Objective: We examined the effect of relapses—before and after progression onset—on the rate of postprogression disability accrual in a progressive multiple sclerosis (MS) cohort.
Methods: We studied patients with primary progressive MS (n = 322) and bout-onset progressive MS (BOPMS) including single-attack progressive MS (n = 112) and secondary progressive MS (n = 421). The effect of relapses on time to Expanded Disability Status Scale (EDSS) score of 6 was studied using multivariate Cox regression analysis (sex, age at progression, and immunomodulation modeled as covariates). Kaplan-Meier analysis was performed using EDSS 6 as endpoint.
Results: Preprogression relapses (hazard ratio [HR]: 1.63; 95% confidence interval [CI]: 1.34–1.98), postprogression relapses (HR: 1.37; 95% CI: 1.11–1.70), female sex (HR: 1.19; 95% CI: 1.00–1.43), and progression onset after age 50 years (HR: 1.47; 95% CI: 1.21–1.78) were associated with shorter time to EDSS 6. Postprogression relapses occurred in 29.5% of secondary progressive MS, 10.7% of single-attack progressive MS, and 3.1% of primary progressive MS. Most occurred within 5 years (91.6%) after progressive disease onset and/or before age 55 (95.2%). Immunomodulation after onset of progressive disease course (HR: 0.64; 95% CI: 0.52–0.78) seemingly lengthened time to EDSS 6 (for BOPMS with ongoing relapses) when analyzed as a dichotomous variable, but not as a time-dependent variable.
Conclusions: Pre- and postprogression relapses accelerate time to severe disability in progressive MS. Continuing immunomodulation for 5 years after the onset of progressive disease or until 55 years of age may be reasonable to consider in patients with BOPMS who have ongoing relapses.
Neurology 2014
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