Clinical Characteristics and Long-Term Outcomes of Late-Onset Multiple Sclerosis: A Swedish Nationwide Study

Abstract

Background and objectives: Clinical onset of multiple sclerosis (MS) after the age of 50 years is uncommon and associated with a less favorable natural history. The differences in long-term outcomes in patients with late-onset MS (LOMS, onset 50 years or older) and adult-onset MS (AOMS, onset 18 years or older and younger than 50 years) during the disease-modifying therapy (DMT) era have been less studied. This study aimed to compare patient characteristics, DMT exposure, and disability progression in Swedish patients with LOMS and AOMS over 2 decades (2001-2022).

Methods: The nationwide Swedish MS registry was searched for patients with an onset of MS between January 1, 2001, and December 31, 2018, with symptom onset at age 18 years or older and ≥2 recorded Expanded Disability Status Scale (EDSS) scores. Clinical and demographic parameters and exposure to DMT were compared between LOMS and AOMS. Time to disability milestones (EDSS 4 and 6) was assessed using Kaplan-Meier curves and Cox proportional hazards regression models adjusted for sex, disease course, calendar year at onset, and DMT exposure.

Results: Among 8739 patients with MS who met inclusion criteria, 1,028 (11.8%) were LOMS. Primary progressive MS was more frequently diagnosed in LOMS compared with that in AOMS (25.2% vs 4.5%; p < 0.001). Most of the patients had been prescribed DMT, but more rarely in LOMS compared with AOMS (74.7% vs 95.6%; p < 0.001). Less than half of patients with LOMS had been exposed to a high-efficacy DMT (45.8%) compared with 73.5% of AOMS (p < 0.001). The risk of reaching disability milestones was greater for LOMS compared with that for AOMS (EDSS 4; adjusted hazard ratio [aHR] 2.71; 95% CI 2.22-3.30; p < 0.001, and EDSS 6; aHR 2.67; 95% CI 2.12-3.36; p < 0.001).

Discussion: This study distinguishes LOMS as a particularly vulnerable group and clinically supports close vigilance of these patients. Further studies are needed to assess and clarify the benefit of DMT usage in older adults with MS.

Figure 1. Flowchart of Patient Inclusion

EDSS = Expanded Disability Status Scale; MS = multiple sclerosis.

Figure 2. Treatment Exposure in the Study Population

(A) Late-onset multiple sclerosis (LOMS); (B) Adult-onset multiple sclerosis. PPMS = primary progressive multiple sclerosis; RRMS = relapsing-remitting multiple sclerosis. Modest (efficacy) DMT: interferon beta-1a, interferon beta-1b, pegylated interferon beta-1a, glatiramer acetate, dimethyl fumarate, and teriflunomide. High (efficacy) DMT: rituximab, ocrelizumab, natalizumab, alemtuzumab, fingolimod, cladribine, daclizumab, and autologous hematopoietic stem cell transplantation.

Figure 3. Kaplan-Meier Curves of Time to Confirmed Sustained EDSS 4 and 6

Total cohort (A), RRMS subcohort (B), PPMS subcohort (C). AOMS = adult-onset multiple sclerosis; LOMS = late-onset multiple sclerosis; PPMS = primary progressive multiple sclerosis; RRMS = relapsing-remitting multiple sclerosis.