Family history of multiple sclerosis and long-term outcomes

Abstract

Family history is a well-established risk factor for multiple sclerosis (MS), but its influence on disease progression remains unclear. We investigated whether familial MS, including degree of relatedness, is associated with baseline characteristics and disease outcomes. We included individuals with incident MS from the Swedish population-based epidemiologic investigation of multiple sclerosis study with longitudinal follow-up through the Swedish MS registry. Participants were categorized as having no family history of MS, first-degree familial MS, or second-/third-degree familial MS. Outcomes included confirmed disability worsening (CDW), progression to Expanded Disability Status Scale milestones 3 and 4, cognitive worsening measured by the symbol digit modalities test, MRI disease activity, and worsening on the Multiple Sclerosis Impact Scale-29. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox regression. Among 3,094 participants, 239 (7.7%) reported a first-degree relative with MS and 468 (15.1%) reported a second-/third-degree relative with MS. Baseline characteristics were similar across groups, although HLA–DRB1*15:01 positivity was more common among individuals with first-degree familial MS. No significant associations were observed between familial MS status and disability progression, cognitive decline, MRI disease activity, or patient-reported worsening. Compared with individuals without a known family history of MS, the HR for CDW was 1.06 (95% CI 0.89–1.30) among individuals with first-degree familial MS and 1.04 (95% CI 0.90–1.20) among those with second-/third-degree familial MS. Family history of MS did not appear to have a substantial prognostic impact on long-term disease outcomes after MS onset.