Trial reportMultiple sclerosis (Houndmills, Basingstoke, England)2022
Effect of siponimod on magnetic resonance imaging measures of neurodegeneration and myelination in secondary progressive multiple sclerosis: Gray matter atrophy and magnetization transfer ratio analyses from the EXPAND phase 3 trial.
Trial report in Multiple sclerosis (Houndmills, Basingstoke, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01665144 (A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Variable Treatment Duration Study Evaluating the Efficacy and Safety of Siponimod), which is not on this map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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, Parallel-group, Placebo-controlled Variable Treatment Duration Study Evaluating the Efficacy and Safety of Siponimod (BAF312) in Patients With Secondary Progressive Multiple Sclerosis Followed by Extended Treatment With Open-label BAF312.
Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Progression to Wheelchair in Secondary Progressive Multiple Sclerosis and Impact of Siponimod: Post Hoc Analyses From the EXPAND Study.European journal of neurology · 2026Trial
- Effect of ibudilast on thalamic magnetization transfer ratio and volume in progressive multiple sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2023Trial
- From Demyelination to Intervention: Natural Compounds as Emerging Therapeutic Targets in Multiple Sclerosis Neuroinflammation.Journal of immunology research · 2026Review
- Bridging Inflammation and Neurodegeneration in Multiple Sclerosis: Mechanisms and Emerging Therapies.Cureus · 2026Review
- Effects of sphingosine-1-phosphate receptor modulators on remyelination in multiple sclerosis: evidence fromFrontiers in immunology · 2026Review
- Siponimod inhibits disease-associated microglia-T cell interactions in chronic experimental autoimmune encephalomyelitis.Acta neuropathologica communications · 2025Article
- Modulating Cerebrospinal Fluid Composition in Neurodegenerative Processes: Modern Drug Delivery and Clearance Strategies.International journal of molecular sciences · 2025Review
- The Role of MRI Lesions in Identifying Secondary Progressive Multiple Sclerosis: A Comprehensive Review.Journal of clinical medicine · 2025Review
- Identifying Biomarkers for Remyelination and Recovery in Multiple Sclerosis: A Measure of Progress.Biomedicines · 2025Review
- "Proteinjury": a universal pathological mechanism mediated by cerebrospinal fluid in neurodegeneration and trauma.Frontiers in cell and developmental biology · 2025Review
- Serum Glial Fibrillary Acidic Protein and Neurofilament Light Chain Levels Reflect Different Mechanisms of Disease Progression under B-Cell Depleting Treatment in Multiple Sclerosis.Annals of neurology · 2024Article
- Decoding Gray Matter Involvement in Multiple Sclerosis via Imaging.Neuroimaging clinics of North America · 2024Review
- Advanced MRI Techniques: Diagnosis and Follow-Up of Multiple Sclerosis.Diagnostics (Basel, Switzerland) · 2024Review
- Siponimod Attenuates Neuronal Cell Death Triggered by Neuroinflammation via NFκB and Mitochondrial Pathways.International journal of molecular sciences · 2024Article
- New views on the complex interplay between degeneration and autoimmunity in multiple sclerosis.Frontiers in cellular neuroscience · 2024Article
- High-frequency longitudinal white matter diffusion- and myelin-based MRI database: Reliability and variability.Human brain mapping · 2023Article
- Inflammation in multiple sclerosis: consequences for remyelination and disease progression.Nature reviews. Neurology · 2023Review
- An update on the use of sphingosine 1-phosphate receptor modulators for the treatment of relapsing multiple sclerosis.Expert opinion on pharmacotherapy · 2023Review
- Multiple sclerosis: 2023 update.Free neuropathology · 2023Article
- Bioavailable central nervous system disease-modifying therapies for multiple sclerosis.Frontiers in immunology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 10 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMagnetic resonance imaging (MRI) measurements of gray matter (GM) atrophy and magnetization transfer ratio (MTR; correlate of myelination) may provide better insights than conventional MRI regarding brain tissue integrity/myelination in multiple sclerosis (MS).
objectiveTo examine the effect of siponimod in the EXPAND trial on whole-brain and GM atrophy, newly formed normalized magnetization transfer ratio (nMTR) lesions, and nMTR-assessed integrity of normal-appearing brain tissue (NABT), cortical GM (cGM), and normal-appearing white matter (NAWM).
methodsPatients with secondary progressive multiple sclerosis (SPMS) received siponimod (2 mg/day;
resultsCompared with placebo, siponimod significantly reduced progression of whole-brain and GM atrophy over 12/24 months, and was associated with improvements in brain tissue integrity/myelination within newly formed nMTR lesions and across NABT, cGM, and NAWM over 24 months. Effects were consistent across age, disease duration, inflammatory activity subgroups, and disease severity.
conclusionSiponimod reduced brain tissue damage in patients with SPMS as evidenced by objective measures of brain tissue integrity/myelination. This is consistent with central nervous system (CNS) effects observed in preclinical models. ClinicalTrials.gov number: NCT01665144.
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What OpenQuestion holds
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.