ArticleMultiple sclerosis (Houndmills, Basingstoke, England)2016
Inclusion of brain volume loss in a revised measure of 'no evidence of disease activity' (NEDA-4) in relapsing-remitting multiple sclerosis.
Article in Multiple sclerosis (Houndmills, Basingstoke, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04153773 (Retinal Thickness as a Potential Biomarker of Neurodegeneration and Early Cognitive Impairment in Patients With Multiple Sclerosis), which is not on this map. Cited by 131 papers, 3 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.
Retinal Thickness as a Potential Biomarker of Neurodegeneration and Early Cognitive Impairment in Patients With Multiple Sclerosis
Who cites it
131 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Expert Panel Consensus Guidelines of the German Society of Neuroradiology on the Use of Magnetic Resonance Imaging in the Diagnosis and Monitoring of Multiple Sclerosis.Clinical neuroradiology · 2026Guideline
- Association of NEDA-4 With No Long-term Disability Progression in Multiple Sclerosis and Comparison With NEDA-3: A Systematic Review and Meta-analysis.Neurology(R) neuroimmunology & neuroinflammation · 2022Pooled it
- Fingolimod for relapsing-remitting multiple sclerosis.The Cochrane database of systematic reviews · 2016Pooled it
- Long-term safety and efficacy of ponesimod in participants with relapsing multiple sclerosis: results from the phase 3 OPTIMUM 5-year long term extension study.Journal of neurology · 2026Trial
- Glial Fibrillary Acidic Protein as a Marker of Disease in Relapsing Multiple Sclerosis: Post Hoc Analysis of Phase 3 Ozanimod Trials.European journal of neurology · 2025Trial
- Measuring treatment response to advance precision medicine for multiple sclerosis.Annals of clinical and translational neurology · 2021Trial
- Ponesimod Compared With Teriflunomide in Patients With Relapsing Multiple Sclerosis in the Active-Comparator Phase 3 OPTIMUM Study: A Randomized Clinical Trial.JAMA neurology · 2021Trial
- Effect of delayed-release dimethyl fumarate on no evidence of disease activity in relapsing-remitting multiple sclerosis: integrated analysis of the phase III DEFINE and CONFIRM studies.European journal of neurology · 2017Trial
- The Evaluation of Oxidative Stress Parameters in Serum Patients with Relapsing-Remitting Multiple Sclerosis Treated with II-Line Immunomodulatory Therapy.Oxidative medicine and cellular longevity · 2017Trial
- Integration of retinal layer thinning into NEDA-3 predicts disability progression in multiple sclerosis.Journal of neurology · 2026Observational
- Mitigating the Impact of MR Sequence Parameters: Increasing the Robustness of DL-Based Cortical Thickness Estimates.Human brain mapping · 2026Article
- Ocrelizumab in early relapsing-remitting multiple sclerosis: first interim analysis of the MUSPO Italian prospective cohort.Journal of neurology · 2026Observational
- Cognitive function is associated with risk of conversion to secondary progressive multiple sclerosis: A cross-sectional study.PloS one · 2026Article
- High-Dose Pulse Glucocorticoid Treatment Prevents White Matter Spinal Cord Pseudoatrophy in Newly Diagnosed Multiple Sclerosis.Annals of neurology · 2025Article
- Refining Prognostic Factors in Adult-Onset Multiple Sclerosis: A Narrative Review of Current Insights.International journal of molecular sciences · 2025Review
- Pediatric multiple sclerosis: Improving outcome through high-efficacy therapies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Optimizing Drug Selection in Children with Multiple Sclerosis: What Do We Know and What Remains Unanswered?Paediatric drugs · 2025Review
- Patients with relapsing-remitting multiple sclerosis show accelerated whole brain volume and thalamic volume loss early in disease.Neuroradiology · 2025Article
- Measuring Disease Progression in Multiple Sclerosis Clinical Drug Trials and Impact on Future Patient Care.CNS drugs · 2025Review
- Deep learning-driven MRI for accurate brain volumetry in murine models of neurodegenerative diseases.Frontiers in neuroscience · 2025Article
71 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background'No evidence of disease activity' (NEDA), defined as absence of magnetic resonance imaging activity (T2 and/or gadolinium-enhanced T1 lesions), relapses and disability progression ('NEDA-3'), is used as a comprehensive measure of treatment response in relapsing multiple sclerosis (RMS), but is weighted towards inflammatory activity. Accelerated brain volume loss (BVL) occurs in RMS and is an objective measure of disease worsening and progression.
objectiveTo assess the contribution of individual components of NEDA-3 and the impact of adding BVL to NEDA-3 ('NEDA-4')
methodsWe analysed data pooled from two placebo-controlled phase 3 fingolimod trials in RMS and assessed NEDA-4 using different annual BVL mean rate thresholds (0.2%-1.2%).
resultsAt 2 years, 31.0% (217/700) of patients receiving fingolimod 0.5 mg achieved NEDA-3 versus 9.9% (71/715) on placebo (odds ratio (OR) 4.07; p < 0.0001). Adding BVL (threshold of 0.4%), the respective proportions of patients achieving NEDA-4 were 19.7% (139/706) and 5.3% (38/721; OR 4.41; p < 0.0001). NEDA-4 status favoured fingolimod across all BVL thresholds tested (OR 4.01-4.41; p < 0.0001).
conclusionNEDA-4 has the potential to capture the impact of therapies on both inflammation and neurodegeneration, and deserves further evaluation across different compounds and in long-term studies.
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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.