Treatment of Multiple Sclerosis: A Review

The American Journal of Medicine, Journal Year: 2020, Volume and Issue: 133(12), P. 1380 - 1390.e2

Published: July 17, 2020

Language: Английский

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Multiple sclerosis progression: time for a new mechanism-driven framework

The Lancet Neurology, Journal Year: 2022, Volume and Issue: 22(1), P. 78 - 88

Published: Nov. 18, 2022

Language: Английский

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How patients with multiple sclerosis acquire disability

Brain, Journal Year: 2022, Volume and Issue: 145(9), P. 3147 - 3161

Published: Jan. 28, 2022

Patients with multiple sclerosis acquire disability either through relapse-associated worsening (RAW) or progression independent of relapse activity (PIRA). This study addresses the relative contribution relapses to over course disease, how early begins and extent which therapies delay accumulation. Using Novartis-Oxford (NO.MS) data pool spanning all phenotypes paediatric sclerosis, we evaluated ∼200 000 Expanded Disability Status Scale (EDSS) transitions from >27 patients ≤15 years follow-up. We analysed three datasets: (i) A full analysis dataset containing observational randomized controlled clinical trials in were assessed (n = 27 328); (ii) phase 3 8346); (iii) placebo-controlled 4970). determined importance RAW PIRA, investigated role on all-cause using Andersen-Gill models observed impact mechanism disease-modifying time reach milestone levels continuous Markov models. PIRA started disease process, occurred became principal driver accumulation progressive disease. Relapses significantly increased hazard events; following a year (versus without relapses), by 31-48% (all P < 0.001). Pre-existing older age risk factors for incomplete recovery. For placebo-treated minimal (EDSS 1), it took 8.95 until limitation walking ability 4) 18.48 require assistance 6). Treating delayed these times 3.51 (95% confidence limit: 3.19, 3.96) 3.09 (2.60, 3.72), respectively. In relapsing-remitting those who worsened exclusively due events similar length EDSS values compared fastest superimposed relapses. Our confirm that contribute disability, primarily sclerosis. becomes dominant as evolves. are further The use delays accrual years, potential gain being highest earliest stages

Language: Английский

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Smouldering multiple sclerosis: the ‘real MS’

Therapeutic Advances in Neurological Disorders, Journal Year: 2022, Volume and Issue: 15

Published: Jan. 1, 2022

Using a philosophical approach or deductive reasoning, we challenge the dominant clinico-radiological worldview that defines multiple sclerosis (MS) as focal inflammatory disease of central nervous system (CNS). We provide range evidence to argue ‘real MS’ is in fact driven primarily by smouldering pathological process. In natural history studies and clinical trials, relapses activity revealed magnetic resonance imaging (MRI) MS patients on placebo disease-modifying therapies (DMTs) were found be poor predictors long-term evolution dissociated from disability outcomes. addition, progressive accumulation can occur independently relapse early course. This scenario underpinned more diffuse process may affect entire CNS. Many putative drivers potentially modified specific therapeutic strategies, an have major implications for management patients. hypothesise therapeutically targeting state ‘no evident activity’ (NEIDA) cannot sufficiently prevent MS, meaning treatment should also focus other brain spinal cord processes contributing slow loss neurological function. complemented with holistic systemic been shown worsen

Language: Английский

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Secondary Progressive Multiple Sclerosis

Neurology, Journal Year: 2021, Volume and Issue: 97(8), P. 378 - 388

Published: June 4, 2021

In most cases, multiple sclerosis (MS) begins with a relapsing-remitting course followed by insidious disability worsening that is independent from clinically apparent relapses and termed secondary progressive MS (SMPS). Major differences exist between (RRMS) SPMS, especially regarding therapeutic response to treatment. This review provides an overview of the pathology, differentiation, challenges in diagnosis treatment SPMS. We emphasize criticality conversion disease not only because such evidence progression, but also because, until recently, treatments effectively reduced progression relapsing were proven be effective Clear clinical, imaging, immunologic, or pathologic criteria marking transition RRMS SPMS have yet been established. Early identification will require tools that, together use appropriate treatments, may result better long-term outcomes for population patients

Language: Английский

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The potential of serum neurofilament as biomarker for multiple sclerosis

Brain, Journal Year: 2021, Volume and Issue: 144(10), P. 2954 - 2963

Published: June 26, 2021

Abstract Multiple sclerosis is a highly heterogeneous disease, and the detection of neuroaxonal damage as well its quantification critical step for patients. Blood-based serum neurofilament light chain (sNfL) currently under close investigation an easily accessible biomarker prognosis treatment response in patients with multiple sclerosis. There abundant evidence that sNfL levels reflect ongoing inflammatory-driven (e.g. relapses or MRI disease activity) predict activity over next few years. In contrast, association long-term clinical outcomes ability to slow, diffuse neurodegenerative less clear. However, early results from real-world cohorts trials using marker are encouraging. Importantly, algorithms should now be developed incorporate routine use guide individualized decision-making people sclerosis, together additional fluid biomarkers measures. Here, we propose specific scenarios where implementing measures may utility, including, among others: initial diagnosis, first choice, surveillance subclinical guidance therapy selection.

Language: Английский

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Multiple Sclerosis Therapy Consensus Group (MSTCG): position statement on disease-modifying therapies for multiple sclerosis (white paper)

Therapeutic Advances in Neurological Disorders, Journal Year: 2021, Volume and Issue: 14

Published: Jan. 1, 2021

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval various disease-modifying therapies our increased understanding mechanisms evolution in recent years have significantly changed prognosis course disease. This update Sclerosis Therapy Consensus Group treatment recommendation focuses on most important recommendations for multiple 2021. Our are based current scientific evidence apply to those medications approved wide parts Europe, particularly German-speaking countries (Germany, Austria, Switzerland).

Language: Английский

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Association of Early Progression Independent of Relapse Activity With Long-term Disability After a First Demyelinating Event in Multiple Sclerosis

JAMA Neurology, Journal Year: 2022, Volume and Issue: 80(2), P. 151 - 151

Published: Dec. 19, 2022

Progression independent of relapse activity (PIRA) is the main event responsible for irreversible disability accumulation in relapsing multiple sclerosis (MS).To investigate clinical and neuroimaging predictors PIRA at time first demyelinating attack factors associated with long-term outcomes people who present PIRA.This cohort study, conducted from January 1, 1994, to July 31, 2021, included patients a sclerosis; were recruited 1 study center Spain. Patients excluded if they refused participate, had alternative diagnoses, did not meet protocol requirements, inconsistent demographic information, or less than 3 assessments.Exposures (1) features (2) presenting PIRA, ie, confirmed (CDA) free-relapse period any after symptom onset, within (vs after) 5 years disease (ie, early/late PIRA), presence absence) new T2 lesions previous 2 active/nonactive PIRA).Expanded Disability Status Scale (EDSS) yearly increase rates since adjusted hazard ratios (HRs) EDSS 6.0.Of 1128 (mean [SD] age, 32.1 [8.3] years; 781 female individuals [69.2%]) 277 (25%) developed more events median (IQR) follow-up 7.2 (4.6-12.4) (for PIRA). Of all 86 (31%) early 73 144 (51%) active PIRA. slightly older, brain lesions, likely have oligoclonal bands those without Older age was only predictor (HR, 1.43; 95% CI, 1.23-1.65; P < .001 each older decade). steeper (0.18; 0.16-0.20 vs 0.04; 0.02-0.05; .001) an 8-fold greater risk reaching 6.0 7.93; 2.25-27.96; = Early late (0.31; 0.26-0.35 0.13; 0.10-0.16; 26-fold 26.21; 2.26-303.95; .009).Results this suggest that sclerosis, uncommon suggests unfavorable prognosis, especially it occurs course.

Language: Английский

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Multiple sclerosis: Neuroimmune crosstalk and therapeutic targeting

Cell, Journal Year: 2023, Volume and Issue: 186(7), P. 1309 - 1327

Published: March 1, 2023

Language: Английский

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Serum GFAP and NfL Levels Differentiate Subsequent Progression and Disease Activity in Patients With Progressive Multiple Sclerosis

Neurology Neuroimmunology & Neuroinflammation, Journal Year: 2022, Volume and Issue: 10(1)

Published: Nov. 14, 2022

Neurodegeneration and astrocytic activation are pathologic hallmarks of progressive multiple sclerosis (MS) can be quantified by serum neurofilament light chain (sNfL) glial fibrillary acidic protein (sGFAP). We investigated sNfL sGFAP as tools for stratifying patients with MS based on progression disease activity status.We leveraged our Comprehensive Longitudinal Investigation at the Brigham Women's Hospital (CLIMB) natural history study, which includes clinical, MRI data samples collected over more than 20 years. included a confirmed Expanded Disability Status Scale (EDSS) score ≥3 that corresponds classifier high risk underlying pathology. analyzed within 6 months from EDSS corresponding baseline visit. Patients who further developed 6-month disability (6mCDP) were classified progressors. stratified into active/nonactive new brain/spinal cord lesions or relapses in 2 years before during follow-up. Statistical analysis log-transformed sGFAP/sNfL assessed association demographic, features associations future disability.We 257 had an average 4.0 median follow-up after 7.6 was higher (adjusted β = 1.21; 95% CI 1.04-1.42; p 0.016), first 1.17; 1.01-1.36; 0.042). not increased presence activity. Higher levels, but associated 6mCDP hazard ratio [HR] 1.71; 1.19-2.45; 0.004). The stronger low HR 2.44; 1.32-4.52; 0.005) nonactive prior sample.Higher levels correlated subsequent progression, particularly patients, whereas reflected acute Thus, may used to stratify clinical research studies trials inform care.

Language: Английский

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