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Relapses and disability accumulation in progressive multiple sclerosis
MM. Paz Soldán, M. Novotna, N. Abou Zeid, N. Kale, M. Tutuncu, DJ. Crusan, EJ. Atkinson, A. Siva, BM. Keegan, I. Pirko, SJ. Pittock, CF. Lucchinetti, BG. Weinshenker, M. Rodriguez, OH. Kantarci,
Language English Country United States
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Persistent link
https://www.medvik.cz/link/bmc15022932
- MeSH
- Multiple Sclerosis, Chronic Progressive drug therapy physiopathology MeSH
- Adult MeSH
- Immunologic Factors therapeutic use MeSH
- Kaplan-Meier Estimate MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Multivariate Analysis MeSH
- Disability Evaluation MeSH
- Disease Progression MeSH
- Proportional Hazards Models MeSH
- Recurrence MeSH
- Severity of Illness Index MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
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.
Department of Neurology American University of Beirut Medical Center Lebanon
Department of Neurology Bakirkoy State Hospital Istanbul
International Clinical Research Center St Anne's University Hospital Brno Czech Republic
References provided by Crossref.org
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- $a Paz Soldán, M Mateo $u 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.
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- $a Relapses and disability accumulation in progressive multiple sclerosis / $c MM. Paz Soldán, M. Novotna, N. Abou Zeid, N. Kale, M. Tutuncu, DJ. Crusan, EJ. Atkinson, A. Siva, BM. Keegan, I. Pirko, SJ. Pittock, CF. Lucchinetti, BG. Weinshenker, M. Rodriguez, OH. Kantarci,
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- $a 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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- $a Novotna, Martina $u 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.
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- $a Abou Zeid, Nuhad $u 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. $7 gn_A_00000666
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- $a Kale, Nilufer $u 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.
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- $a Tutuncu, Melih $u 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.
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- $a Crusan, Daniel J $u 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.
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- $a Atkinson, Elizabeth J $u 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. $7 gn_A_00009786
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- $a Siva, Aksel $u 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.
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- $a Keegan, B Mark $u 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.
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- $a Pirko, Istvan $u 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.
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- $a Pittock, Sean J $u 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.
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- $a Lucchinetti, Claudia F $u 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.
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- $a Weinshenker, Brian G $u 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.
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- $a Rodriguez, Moses $u 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.
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- $a Kantarci, Orhun H $u 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.
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