RT Journal Article
T1 Defining secondary progressive multiple sclerosis.
A1 Lorscheider, Johannes
A1 Buzzard, Katherine
A1 Jokubaitis, Vilija
A1 Spelman, Tim
A1 Havrdova, Eva
A1 Horakova, Dana
A1 Trojano, Maria
A1 Izquierdo, Guillermo
A1 Girard, Marc
A1 Duquette, Pierre
A1 Prat, Alexandre
A1 Lugaresi, Alessandra
A1 Grand'Maison, François
A1 Grammond, Pierre
A1 Hupperts, Raymond
A1 Alroughani, Raed
A1 Sola, Patrizia
A1 Boz, Cavit
A1 Pucci, Eugenio
A1 Lechner-Scott, Jeanette
A1 Bergamaschi, Roberto
A1 Oreja-Guevara, Celia
A1 Iuliano, Gerardo
A1 Van Pesch, Vincent
A1 Granella, Franco
A1 Ramo-Tello, Cristina
A1 Spitaleri, Daniele
A1 Petersen, Thor
A1 Slee, Mark
A1 Verheul, Freek
A1 Ampapa, Radek
A1 Amato, Maria Pia
A1 McCombe, Pamela
A1 Vucic, Steve
A1 Sánchez Menoyo, José Luis
A1 Cristiano, Edgardo
A1 Barnett, Michael H
A1 Hodgkinson, Suzanne
A1 Olascoaga, Javier
A1 Saladino, Maria Laura
A1 Gray, Orla
A1 Shaw, Cameron
A1 Moore, Fraser
A1 Butzkueven, Helmut
A1 Kalincik, Tomas
A1 MSBase Study Group, 
K1 MSBase
K1 definition
K1 disability
K1 secondary progressive multiple sclerosis
K1 study design
AB 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.
YR 2016
FD 2016-07-07
LK http://hdl.handle.net/10668/10256
UL http://hdl.handle.net/10668/10256
LA en
DS RISalud
RD Apr 4, 2025