Multiple sclerosis (MS) treatment intervention with immunomodulating therapy at early disease stage improves short term clinical outcomes. The objective of this study is to describe the long-term outcomes and healthcare utilization of patients with clinically isolated syndrome (CIS) included in the Betaferon®/Betaseron® in Newly Emerging MS for Initial Treatment (BENEFIT) randomized, parallel group trial. In BENEFIT patients were assigned to "early" IFNB-1b treatment or placebo ("delayed" treatment). After 2 years or conversion to clinically definite multiple sclerosis (CDMS), all patients were offered IFNB-1b and were reassessed 15 years later. Of 468 patients, 261 (55.8%) were enrolled into BENEFIT 15 (161 [55.1%] from the early, 100 [56.8%] from the delayed treatment arm). In the full BENEFIT analysis set, risk of conversion to CDMS remained lower in the early treatment group ( - 30.5%; hazard ratio 0.695 [95% CI, 0.547-0.883]; p = 0.0029) with a 15.7% lower risk of relapse than in the delayed treatment group (p = 0.1008). Overall, 25 patients (9.6%; 9.9% early, 9.0% delayed) converted to secondary progressive multiple sclerosis. Disability remained low and stable with no significant difference between groups in Expanded Disability Status Scale score or MRI metrics. Paced Auditory Serial Addition Task-3 scores were better in the early treatment group (p = 0.0036 for treatment effect over 15 years). 66.3% of patients were still employed at Year 15 versus 74.7% at baseline. In conclusion, results 15 years from initial randomization support long-term benefits of early treatment with IFNB-1b.

• MeSH
• demyelinizační nemoci farmakoterapie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• interferon beta 1b * terapeutické užití   farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• následné studie MeSH
• progrese nemoci MeSH
• roztroušená skleróza * farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

BACKGROUND AND OBJECTIVES: Serum neurofilament light chain (sNfL) levels correlate with multiple sclerosis (MS) disease activity, but the dynamics of this correlation are unknown. We evaluated the relationship between sNfL levels and radiologic MS disease activity through monthly assessments during the 24-week natalizumab treatment interruption period in RESTORE (NCT01071083). METHODS: In the RESTORE trial, participants with relapsing forms of MS who had received natalizumab for ≥12 months were randomized to either continue or stop natalizumab and followed with MRI and blood draws every 4 weeks to week 28 and again at week 52 The sNfL was measured, and its dynamics were correlated with the development of gadolinium-enhancing (Gd+) lesions. Log-linear trend in sNfL levels were modeled longitudinally using generalized estimating equations with robust variance estimator from baseline to week 28. RESULTS: Of 175 patients enrolled in RESTORE, 166 had serum samples for analysis. Participants with Gd+ lesions were younger (37.7 vs 43.1, p = 0.001) and had lower Expanded Disability Status Scale scores at baseline (2.7 vs 3.4, p = 0.017) than participants without Gd+ lesions. sNfL levels increased in participants with Gd+ lesions (n = 65) compared with those without (n = 101, mean change from baseline to maximum sNfL value, 12.1 vs 3.2 pg/mL, respectively; p = 0.003). As the number of Gd+ lesions increased, peak median sNfL change also increased by 1.4, 3.0, 4.3, and 19.6 pg/mL in the Gd+ lesion groups of 1 (n = 12), 2-3 (n = 18), 4-9 (n = 21), and ≥10 (n = 14) lesions, respectively. However, 46 of 65 (71%) participants with Gd+ lesions did not increase above the 95th percentile threshold of the group without Gd+ lesions. The initial increase of sNfL typically trailed the first observation of Gd+ lesions, and the peak increase in sNfL was a median [interquartile range] of 8 [0, 12] weeks after the first appearance of the Gd+ lesion. DISCUSSION: Although sNfL correlated with the presence of Gd+ lesions, most participants with Gd+ lesions did not have elevations in sNfL levels. These observations have implications for the use and interpretation of sNfL as a biomarker for monitoring MS disease activity in controlled trials and clinical practice.

• MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• dospělí MeSH
• gadolinium MeSH
• imunologické faktory terapeutické užití   krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• natalizumab * terapeutické užití   MeSH
• neurofilamentové proteiny * krev   MeSH
• posuzování pracovní neschopnosti MeSH
• progrese nemoci MeSH
• relabující-remitující roztroušená skleróza krev   farmakoterapie   diagnostické zobrazování   MeSH
• roztroušená skleróza krev   diagnostické zobrazování   farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Simultaneous comparisons of multiple disease-modifying therapies for relapsing-remitting multiple sclerosis (RRMS) over an extended follow-up are lacking. Here we emulate a randomised trial simultaneously comparing the effectiveness of six commonly used therapies over 5 years. METHODS: Data from 74 centres in 35 countries were sourced from MSBase. For each patient, the first eligible intervention was analysed, censoring at change/discontinuation of treatment. The compared interventions included natalizumab, fingolimod, dimethyl fumarate, teriflunomide, interferon beta, glatiramer acetate and no treatment. Marginal structural Cox models (MSMs) were used to estimate the average treatment effects (ATEs) and the average treatment effects among the treated (ATT), rebalancing the compared groups at 6-monthly intervals on age, sex, birth-year, pregnancy status, treatment, relapses, disease duration, disability and disease course. The outcomes analysed were incidence of relapses, 12-month confirmed disability worsening and improvement. RESULTS: 23 236 eligible patients were diagnosed with RRMS or clinically isolated syndrome. Compared with glatiramer acetate (reference), several therapies showed a superior ATE in reducing relapses: natalizumab (HR=0.44, 95% CI=0.40 to 0.50), fingolimod (HR=0.60, 95% CI=0.54 to 0.66) and dimethyl fumarate (HR=0.78, 95% CI=0.66 to 0.92). Further, natalizumab (HR=0.43, 95% CI=0.32 to 0.56) showed a superior ATE in reducing disability worsening and in disability improvement (HR=1.32, 95% CI=1.08 to 1.60). The pairwise ATT comparisons also showed superior effects of natalizumab followed by fingolimod on relapses and disability. CONCLUSIONS: The effectiveness of natalizumab and fingolimod in active RRMS is superior to dimethyl fumarate, teriflunomide, glatiramer acetate and interferon beta. This study demonstrates the utility of MSM in emulating trials to compare clinical effectiveness among multiple interventions simultaneously.

• MeSH
• dimethyl fumarát terapeutické užití   MeSH
• fingolimod hydrochlorid terapeutické užití   MeSH
• glatiramer acetát terapeutické užití   MeSH
• imunosupresiva terapeutické užití   MeSH
• interferon beta terapeutické užití   MeSH
• lidé MeSH
• natalizumab terapeutické užití   MeSH
• recidiva MeSH
• relabující-remitující roztroušená skleróza * farmakoterapie   MeSH
• roztroušená skleróza * farmakoterapie   MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Some studies comparing primary and secondary progressive multiple sclerosis (PPMS, SPMS) report similar ages at onset of the progressive phase and similar rates of subsequent disability accrual. Others report later onset and/or faster accrual in SPMS. Comparisons have been complicated by regional cohort effects, phenotypic differences in sex ratio and management and variable diagnostic criteria for SPMS. METHODS: We compared disability accrual in PPMS and operationally diagnosed SPMS in the international, clinic-based MSBase cohort. Inclusion required PPMS or SPMS with onset at age ≥18 years since 1995. We estimated Andersen-Gill hazard ratios for disability accrual on the Expanded Disability Status Scale (EDSS), adjusted for sex, age, baseline disability, EDSS score frequency and drug therapies, with centre and patient as random effects. We also estimated ages at onset of the progressive phase (Kaplan-Meier) and at EDSS milestones (Turnbull). Analyses were replicated with physician-diagnosed SPMS. RESULTS: Included patients comprised 1872 with PPMS (47% men; 50% with activity) and 2575 with SPMS (32% men; 40% with activity). Relative to PPMS, SPMS had older age at onset of the progressive phase (median 46.7 years (95% CI 46.2-47.3) vs 43.9 (43.3-44.4); p<0.001), greater baseline disability, slower disability accrual (HR 0.86 (0.78-0.94); p<0.001) and similar age at wheelchair dependence. CONCLUSIONS: We demonstrate later onset of the progressive phase and slower disability accrual in SPMS versus PPMS. This may balance greater baseline disability in SPMS, yielding convergent disability trajectories across phenotypes. The different rates of disability accrual should be considered before amalgamating PPMS and SPMS in clinical trials.

• MeSH
• chronicko-progresivní roztroušená skleróza * farmakoterapie   MeSH
• lidé MeSH
• postižení * MeSH
• progrese nemoci MeSH
• proporcionální rizikové modely MeSH
• roztroušená skleróza * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• farmakogenetika MeSH
• interferon alfa terapeutické užití   MeSH
• interferon beta terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• management nemoci MeSH
• roztroušená skleróza farmakoterapie   MeSH
• transplantace kmenových buněk MeSH
• Publikační typ
• sborníky MeSH

• Konspekt
• Farmacie. Farmakologie
• NLK Obory
• neurologie
• farmacie a farmakologie
• farmacie a farmakologie

• MeSH
• interferon beta terapeutické užití   MeSH
• magnetická rezonanční tomografie MeSH
• prognóza MeSH
• rehabilitace MeSH
• roztroušená skleróza terapie   MeSH
• Publikační typ
• sborníky MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• neurologie
• biochemie