Age-Related Disability Outcomes After a First Demyelinating Event

BACKGROUND AND OBJECTIVES: Emerging concepts in the early detection of multiple sclerosis (MS) progression reveal that disability accumulation can start early in the disease course. Aging in MS is increasingly recognized as a key factor for disease progression and disability accrual. We evaluate the prognostic impact of age in a cohort of patients experiencing a first demyelinating event (FDE), using a variety of disability outcomes, including some not previously assessed in age-specific studies.

METHODS: Patients aged 18-50 years, assessed within 3 months from the FDE, were prospectively included since 1994 and categorized into 3 age groups: 18-29, 30-39, and 40-50 years. Relapse-associated worsening (RAW) at FDE, annualized relapse rate, and EDSS trajectories during follow-up were compared across age groups. Cox regression analyses adjusted for sex, comorbidities, and time exposed to very high-efficacy drugs were performed to assess the risk of achieving the following outcomes: time to reach McDonald 2017 criteria, first relapse, recurrent RAW, >2 new T2 brain lesions/year, first progression independent of relapse activity (PIRA), confirmed disability accumulation (CDA), and confirmed EDSS score 3.0. Patient-reported outcome measures were also analyzed.

RESULTS: A total of 1,170 patients were included (median age 32 years; 69% female). The 40-50 group had a higher proportion of RAW at FDE (34% vs 25% and 29%; p = 0.031) and less time exposed to very high-efficacy treatments ( p < 0.001) than the 30-39 and 18-29 groups, respectively. EDSS trajectories in the 40-50 group displayed a greater annual increase in the EDSS score compared with the 18-29 group (β 0.019 [95% CI 0.0001; 0.0387]). Cox analyses (HR; 95% CI) showed that the 40-50 group was at lower risk to reach McDonald 2017 criteria (0.80; 0.67-0.96), first relapse (0.59; 0.47-0.74), recurrent RAW (0.51; 0.31-0.86), or >2 new T2 brain lesions/year (0.39; 0.30-0.52), but at a higher risk of CDA (1.49; 1.16-1.97), PIRA (2.48; 1.88-3.27), and EDSS score 3.0 (1.50; 1.05-2.12), than the 18-29 group. Different functional and well-being variables were more affected in the 40-50 group, compared with 30-39 and 18-29 groups ( p values< 0.05).

DISCUSSION: Patients with a FDE at 40-50 years exhibit less inflammatory outcomes compared with younger patients and reach outcomes more closely related to neurodegeneration despite the lower disease activity.