Predictors of long-term disability accrual in relapse-onset multiple sclerosis

Vilija G. Jokubaitis, Tim Spelman, Tomas Kalincik, Johannes Lorscheider, Eva Havrdova, Dana Horakova, Pierre Duquette, Marc Girard, Alexandre Prat, Guillermo Izquierdo, Pierre Grammond, Vincent Van Pesch, Eugenio Pucci, François Grand'Maison, Raymond Hupperts, Franco Granella, Patrizia Sola, Roberto Bergamaschi, Gerardo Iuliano, Daniele SpitaleriCavit Boz, Suzanne Hodgkinson, Javier Olascoaga, Freek Verheul, Pamela McCombe, Thor Petersen, Csilla Rozsa, Jeannette Lechner-Scott, Maria Laura Saladino, Deborah Farina, Pietro Iaffaldano, Damiano Paolicelli, Helmut Butzkueven, Alessandra Lugaresi, Maria Trojano

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Abstract

Objective: To identify predictors of 10-year Expanded Disability Status Scale (EDSS) change after treatment initiation in patients with relapse-onset multiple sclerosis. Methods: Using data obtained from MSBase, we defined baseline as the date of first injectable therapy initiation. Patients need only have remained on injectable therapy for 1 day and were monitored on any approved disease-modifying therapy, or no therapy thereafter. Median EDSS score changes over a 10-year period were determined. Predictors of EDSS change were then assessed using median quantile regression analysis. Sensitivity analyses were further performed. Results: We identified 2,466 patients followed up for at least 10 years reporting post-baseline disability scores. Patients were treated an average 83% of their follow-up time. EDSS scores increased by a median 1 point (interquartile range = 0–2) at 10 years post-baseline. Annualized relapse rate was highly predictive of increases in median EDSS over 10 years (coeff = 1.14, p = 1.9 × 10−22). On-therapy relapses carried greater burden than off-therapy relapses. Cumulative treatment exposure was independently associated with lower EDSS at 10 years (coeff = −0.86, p = 1.3 × 10−9). Furthermore, pregnancies were also independently associated with lower EDSS scores over the 10-year observation period (coeff = −0.36, p = 0.009). Interpretation: We provide evidence of long-term treatment benefit in a large registry cohort, and provide evidence of long-term protective effects of pregnancy against disability accrual. We demonstrate that high annualized relapse rate, particularly on-treatment relapse, is an indicator of poor prognosis. Ann Neurol 2016;80:89–100.

Original languageEnglish
Pages (from-to)89-100
Number of pages12
JournalAnnals of Neurology
Volume80
Issue number1
DOIs
Publication statusPublished - Jul 1 2016

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ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Jokubaitis, V. G., Spelman, T., Kalincik, T., Lorscheider, J., Havrdova, E., Horakova, D., Duquette, P., Girard, M., Prat, A., Izquierdo, G., Grammond, P., Van Pesch, V., Pucci, E., Grand'Maison, F., Hupperts, R., Granella, F., Sola, P., Bergamaschi, R., Iuliano, G., ... Trojano, M. (2016). Predictors of long-term disability accrual in relapse-onset multiple sclerosis. Annals of Neurology, 80(1), 89-100. https://doi.org/10.1002/ana.24682