Decreasing impact of late relapses on disability worsening in secondary progressive multiple sclerosis.

Background: Changes in relapse activity during secondary progressive multiple sclerosis (SPMS) need to be accurately characterized in order to identify patients who might benefit from continuing disease-modifying therapies. Objective: To describe relapse occurrence in patients with SPMS during long-term follow-up and assess its impact on disability worsening. Methods: This retrospective cohort study included 506 patients. We assessed the influence of relapses on time from SPMS onset to an Expanded Disability Status Scale score of 6 (EDSS 6), and on irreversible worsening of EDSS scores across different periods. Results: The annualized relapse rate (ARR) decreased with patient's age (mean reduction of 43% per decade) and SPMS duration (mean reduction of 46% every 5 years). Post-progression relapses were associated with shorter time from secondary progressive (SP) phase onset to EDSS 6 (hazard ratio (HR) = 1.29, 95% confidence interval (CI) = (1.01, 1.64)). Relapse occurrence during the first 3 years and 3-5 years after SP onset was associated with an increased risk of irreversible EDSS worsening (OR = 3.12 (1.54, 6.31) and 2.04 (1.16, 3.58)). This association was no longer significant after 5 years. Conclusion: The occurrence of relapses was a marker of short-term disability progression during early SPMS, but did not have decisive impact in later SPMS.