865/4,534). Negative binomial and modified Poisson models were used to compare the rates of physician visits and hospitalizations per international classification of diseases chapter, and prescriptions filled per drug class, between MS cases and controls across sex and age-groups (< 30, 30-49, ≥50 years).

Results: In the administrative cohort, males with MS had a higher relative rate for genitourinary-related visits (males: adjusted Rate Ratio (aRR) = 1.65, females: aRR = 1.19, likelihood ratio test P = 0.02) and antivertigo prescriptions (males: aRR = 4.72, females: aRR = 3.01 P < 0.01). Injury and infection-related hospitalizations were relatively more frequent for ≥50-year-olds (injuries < 30/30-49/≥50: aRR = 1.16/1.39/2.12, P < 0.01; infections 30-49/≥50: aRR = 1.43/2.72, P = 0.03), while sensory-related visits and cardiovascular prescriptions were relatively more common in younger persons (sensory 30-49/≥50: aRR = 1.67/1.45, P = 0.03; cardiovascular < 30/30-49/≥50: aRR = 1.56/1.39/1.18, P < 0.01). General practitioner visits were relatively more frequent in males (males: aRR = 1.63, females: aRR = 1.40, P < 0.01) and ≥50-year-olds (< 30/≥50: aRR = 1.32/1.55, P = 0.02), while differences in ophthalmologist visits were disproportionally larger among younger persons, < 50-years-old (< 30/30-49/≥50: aRR = 2.25/2.20/1.55, P < 0.01). None of the sex and age-related differences in the smaller clinical cohort reached significance (P ≥ 0.05).

Discussion: Sex and age-specific differences in healthcare use were observed in the 5 years before MS onset. Findings demonstrate fundamental heterogeneity in the MS prodromal presentation.

Keywords: Multiple Sclerosis; age; healthcare use; prodromal; sex.

Figure 1

Multiple sclerosis (MS) cases vs. controls in the 5 years before the first demyelinating diagnostic code: sex-specific rate ratios for (A) physician visits and (B) hospitalizations per International Classification of Diseases-9/10 chapter, (C) physician visits per specialty, and (D) prescriptions-filled per Anatomical Therapeutic Chemical (ATC) level 1 classification. Results were not reported if a model failed to converge due to low counts or the 95% CIs were wide (exceeded 100). *P < 0.05, **P < 0.01, *** P < 0.001 indicates that the rate ratios were statistically different between men and women, based likelihood ratio tests. ^‡Amantadine was categorized as a nervous system drug, based on the Anatomical Therapeutic Chemical (ATC) level I classification system.

Figure 2

Multiple Sclerosis (MS) cases vs. controls in the 5 years before the first demyelinating diagnostic code: age-specific rate ratios for (A) physician visits and (B) hospitalizations per International Classification of Diseases-9/10 chapter, (C) physician visits per specialty, and (D) prescriptions-filled per Anatomical Therapeutic Chemical (ATC) level 1 classification. Results were not reported if a model failed to converge due to low counts or the 95% CIs were wide (exceeded 100). *P < 0.05, **P < 0.01, *** P < 0.001 indicates that the rate ratios are statistically different across age groups, based on Bonferroni tests following likelihood ratio tests. ^‡Amanradine was categorized as a nervous system drug, based on the Anatomical Therapeutic Chemical (ATC) level 1 classification system.

Figure 3

Infographic summarizing the sex and age differences in health-care use in the 5 years preceding a first demyelinating event, grouped by the main condition or body system affected^†‡. The infographic depicts all the significant findings for the hospitalizations, physician visits, prescriptions filled and the comorbidities examined. For example, the relative rates of GP visits (shaded in blue), was greater in men with MS in the 5 years preceding a 1st demyelinating event than women with MS. ^†Comorbidities are conditions identified in the 5-years preceding a 1st demyelinating event via validated health administrative algorithms. ^‡Disease and drug classes, specialty visits and comorbidities were compared between MS cases and controls across sex and age groups in the 5 years preceding a 1st demyelinating event. Those that showed significant sex-based differences via likelihood ratio tests or age-based differences via Bonferroni-adjusted tests are displayed.