Towards a biological view of multiple sclerosis from early subtle to clinical progression: an expert opinion

Journal of Neurology, Journal Year: 2025, Volume and Issue: 272(2)

Published: Feb. 1, 2025

Language: Английский

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Tolebrutinib in Nonrelapsing Secondary Progressive Multiple Sclerosis

New England Journal of Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Throughout the course of multiple sclerosis, gradually progressive neurologic impairment can occur, which has been called disability accrual. Current disease-modifying therapies for sclerosis have limited effects on accrual unrelated to relapses, is thought be partially caused by chronic, nonresolving neuroinflammation within central nervous system. Tolebrutinib an oral, brain-penetrant Bruton's tyrosine kinase inhibitor that targets myeloid cells (including microglia) and B in both periphery There are no approved treatments nonrelapsing secondary sclerosis. In a phase 3, double-blind, placebo-controlled, event-driven trial, we randomly assigned participants with 2:1 ratio, receive tolebrutinib (60 mg once daily) or matching placebo. The primary end point was confirmed progression sustained at least 6 months, assessed time-to-event analysis. A total 1131 underwent randomization: 754 were 377 median follow-up 133 weeks. smaller percentage group than placebo had months (22.6% vs. 30.7%; hazard 0.69; 95% confidence interval, 0.55 0.88; P = 0.003). Serious adverse events occurred 15.0% 10.4% those group. 4.0% 1.6% increases alanine aminotransferase levels more 3 times upper limit normal range. risk lower among who received treatment (Funded Sanofi; HERCULES ClinicalTrials.gov number, NCT04411641.).

Language: Английский

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Tolebrutinib versus Teriflunomide in Relapsing Multiple Sclerosis

New England Journal of Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Tolebrutinib is an oral, brain-penetrant, and bioactive Bruton's tyrosine kinase inhibitor that modulates peripheral inflammation persistent immune activation within the central nervous system, including disease-associated microglia B cells. More data are needed on its efficacy safety in treating relapsing multiple sclerosis. In two phase 3, double-blind, double-dummy, event-driven trials (GEMINI 1 GEMINI 2), participants with sclerosis were randomly assigned a 1:1 ratio to receive tolebrutinib (60 mg once daily) or teriflunomide (14 daily), each matching placebo. The primary end point was annualized relapse rate. key secondary confirmed worsening of disability sustained for at least 6 months, which assessed time-to-event analysis pooled across trials. A total 974 enrolled 1, 899 2. median follow-up 139 weeks. rate groups 0.13 0.12, respectively, (rate ratio, 1.06; 95% confidence interval [CI], 0.81 1.39; P = 0.67) 0.11 0.11, 2 1.00; CI, 0.75 1.32; 0.98). percentage months 8.3% 11.3% (hazard 0.71; 0.53 0.95; no formal hypothesis testing conducted owing prespecified hierarchical plan, width not adjusted testing). who had adverse events similar treatment groups, although minor bleeding higher group than (petechiae occurred 4.5% vs. 0.3%, heavy menses 2.6% 1.0%). superior decreasing rates among (Funded by Sanofi; ClinicalTrials.gov numbers, NCT04410978 NCT04410991, respectively.).

Language: Английский

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A Window into New Insights on Progression Independent of Relapse Activity in Multiple Sclerosis: Role of Therapies and Current Perspective

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 884 - 884

Published: Jan. 21, 2025

In multiple sclerosis (MS), there is significant evidence indicating that both progression independent of relapse activity (PIRA) and relapse-related worsening events contribute to the accumulation progressive disability from onset disease throughout its course. Understanding compartmentalized pathophysiology MS would enhance comprehension mechanisms, overcoming traditional distinction in phenotypes. Smoldering thought be maintained by a continuous interaction between parenchymal chronic processes neuroinflammation neurodegeneration intrathecal compartment. This review provides comprehensive up-to-date overview neuropathological immunological related mechanisms underlying PIRA phenomena MS, with focus on studies investigating impact currently available therapies these complex mechanisms.

Language: Английский

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A real-world data of serum neurofilament light chain in a large cohort of Egyptian multiple sclerosis patients: Hospital-based study

Multiple Sclerosis and Related Disorders, Journal Year: 2025, Volume and Issue: 94, P. 106286 - 106286

Published: Jan. 22, 2025

Language: Английский

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Quality of life is decreased in persons with relapsing-remitting multiple sclerosis experiencing progression independent of relapse activity

Multiple Sclerosis Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

Introduction: Reduced quality of life (QoL) is an early feature multiple sclerosis (MS). The effect progression independent relapse activity (PIRA) on QoL poorly investigated. Objective: To assess the impact PIRA using patient-reported outcome measures (PROMs). Methods: In a prospective observational study, 125 newly diagnosed persons with relapsing-remitting MS (PwRRMS) were assessed over 5 years with: EuroQoL-5-Dimension-3-level (EQ-5D-3L), EQ-visual-analogous-scale (EQ-VAS) and 29-item-MS-Impact-Scale (MSIS-29). PwRRMS dichotomized: (worsening expanded disability status scale (EDSS), timed-25-foot-walk or 9-hole-peg-test, relapses) versus non-PIRA. compared at baseline, year (y5) delta values (baseline scores subtracted from y5 scores) annually linear-mixed-effects-models. Results: At y5, 19.2% had PIRA. non-PIRA older ( p < 0.001). lower EQ-5D-3L = 0.001), higher MSIS-29-PHYS showed 0.001) EQ-VAS 0.010), 0.004) MSIS-29-PSYCH 0.036). Linear-mixed-effects-models that, to PIRA, improvement in QoL: EQ-5D-3L: β 0.039, 0.001; EQ-VAS: 2.401, MSIS-29-PHYS: −0.107, MSIS-29-PSYCH, −0.115, 0.001, during 5-year study period. Conclusion: Deteriorating course (RRMS) strongly associated Our results suggest that PROMs should be monitored recognized as important aspect progression.

Language: Английский

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From biomarkers to brain imaging: Refining early diagnosis of mild cognitive impairment

Journal of Clinical Neuroscience, Journal Year: 2025, Volume and Issue: unknown, P. 111187 - 111187

Published: March 1, 2025

Language: Английский

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Multiple sclerosis: advances and challenges in diagnosis

Current Opinion in Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Purpose of review This article explores the most recent developments in multiple sclerosis (MS), including a selection advances diagnostic neuroimaging markers. The proposed revision criteria, new concepts on prodromal period, and differential diagnosis MS are included as well. Recent findings Interesting changes have been introduced to recently 2024 revisions criteria. Optic nerve is 5 th CNS topography, additional advanced MRI markers included, well specific cases “radiologically isolated syndrome” considered at risk future relapses. power central vein sign, paramagnetic rim lesion, cortical lesions demonstrated lines research adult pediatric patients with MS. contribution lesions, slowly expanding choroid plexus enlargement, leptomeningeal enhancement, addition measurement brain spinal cord atrophy, expanded our understanding early disease progression. Summary highlights studies that significantly contributed increase accuracy both patients, potential improve detection

Language: Английский

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Morphological and functional assessment of the vagus nerve in multiple sclerosis

Clinical Autonomic Research, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

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Smouldering-associated worsening or SAW: the next therapeutic challenge in managing multiple sclerosis

Multiple Sclerosis and Related Disorders, Journal Year: 2024, Volume and Issue: 92, P. 106194 - 106194

Published: Nov. 27, 2024

Language: Английский

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