To determine if age at multiple sclerosis (MS) onset is associated with outcomes at age 50.

Older age at MS onset is associated with worse 10-year outcomes, potentially influencing choice of high-efficacy disease-modifying therapies (DMT) in older, compared with younger, patients. However, data on outcomes beyond 10 years is limited and age-related comorbidities may also contribute to disability. Therefore, we investigated outcomes at age 50—when patients may still be active, working, and have similar age-related comorbidities.

Patients with greater than 10 years disease-duration, and with clinical and MRI outcomes measured at age 50, were included. Age at MS onset, sex, time to DMT initiation, number of DMTs, exposure to high-efficacy DMT, and date of 50-year visit were collected. Outcomes at age 50 included Expanded Disability Status Score (EDSS), secondary-progressive MS (SPMS), brain T2-lesion volume (T2LV), and brain parenchymal fraction (BPF). Multiple regression was used to determine how age at onset is associated with outcomes at age 50 when adjusting for other factors.

550 patients were included with mean (SD) MS onset at age 30.8 (6.6). First-line injectable DMTs were started in 478 (86.9%), 212 (38.5%) transitioned to high-efficacy DMT by age 50, and 188 (34.2%) developed SPMS. At age 50, for every 5 years earlier that first symptoms developed, the average EDSS was 0.42 points worse (95%CI: 0.29-0.55, p<0.001), odds of developing SPMS were 1.56 times higher (95%CI: 1.35-1.79, p<0.001), T2LV was 1.16cm³ greater (95%CI: 0.60-1.70, p<0.001), and BPF was 0.55% lower (95%CI: 0.30-0.80, p<0.001). Adjusting for other factors, younger age at onset remained significantly associated with worse prognosis for all outcomes.

All outcomes at age 50 were worse in patients who developed first MS symptoms at a younger age, not older. Treatment of younger patients with high-efficacy DMT earlier may reduce disability at age 50 and requires further study.