Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis

J. William L. Brown, Alasdair Coles, Dana Horakova, Eva Havrdova, Guillermo Izquierdo, Alexandre Prat, Marc Girard, Pierre Duquette, Maria Trojano, Alessandra Lugaresi, Roberto Bergamaschi, Pierre Grammond, Raed Alroughani, Raymond Hupperts, Pamela McCombe, Vincent Van Pesch, Patrizia Sola, Diana Ferraro, Francois Grand'Maison, Murat TerziJeannette Lechner-Scott, Schlomo Flechter, Mark Slee, Vahid Shaygannejad, Eugenio Pucci, Franco Granella, Vilija Jokubaitis, Mark Willis, Claire Rice, Neil Scolding, Alastair Wilkins, Owen R. Pearson, Tjalf Ziemssen, Michael Hutchinson, Katharine Harding, Joanne Jones, Christopher McGuigan, Helmut Butzkueven, Tomas Kalincik*, Neil Robertson, Marco Onofrj, Giovanna De Luca, Valeria Di Tommaso, Daniela Travaglini, Erika Pietrolongo, Maria di Ioia, Deborah Farina, Luca Mancinelli, Suzanne Hodgkinson, Celia Oreja-Guevara, MSBase Study Grp

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


IMPORTANCE Within 2 decades of onset, 80% of untreated patients with relapsing-remitting multiple sclerosis (MS) convert to a phase of irreversible disability accrual termed secondary progressiveMS. The association between disease-modifying treatments (DMTs), and this conversion has rarely been studied and never using a validated definition.

OBJECTIVE To determine the association between the use, the type of, and the timing of DMTs with the risk of conversion to secondary progressive MS diagnosed with a validated definition.

DESIGN, SETTING, AND PARTICIPANTS Cohort study with prospective data from 68 neurology centers in 21 countries examining patients with relapsing-remittingMS commencing DMTs (or clinical monitoring) between 1988-2012 with minimum 4 years' follow-up.

EXPOSURES The use, type, and timing of the following DMTs: interferon beta, glatiramer acetate, fingolimod, natalizumab, or alemtuzumab. After propensity-score matching, 1555 patients were included (last follow-up, February 14, 2017).

MAIN OUTCOME AND MEASURE Conversion to objectively defined secondary progressiveMS.

RESULTS Of the 1555 patients, 1123 were female (mean baseline age, 35 years [SD, 10]). Patients initially treated with glatiramer acetate or interferon beta had a lower hazard of conversion to secondary progressiveMS than matched untreated patients (HR, 0.71; 95% CI, 0.61-0.81; P

CONCLUSIONS AND RELEVANCE Among patients with relapsing-remittingMS, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion to secondary progressiveMS vs initial treatment with glatiramer acetate or interferon beta. These findings, considered along with these therapies' risks, may help inform decisions about DMT selection.

Original languageEnglish
Pages (from-to)175-187
Number of pages13
JournalJAMA-Journal of the American Medical Association
Issue number2
Publication statusPublished - 15 Jan 2019


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