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Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study.

Artikel i vetenskaplig tidskrift
Författare Anna He
Bernd Merkel
James William L Brown
Lana Zhovits Ryerson
Ilya Kister
Charles B Malpas
Sifat Sharmin
Dana Horakova
Eva Kubala Havrdova
Tim Spelman
Guillermo Izquierdo
Sara Eichau
Maria Trojano
Alessandra Lugaresi
Raymond Hupperts
Patrizia Sola
Diana Ferraro
Jan Lycke
Francois Grand'Maison
Alexandre Prat
Marc Girard
Pierre Duquette
Catherine Larochelle
Anders Svenningsson
Thor Petersen
Pierre Grammond
Franco Granella
Vincent Van Pesch
Roberto Bergamaschi
Christopher McGuigan
Alasdair Coles
Jan Hillert
Fredrik Piehl
Helmut Butzkueven
Tomas Kalincik
Publicerad i The Lancet. Neurology
Volym 19
Nummer/häfte 4
Sidor 307-316
ISSN 1474-4465
Publiceringsår 2020
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap
Sidor 307-316
Språk en
Länkar dx.doi.org/10.1016/S1474-4422(20)30...
Ämneskategorier Neurovetenskaper, Neurologi


High-efficacy therapies in multiple sclerosis are traditionally used after unsuccessful treatment with first-line disease modifying therapies. We hypothesised that early commencement of high-efficacy therapy would be associated with reduced long-term disability. We therefore aimed to compare long-term disability outcomes between patients who started high-efficacy therapies within 2 years of disease onset with those who started 4-6 years after disease onset.In this retrospective international observational study, we obtained data from the MSBase registry and the Swedish MS registry, which prospectively collect patient data that are specific to multiple sclerosis as part of routine clinical care. We identified adult patients (aged ≥18 years) with relapsing-remitting multiple sclerosis, with at least 6 years of follow-up since disease onset, and who started the high-efficacy therapy (rituximab, ocrelizumab, mitoxantrone, alemtuzumab, or natalizumab) either 0-2 years (early) or 4-6 years (late) after clinical disease onset. We matched patients in the early and late groups using propensity scores calculated on the basis of their baseline clinical and demographic data. The primary outcome was disability, measured with the Expanded Disability Status Score (EDSS; an ordinal scale of 0-10, with higher scores indicating increased disability), at 6-10 years after disease onset, assessed with a linear mixed-effects model.We identified 6149 patients in the MSBase registry who had been given high-efficacy therapy, with data collected between Jan 1, 1975, and April 13, 2017, and 2626 patients in the Swedish MS Registry, with data collected between Dec 10, 1997, and Sept 16, 2019. Of whom, 308 in the MSBase registry and 236 in the Swedish MS registry were eligible for inclusion. 277 (51%) of 544 patients commenced therapy early and 267 (49%) commenced therapy late. For the primary analysis, we matched 213 patients in the early treatment group with 253 in the late treatment group. At baseline, the mean EDSS score was 2·2 (SD 1·2) in the early group and 2·1 (SD 1·2) in the late group. Median follow-up time for matched patients was 7·8 years (IQR 6·7-8·9). In the sixth year after disease onset, the mean EDSS score was 2·2 (SD 1·6) in the early group compared with 2·9 (SD 1·8) in the late group (p<0·0001). This difference persisted throughout each year of follow-up until the tenth year after disease onset (mean EDSS score 2·3 [SD 1·8] vs 3·5 [SD 2·1]; p<0·0001), with a difference between groups of -0·98 (95% CI -1·51 to -0·45; p<0·0001, adjusted for proportion of time on any disease-modifying therapy) across the 6-10 year follow-up period.High-efficacy therapy commenced within 2 years of disease onset is associated with less disability after 6-10 years than when commenced later in the disease course. This finding can inform decisions regarding optimal sequence and timing of multiple sclerosis therapy.National Health and Medical Research Council Australia and MS Society UK.

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