M Mateo Paz Soldán1, Martina Novotna1, Nuhad Abou Zeid1, Nilufer Kale1, Melih Tutuncu1, Daniel J Crusan1, Elizabeth J Atkinson1, Aksel Siva1, B Mark Keegan1, Istvan Pirko1, Sean J Pittock1, Claudia F Lucchinetti1, Brian G Weinshenker1, Moses Rodriguez1, Orhun H Kantarci2. 1. From the Mayo Clinic Center for Multiple Sclerosis and CNS Demyelinating Diseases, Department of Neurology (M.M.P.S., M.N., B.M.K., I.P., S.J.P., C.F.L., B.G.W., M.R., O.H.K.), and Division of Biomedical Statistics & Informatics (D.J.C., E.J.A.), Mayo Clinic College of Medicine, Rochester, MN; International Clinical Research Center (M.N.), St. Anne's University Hospital Brno, Czech Republic; Department of Neurology (N.A.Z.), American University of Beirut Medical Center, Lebanon; Department of Neurology (N.K.), Bakirkoy State Hospital, Istanbul; and Department of Neurology (M.T., A.S.), Cerrahpasa School of Medicine, Istanbul University, Turkey. N.A.Z., N.K., and M.T. were previous fellows of the Department of Neurology, Mayo Clinic College of Medicine. 2. From the Mayo Clinic Center for Multiple Sclerosis and CNS Demyelinating Diseases, Department of Neurology (M.M.P.S., M.N., B.M.K., I.P., S.J.P., C.F.L., B.G.W., M.R., O.H.K.), and Division of Biomedical Statistics & Informatics (D.J.C., E.J.A.), Mayo Clinic College of Medicine, Rochester, MN; International Clinical Research Center (M.N.), St. Anne's University Hospital Brno, Czech Republic; Department of Neurology (N.A.Z.), American University of Beirut Medical Center, Lebanon; Department of Neurology (N.K.), Bakirkoy State Hospital, Istanbul; and Department of Neurology (M.T., A.S.), Cerrahpasa School of Medicine, Istanbul University, Turkey. N.A.Z., N.K., and M.T. were previous fellows of the Department of Neurology, Mayo Clinic College of Medicine. kantarci.orhun@mayo.edu.
Abstract
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.
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.
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