Article Text

The natural history of secondary progressive multiple sclerosis
  1. Marcus Koch1,2,
  2. Elaine Kingwell1,
  3. Peter Rieckmann1,
  4. Helen Tremlett1,
  5. UBC MS Clinic Neurologists
  1. 1Faculty of Medicine, Division of Neurology, University of British Columbia, Vancouver, Canada
  2. 2Department of Neurology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
  1. Correspondence to Dr M Koch, Department of Neurology, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; m.w.koch{at}


Background The onset of secondary progression is a pivotal event in the course of relapsing–remitting (RR) multiple sclerosis (MS). Patients with secondary progressive MS (SPMS) experience continuous worsening of symptoms independent of the occurrence of relapses. Possible risk factors associated with the onset of SPMS remain under investigated in natural history studies of MS disease course.

Methods We used Kaplan–Meier survival analyses and Cox regression models to investigate the influence of gender, onset age and onset symptoms on time to and age at SPMS in British Columbia (BC) MS patients with a RR disease onset who were not exposed to immunomodulatory drugs.

Results Of 5778 patients in the BCMS database with definite MS, 5207 (90%) had an RR onset. Median time to SPMS was 21.4 years (95% CI 20.6 to 22.2), reached at a median age of 53.7 years (95% CI 53.1 to 54.3). Male gender and motor onset symptoms were associated with a shorter time to and a younger age at SPMS. A younger age at disease onset was associated with a longer time to SPMS but also with a younger age at secondary progression. Other onset symptoms were not associated with time to, or age at, SPMS.

Conclusions We identified three factors influencing the onset of SPMS in untreated patients with RRMS: motor onset symptoms and male gender were associated with both a shorter time to and a younger age at SPMS. A younger age at disease onset should not be viewed as indicating a better prognosis.

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Supplementary materials


  • UBC MS Neurologists: D Adams, D Craig, L Daly, V Devonshire, S Hashimoto, O Hrebicek, J Hooge, B Jones, L Kastrukoff, S Meckling, J Oger, D Parton, D Paty, P Smyth, W Shtybel, T Traboulsee.

  • Funding MK received research support from a Canadian Institutes of Health Research (CIHR) Fellowship and a Du Pré Grant from the MS International Federation (MSIF, EK is funded by an MS Society of Canada Post-doctoral Fellowship. PR serves as Research Chair of the MS Society of Canada, serves on scientific advisory boards for the Germany MS Society and receives research support from the MS Society of Canada, the US National MS Society and the CIHR. HT received research support from the CIHR (190898 (PI) and MOP-82738 (PI)), the US National MS Society and the MS Society of Canada (Don Paty Career Development Award), and is a Michael Smith Foundation for Health Research Scholar. The BCMS database was funded by an unrestricted grant from Dr Donald Paty and the MS/MRI Research Group.

  • Competing interests PR serves on scientific advisory boards for Merck Serono, Novartis, Teva Pharmaceutical Industries Ltd and Bayer-Schering Pharma. He also serves on the editorial advisory board of Therapeutics in Neurology and has received speaker and/or consulting honoraria from Bayer-Schering Pharma, Biogen Idec, Merck Serono, Novartis and Teva Pharmaceutical Industries Ltd. HT has received speaker honoraria from the Swiss MS Society and the University of British Columbia MS Research Program.

  • Ethics approval The study was approved by the clinical research ethics board of the University of British Columbia.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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