ArticleBMJ neurology open2022
Chronic lesion activity and disability progression in secondary progressive multiple sclerosis.
Article in BMJ neurology open, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01416181 (A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy of Natalizumab on Reducing Disability Progression in Subjects With Secondary Progressive Multiple Sclerosis, With Optional Open-Label Extension), which is not on this map. Cited by 33 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy of Natalizumab on Reducing Disability Progression in Subjects With Secondary Progressive Multiple Sclerosis, With Optional Open-Label Extension
Who cites it
33 citing papers in PubMed, 4 syntheses or guidelines pooled it, 39 citations in OpenAlex.
- Prevalence of Slowly Expanding Lesions in Patients With Multiple Sclerosis: A Systematic Review and Meta-Analysis.Neurology · 2026Pooled it
- Natalizumab for multiple sclerosis.The Cochrane database of systematic reviews · 2025Pooled it
- Associations between chronic active lesions and clinical outcomes in multiple sclerosis: A systematic literature review.Journal of managed care & specialty pharmacy · 2025Pooled it
- Neuroimaging markers and disability scales in multiple sclerosis: A systematic review and meta-analysis.PloS one · 2024Pooled it
- Effect of Evobrutinib on Slowly Expanding Lesion Volume in Relapsing Multiple Sclerosis: A Post Hoc Analysis of a Phase 2 Trial.Neurology · 2024Trial
- Ibudilast reduces slowly enlarging lesions in progressive multiple sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2024Trial
- Treatment Effects on Chronic Active Lesions in Multiple Sclerosis: Current Evidence and Future Perspectives.Neurology and therapy · 2026Review
- The hypoxia-inflammation cycle as a key mechanism of smoldering inflammation and progression in multiple sclerosis.Acta neuropathologica · 2026Review
- Diffusivity anisotropy signature of slowly expanding lesions predicts progression independent of relapse activity in multiple sclerosis.Journal of neurology, neurosurgery, and psychiatry · 2026Observational
- Slowly Expanding Lesions in Multiple Sclerosis: A Systematic Review and Meta-Analysis.NeuroSci · 2026Review
- Quantitative susceptibility mapping of paramagnetic rim lesions in early multiple sclerosis: A cross-sectional study of brain age and disability.Neuroimage. Reports · 2025Article
- Evolution of Chronic Lesion Tissue in Relapsing-Remitting Patients With Multiple Sclerosis: An Association With Disease Progression.Neurology(R) neuroimmunology & neuroinflammation · 2025Article
- Hypoxic Neuroinflammation in the Pathogenesis of Multiple Sclerosis.Brain sciences · 2025Review
- Article
- Current challenges in secondary progressive multiple sclerosis: diagnosis, activity detection and treatment.Frontiers in immunology · 2025Review
- Assessing disease progression and treatment response in progressive multiple sclerosis.Nature reviews. Neurology · 2024Review
- Imaging chronic active lesions in multiple sclerosis: a consensus statement.Brain : a journal of neurology · 2024Review
- Current and future role of MRI in the diagnosis and prognosis of multiple sclerosis.The Lancet regional health. Europe · 2024Review
- New Imaging Markers in Multiple Sclerosis and Related Disorders: Smoldering Inflammation and the Central Vein Sign.Neuroimaging clinics of North America · 2024Review
- The neuropathobiology of multiple sclerosis.Nature reviews. Neuroscience · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Objective: Slowly expanding lesions (SELs), a subgroup of chronic white matter lesions that gradually expand over time, have been shown to predict disability accumulation in primary progressive multiple sclerosis (MS) disease. However, the relationships between SELs, acute lesion activity (ALA), overall chronic lesion activity (CLA) and disability progression are not well understood. In this study, we examined the ASCEND phase III clinical trial, which compared natalizumab with placebo in secondary progressive MS (SPMS). Methods: Patients with complete imaging datasets between baseline and week 108 (N=600) were analysed for SEL prevalence (the number and volume of SELs), disability progression, ALA (assessed by gadolinium-enhancing lesions and new T2-hyperintense lesions) and CLA (assessed by T1-hypointense lesion volume increase within baseline T2-non-enhancing lesions identified as SELs and non-SELs). Results: CLA in both SELs and non-SELs was greater in patients with SPMS with confirmed disability progression than in those with no progression. In the complete absence of ALA at baseline and on study, SEL prevalence was significantly lower, while CLA within non-SELs remained associated with disability progression. Natalizumab decreased SEL prevalence and CLA in SELs and non-SELs compared with placebo. Conclusions: This study shows that CLA in patients with SPMS is decreased but persists in the absence of ALA and is associated with disability progression, highlighting the need for therapeutics targeting all mechanisms of CLA, including smouldering inflammation and neurodegeneration. Trial registration number: NCT01416181.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.