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1.
Lancet Neurol ; 19(4): 307-316, 2020 04.
Article in English | MEDLINE | ID: mdl-32199096

ABSTRACT

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 ≥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<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. 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. FUNDING: National Health and Medical Research Council Australia and MS Society UK.


Subject(s)
Multiple Sclerosis/therapy , Adult , Age of Onset , Cohort Studies , Databases, Factual , Disability Evaluation , Female , Follow-Up Studies , Humans , Male , Middle Aged , Propensity Score , Registries , Retrospective Studies , Sweden , Time-to-Treatment , Treatment Outcome
2.
Mult Scler ; 26(6): 679-687, 2020 05.
Article in English | MEDLINE | ID: mdl-30957691

ABSTRACT

BACKGROUND: In relapse-onset multiple sclerosis (MS), tissue abnormality - as assessed with magnetisation transfer ratio (MTR) imaging - is greater in the outer cortical and inner periventricular layers. The cause of this remains unknown but meningeal inflammation has been implicated, particularly lymphoid follicles, which are seen in secondary progressive (SP) but not primary progressive (PP) MS. Cortical and periventricular MTR gradients might, therefore, differ in PPMS and SPMS if these follicles are responsible. OBJECTIVE: We assessed cortical and periventricular MTR gradients in PPMS, and compared gradients between people with PPMS and SPMS. METHODS: Using an optimised processing pipeline, periventricular normal-appearing white matter and cortical grey-matter MTR gradients were compared between 51 healthy controls and 63 people with progressive MS (28 PPMS, 35 SPMS). RESULTS: The periventricular gradient was significantly shallower in healthy controls (0.122 percentage units (pu)/band) compared to PPMS (0.952 pu/band, p < 0.0001) and SPMS (1.360 pu/band, p < 0.0001). The cortical gradient was also significantly shallower in healthy controls (-2.860 pu/band) compared to PPMS (-3.214 pu/band, p = 0.038) and SPMS (-3.328 pu/band, p = 0.016). CONCLUSION: Abnormal periventricular and cortical MTR gradients occur in both PPMS and SPMS, suggesting comparable underlying pathological processes.


Subject(s)
Cerebral Cortex/pathology , Magnetic Resonance Imaging , Multiple Sclerosis, Chronic Progressive/pathology , White Matter/pathology , Adult , Cerebral Cortex/diagnostic imaging , Cohort Studies , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Multiple Sclerosis, Chronic Progressive/diagnostic imaging , Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging , Multiple Sclerosis, Relapsing-Remitting/pathology , White Matter/diagnostic imaging
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