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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F20%3A10411419" target="_blank" >RIV/00216208:11110/20:10411419 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064165:_____/20:10411419

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=vmn4G-a0rr" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=vmn4G-a0rr</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/S1474-4422(20)30067-3" target="_blank" >10.1016/S1474-4422(20)30067-3</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

Background: 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. Methods: 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 &gt;=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. Findings: 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&lt;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&lt;0.0001), with a difference between groups of -0.98 (95% CI -1.51 to -0.45; p&lt;0.0001, adjusted for proportion of time on any disease-modifying therapy) across the 6-10 year follow-up period. Interpretation: 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.

Název v anglickém jazyce

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

Popis výsledku anglicky

Background: 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. Methods: 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 &gt;=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. Findings: 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&lt;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&lt;0.0001), with a difference between groups of -0.98 (95% CI -1.51 to -0.45; p&lt;0.0001, adjusted for proportion of time on any disease-modifying therapy) across the 6-10 year follow-up period. Interpretation: 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

The Lancet: Neurology

ISSN

1474-4422

e-ISSN

—

Svazek periodika

19

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

307-316

Kód UT WoS článku

000520920500017

EID výsledku v databázi Scopus

2-s2.0-85081694735