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Abstract

Background:

The risk factors for conversion from relapsing-remitting to secondary progressive multiple sclerosis remain highly contested.

Objective:

The aim of this study was to determine the demographic, clinical and paraclinical features that influence the risk of conversion to secondary progressive multiple sclerosis.

Methods:

Patients with adult-onset relapsing–remitting multiple sclerosis and at least four recorded disability scores were selected from MSBase, a global observational cohort. The risk of conversion to objectively defined secondary progressive multiple sclerosis was evaluated at multiple time points per patient using multivariable marginal Cox regression models. Sensitivity analyses were performed.

Results:

A total of 15,717 patients were included in the primary analysis. Older age (hazard ratio (HR) = 1.02, p < 0.001), longer disease duration (HR = 1.01, p = 0.038), a higher Expanded Disability Status Scale score (HR = 1.30, p < 0.001), more rapid disability trajectory (HR = 2.82, p < 0.001) and greater number of relapses in the previous year (HR = 1.07, p = 0.010) were independently associated with an increased risk of secondary progressive multiple sclerosis. Improving disability (HR = 0.62, p = 0.039) and disease-modifying therapy exposure (HR = 0.71, p = 0.007) were associated with a lower risk. Recent cerebral magnetic resonance imaging activity, evidence of spinal cord lesions and oligoclonal bands in the cerebrospinal fluid were not associated with the risk of conversion.

Conclusion:

Risk of secondary progressive multiple sclerosis increases with age, duration of illness and worsening disability and decreases with improving disability. Therapy may delay the onset of secondary progression.

Keywords

SPMS multiple sclerosis disease modifying therapies prediction prognostics

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References

Brown

JWL

Coles

Horakova

, et al. Association of initial disease-modifying therapy with later conversion to secondary progressive multiple sclerosis. JAMA 2019; 321(2): 175–187.

Lublin

Reingold

Cohen

, et al. Defining the clinical course of multiple sclerosis: The 2013 revisions. Neurology 2014; 83: 278–286.

Lorscheider

Buzzard

Jokubaitis

, et al. Defining secondary progressive multiple sclerosis. Neurology 2017; 139(Pt 9): 2395–2405.

Butzkueven

Chapman

Cristiano

, et al. MSBase: An international, online registry and platform for collaborative outcomes research in multiple sclerosis. Mult Scler 2006; 12(6): 769–774.

Kalincik

Kuhle

Pucci

, et al. Data quality evaluation for observational multiple sclerosis registries. Mult Scler 2017; 23(5): 647–655.

Polman

Reingold

Banwell

, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69(2): 292–302.

Polman

Reingold

Edan

, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the ‘McDonald Criteria’. Ann Neurol 2005; 58(6): 840–846.

Skoog

Tedeholm

Runmarker

, et al. Continuous prediction of secondary progression in the individual course of multiple sclerosis. Mult Scler Relat Disord 2014; 3(5): 584–592.

Scalfari

Neuhaus

Daumer

, et al. Early relapses, onset of progression, and late outcome in multiple sclerosis. JAMA Neurol 2013; 70(2): 214–222.

10.

Bergamaschi

Berzuini

Romani

, et al. Predicting secondary progression in relapsing–remitting multiple sclerosis: A Bayesian analysis. J Neurol Sci 2001; 189(1–2): 13–21.

11.

Koch

Kingwell

Rieckmann

, et al. The natural history of secondary progressive multiple sclerosis. J Neurol Neurosurg Psychiatry 2010; 81: 1039–1043.

12.

Daumer

Griffith

Meister

, et al. Survival, and time to an advanced disease state or progression, of untreated patients with moderately severe MS in a multicenter observational database: Relevance for design of a clinical trial for high dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation. Mult Scler 2006; 12: 174–179.

13.

Held

Heigenhauser

Shang

, et al. Predictors of relapse rate in MS clinical trials. Neurology 2005; 65(11): 1769–1773.

14.

Kalincik

Vivek

Jokubaitis

, et al. Sex as a determinant of relapse incidence and progressive course of multiple sclerosis. Brain 2013; 136(Pt 12): 3609–3617.

15.

Rovaris

Confavreux

Furlan

, et al. Secondary progressive multiple sclerosis: Current knowledge and future challenges. Lancet Neurol 2006; 5(4): 343–354.

16.

Vukusic

Confavreux

Prognostic factors for progression of disability in the secondary progressive phase of multiple sclerosis. J Neurol Sci 2003; 206(2): 135–137.

17.

Koch

Uyttenboogaart

vanHarten

, et al. Factors associated with the risk of secondary progression in multiple sclerosis. Mult Scler 2008; 14(6): 799–803.

18.

Stankoff

Mrejen

Tourbah

, et al. Age at onset determines the occurrence of the progressive phase of multiple sclerosis. Neurology 2007; 68(10): 779–781.

19.

Scalfari

Neuhaus

Daumer

, et al. Onset of secondary progressive phase and long-term evolution of multiple sclerosis. J Neurol Neurosurg Psychiatry 2014; 85(1): 67–75.

20.

Tremlett

Yousefi

Devonshire

, et al. Impact of multiple sclerosis relapses on progression diminishes with time. Neurology 2009; 73(20): 1616–1623.

21.

Kremenchutzky

Rice

Baskerville

, et al. The natural history of multiple sclerosis: A geographically based study 9: Observations on the progressive phase of the disease. Brain 2006; 129(Pt 3): 584–594.

22.

Scalfari

Lederer

Daumer

, et al. The relationship of age with the clinical phenotype in multiple sclerosis. Mult Scler 2016; 22(13): 1750–1758.

23.

Alroughani

Akhtar

Ahmed

, et al. Clinical predictors of disease progression in multiple sclerosis patients with relapsing onset in a nation-wide cohort. Int J Neurosci 2015; 125(11): 831–837.

24.

Tedeholm

Skoog

Lisovskaja

, et al. The outcome spectrum of multiple sclerosis: Disability, mortality, and a cluster of predictors from onset. J Neurol 2015; 262(5): 1148–1163.

25.

Langer-Gould

Popat

Huang

, et al. Clinical and demographic predictors of long-term disability in patients with relapsing-remitting multiple sclerosis: A systematic review. Arch Neurol 2006; 63(12): 1686–1691.

26.

Novotna

Paz Soldan

Abou Zeid

, et al. Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis. Neurology 2015; 85: 722–729.

27.

Eriksson

Andersen

Runmarker

Long-term follow up of patients with clinically isolated syndromes, relapsing-remitting and secondary progressive multiple sclerosis

Mult Scler 2003; 9: 260–274.

28.

Zhang

Shirani

Zhao

, et al. Beta-interferon exposure and onset of secondary progressive multiple sclerosis. Eur J Neurol 2015; 22(6): 990–1000.

29.

Ebers

Traboulsee

, et al. Analysis of clinical outcomes according to original treatment groups 16 years after the pivotal IFNB-1b trial. J Neurol Neurosurg Psychiatry 2010; 81(8): 907–912.

30.

Signori

Gallo

Bovis

, et al. Long-term impact of interferon or Glatiramer acetate in multiple sclerosis: A systematic review and meta-analysis. Mult Scler Relat Disord 2016; 6: 57–63.

31.

Bergamaschi

Quaglini

Tavazzi

, et al. Immunomodulatory therapies delay disease progression in multiple sclerosis. Mult Scler 2016; 22(13): 1732–1740.

32.

Tedeholm

Lycke

Skoog

, et al. Time to secondary progression in patients with multiple sclerosis who were treated with first generation immunomodulating drugs. Mult Scler 2013; 19(6): 765–774.

33.

Ebers

Koopman

Hader

, et al. The natural history of multiple sclerosis: A geographically based study 8: Familial multiple sclerosis. Brain 2000; 123(Pt 3): 641–649.

34.

Cree

Gourraud

Oksenberg

, et al. Long-term evolution of multiple sclerosis disability in the treatment era. Ann Neurol 2016; 80(4): 499–510.

35.

Tintore

Rovira

Rio

, et al. Defining high, medium and low impact prognostic factors for developing multiple sclerosis. Brain 2015; 138(Pt 7): 1863–1874.

36.

Mostert

deGroot

Ramsaransing

, et al. Relationship between the extent of T2 lesions and the onset of secondary progression in multiple sclerosis. Eur J Neurol 2007; 14(11): 1210–1215.

37.

Brownlee

Altmann

Prados

, et al. Early imaging predictors of long-term outcomes in relapse-onset multiple sclerosis. Brain. 2019; 142: 2276–2287.

38.

Kalincik

Butzkueven

Observational data: Understanding the real MS world. Mult Scler 2016; 22(13): 1642–1648.

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Risk of secondary progressive multiple sclerosis: A longitudinal study

Abstract

Background:

Objective:

Methods:

Results:

Conclusion:

Keywords

Get full access to this article

References

Supplementary Material