Defining secondary progressive multiple sclerosis

Johannes Lorscheider, Katherine Buzzard, Vilija G Jokubaitis, Tim Spelman, Eva Havrdova, Dana Horakova, Maria Trojano, Guillermo Izquierdo, Marc Girard, Pierre Pascal Duquette, Alexandre Prat, Alessandra Lugaresi, François Grand'maison, Pierre Grammond, Raymond Hupperts, Raed A Alroughani, Patrizia Sola, Cavit Boz, Eugenio Pucci, Jeanette Lechner-ScottRoberto Bergamaschi, Celia Oreja-Guevara, Gerardo Iuliano, Vincent Van Pesch, Franco Granella, Cristina Ramo-Tello, Daniele La Spitaleri, Thor Petersen, Mark Slee, Freek Verheul, Radek Ampapa, Maria Pia Amato, Pamela A McCombe, Steve Vucic, José Luis Sánchez Menoyo, Edgardo Cristiano, Michael H. Barnett, Suzanne J Hodgkinson, Javier Olascoaga, Maria Laura Saladino, Orla M Gray, Cameron Shaw, Fraser G A Moore, Helmut Butzkueven, Tomas Kalincik

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78 Citations (Scopus)


A number of studies have been conducted with the onset of secondary progressive multiple sclerosis as an inclusion criterion or an outcome of interest. However, a standardized objective definition of secondary progressive multiple sclerosis has been lacking. The aim of this work was to evaluate the accuracy and feasibility of an objective definition for secondary progressive multiple sclerosis, to enable comparability of future research studies. Using MSBase, a large, prospectively acquired, global cohort study, we analysed the accuracy of 576 data-derived onset definitions for secondary progressive multiple sclerosis and first compared these to a consensus opinion of three neurologists. All definitions were then evaluated against 5-year disease outcomes post-assignment of secondary progressive multiple sclerosis: sustained disability, subsequent sustained progression, positive disability trajectory, and accumulation of severe disability. The five best performing definitions were further investigated for their timeliness and overall disability burden. A total of 17 356 patients were analysed. The best definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step ≥4 and pyramidal score ≥2. It reached an accuracy of 87% compared to the consensus diagnosis. Seventy-eight per cent of the identified patients showed a positive disability trajectory and 70% reached significant disability after 5 years. The time until half of all patients were diagnosed was 32.6 years (95% confidence interval 32-33.6) after disease onset compared with the physicians' diagnosis at 36 (35-39) years. The identified patients experienced a greater disease burden [median annualized area under the disability-time curve 4.7 (quartiles 3.6, 6.0)] versus non-progressive patients [1.8 (1.2, 1.9)]. This objective definition of secondary progressive multiple sclerosis based on the Expanded Disability Status Scale and information about preceding relapses provides a tool for a reproducible, accurate and timely diagnosis that requires a very short confirmation period. If applied broadly, the definition has the potential to strengthen the design and improve comparability of clinical trials and observational studies in secondary progressive multiple sclerosis.

Original languageEnglish
Pages (from-to)2395-2405
Number of pages11
Issue number9
Publication statusPublished - 1 Sep 2016


  • definition
  • disability
  • MSBase
  • secondary progressive multiple sclerosis
  • study design

Cite this

Lorscheider, J., Buzzard, K., Jokubaitis, V. G., Spelman, T., Havrdova, E., Horakova, D., Trojano, M., Izquierdo, G., Girard, M., Duquette, P. P., Prat, A., Lugaresi, A., Grand'maison, F., Grammond, P., Hupperts, R., Alroughani, R. A., Sola, P., Boz, C., Pucci, E., ... Kalincik, T. (2016). Defining secondary progressive multiple sclerosis. Brain, 139(9), 2395-2405.