Moderate–high efficacy disease-modifying therapies reduce relapse risk in late-onset multiple sclerosis

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INTRODUCTION: Late-onset multiple sclerosis (LOMS) now comprises over 10% of MS diagnoses in contemporary cohorts. The effectiveness of disease-modifying therapies (DMTs) in LOMS is unclear. We aimed to establish the comparative effectiveness of moderate-high-efficacy versus low-efficacy DMTs in LOMS. METHODS: Using data from the MSBase registry, this multicentre cohort study included people with MS with symptom onset after age 50. Covariates were balanced using inverse-probability-treatment-weighting (IPTW). Primary outcomes were time to first relapse and annualised relapse rate (ARR). Secondary outcomes were 6-month confirmed disability progression (CDP), confirmed disability improvement (CDI), relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA). RESULTS: Of 1032 participants, 472 received moderate-high-efficacy DMTs and 560 received low-efficacy DMTs. IPTW-weighted ARR was 0.06 for moderate-high-efficacy and 0.09 for low-efficacy DMTs, corresponding to an ARR ratio of 0.68 (95% CI 0.50 to 0.93, p=0.01). HR for time to first relapse was 0.66 (95% CI 0.47 to 0.91, p=0.01) in favour of moderate-high-efficacy DMTs.Among 856 participants with adequate follow-up, 37% experienced CDP over a median of 4.43 years, with most events (83.6%) attributable to PIRA. The HR for time to CDP was 0.78 (p=0.08) and RAW was 0.69 (p=0.31) in favour of moderate-high-efficacy DMTs, though neither reached statistical significance. There was no difference in CDI or PIRA. CONCLUSION: Moderate-high-efficacy DMTs reduced relapse risk in LOMS. Relapse activity was low. CDP was common and driven by PIRA. Although the CDP and RAW results did not reach statistical significance, the overall findings support the initial use of moderate-high-efficacy DMTs in LOMS.

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