BACKGROUND: Aggressive disease control soon after multiple sclerosis (MS) diagnosis may prevent irreversible neurological damage, and therefore early initiation of a high-efficacy disease-modifying therapy (DMT) is of clinical relevance. OBJECTIVES: Evaluate long-term clinical outcomes in patients with MS who initiated treatment with either natalizumab or a BRACETD therapy (interferon beta, glatiramer acetate, teriflunomide, or dimethyl fumarate). DESIGN: This retrospective analysis utilized data from MSBase to create a matched population allowing comparison of first-line natalizumab to first-line BRACETD. METHODS: This study included patients who initiated treatment either with natalizumab or a BRACETD DMT within 1 year of MS diagnosis and continued treatment for ⩾6 months, after which patients could switch DMTs or discontinue treatment. Patients had a minimum follow-up time of ⩾60 months from initiation. A subgroup analysis compared the natalizumab group to patients in the BRACETD group who escalated therapy after 6 months. Outcomes included unadjusted annualized relapse rates (ARRs), time-to-first relapse, time-to-first confirmed disability improvement (CDI), and time-to-first confirmed disability worsening (CDW). RESULTS: After 1:1 propensity score matching, 355 BRACETD patients were matched to 355 natalizumab patients. Patients initiating natalizumab were less likely to experience a relapse over the duration of follow-up, with ARRs [95% confidence interval (CI)] of 0.080 (0.070-0.092) for natalizumab patients and 0.191 (0.178-0.205) for BRACETD patients (p < 0.0001). A Cox regression model of time-to-first relapse showed a reduced risk of relapse for natalizumab patients [hazard ratio (95% CI) of 0.52 (0.42-0.65); p < 0.001] and a more favorable time-to-first CDI. The risk of CDW was similar between groups. The subgroup analysis showed an increased relapse risk as well as a significantly higher risk of CDW for BRACETD patients. CONCLUSION: Early initiation of natalizumab produced long-term benefits in relapse outcomes in comparison with BRACETD, regardless of a subsequent escalation in therapy.

• Klíčová slova
• multiple sclerosis, natalizumab, real-world evidence,
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND PURPOSE: This study assessed the effect of patient characteristics on the response to disease-modifying therapy (DMT) in multiple sclerosis (MS). METHODS: We extracted data from 61,810 patients from 135 centers across 35 countries from the MSBase registry. The selection criteria were: clinically isolated syndrome or definite MS, follow-up ≥ 1 year, and Expanded Disability Status Scale (EDSS) score ≥ 3, with ≥1 score recorded per year. Marginal structural models with interaction terms were used to compare the hazards of 12-month confirmed worsening and improvement of disability, and the incidence of relapses between treated and untreated patients stratified by their characteristics. RESULTS: Among 24,344 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.45-0.60), 46% lower risk of disability worsening (HR = 0.54, 95% CI = 0.41-0.71), and 32% greater chance of disability improvement (HR = 1.32, 95% CI = 1.09-1.59). The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The magnitude of the effect of DMT on suppressing relapses declined with higher prior relapse rate and prior cerebral magnetic resonance imaging activity. We did not find any evidence for the effect of age on the effectiveness of DMT. After inclusion of 1985 participants with progressive MS, the effect of DMT on disability mostly depended on MS phenotype, whereas its effect on relapses was driven mainly by prior relapse activity. CONCLUSIONS: DMT is generally most effective among patients with lower disability and in relapsing MS phenotypes. There is no evidence of attenuation of the effect of DMT with age.

• Klíčová slova
• EDSS, immunotherapy, marginal structural model, multiple sclerosis, relapse,
• MeSH
• chronicko-progresivní roztroušená skleróza * MeSH
• imunoterapie MeSH
• lidé MeSH
• proporcionální rizikové modely MeSH
• recidiva MeSH
• relabující-remitující roztroušená skleróza * MeSH
• roztroušená skleróza * terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Fingolimod, an oral sphingosine 1-phosphate receptor immunomodulator, is approved in Europe for people with multiple sclerosis (pwMS) with highly active disease despite a full and adequate course of treatment with ≥ 1 disease-modifying therapy or patients with rapidly evolving severe relapsing-remitting MS. GOLEMS, a national, multicenter, non-interventional, single-arm, real-world study showed a favorable benefit-risk profile of 12-month treatment with fingolimod in pwMS in the Czech Republic. Here, we evaluated the long-term effectiveness and safety of fingolimod and its impact on disability progression and work capability for up to 48 months in pwMS. METHODS: The endpoints assessed were the incidence and severity of MS relapses in fingolimod-treated patients and the proportion of relapse-free patients up to 48 months of fingolimod treatment, change from baseline in the Expanded Disability Status Scale (EDSS) score, and change from baseline in work capability assessment. Efficacy outcomes were analyzed in the completed and efficacy sets, and safety was evaluated in all the enrolled patients. RESULTS: Of 240 enrolled patients, 237 were included into efficacy set. Patients with a minimum of a 12-month observation period in the core study who continued fingolimod treatment, were eligible to participate in the extension phase. Of 211 patients enrolled in extension study, 155 were evaluated in the completed set. Based on analysis of 48-month period of fingolimod treatment, 95/237 patients (40.1%) in the efficacy set, 54/155 (34.8%) in the completed set were free of relapses. The majority of relapses reported were moderate in intensity. Mean EDSS score remained stable throughout 48-month study period (Baseline, 3.4; Month 48, 3.6). No trend was observed in changes in work capability assessment or number of missed days of work. Of 240 enrolled patients, 147 (61.3%) had ≥ 1 treatment-emergent adverse event (AE) and 20 (8.3%) reported serious AEs. In total, 45 patients (18.8%) permanently discontinued treatment because of AEs related to study drug; two patients reported pregnancy after treatment initiation and subsequently discontinued the treatment; no deaths were reported. CONCLUSION: GOLEMS study demonstrated the sustained effectiveness and manageable safety profile of fingolimod under real-world conditions over 48 months in patients with MS. TRIAL REGISTRATION: Not applicable.

• Klíčová slova
• EDSS score, Fingolimod, GOLEMS extension study, Multiple sclerosis, Relapse,
• MeSH
• fingolimod hydrochlorid * škodlivé účinky   terapeutické užití   MeSH
• imunosupresiva * škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• recidiva MeSH
• relabující-remitující roztroušená skleróza farmakoterapie   epidemiologie   MeSH
• roztroušená skleróza * farmakoterapie   epidemiologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• fingolimod hydrochlorid * MeSH
• imunosupresiva * MeSH

BACKGROUND: Time matters in multiple sclerosis (MS). Irreversible neural damage and cell loss occur from disease onset. The MS community has endorsed a management strategy of prompt diagnosis, timely intervention and regular proactive monitoring of treatment effectiveness and disease activity to improve outcomes in people with MS. OBJECTIVES: We sought to develop internationally applicable quality standards for timely, brain health-focused MS care. METHODS: A panel of MS specialist neurologists participated in an iterative, online, modified Delphi process to define 'core', 'achievable' and 'aspirational' time frames reflecting minimum, good and high care standards, respectively. A multidisciplinary Reviewing Group (MS nurses, people with MS, allied healthcare professionals) provided insights ensuring recommendations reflected perspectives from multiple stakeholders. RESULTS: Twenty-one MS neurologists from 19 countries reached consensus on most core (25/27), achievable (25/27) and aspirational (22/27) time frames at the end of five rounds. Agreed standards cover six aspects of the care pathway: symptom onset, referral and diagnosis, treatment decisions, lifestyle, disease monitoring and managing new symptoms. CONCLUSION: These quality standards for core, achievable and aspirational care provide MS teams with a three-level framework for service evaluation, benchmarking and improvement. They have the potential to produce a profound change in the care of people with MS.

• Klíčová slova
• Delphi technique, Multiple sclerosis, benchmarking, consensus, quality improvement, standards,
• MeSH
• delfská metoda MeSH
• konsensus MeSH
• lidé MeSH
• mozek * patologie   MeSH
• neurologie normy   MeSH
• roztroušená skleróza * diagnóza   patologie   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH