Trial reportJournal of neurology2022
Siponimod vs placebo in active secondary progressive multiple sclerosis: a post hoc analysis from the phase 3 EXPAND study.
Trial report in Journal of neurology, 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 13 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
13 citing papers in PubMed, 17 citations in OpenAlex.
- Modulation of the immunological and neuroinflammatory microenvironment in older people with multiple sclerosis.Frontiers in immunology · 2026Review
- Real-world siponimod use in secondary progressive multiple sclerosis: the RESYZE study.Therapeutic advances in neurological disorders · 2026Article
- Effectiveness of Siponimod with Up to 2 Years of Treatment in a Real-World Setting in People with SPMS: Analysis from the Novartis Global Managed Access Program.Degenerative neurological and neuromuscular disease · 2026Article
- Impact of whole-body vibration training on gait in patients with progressive multiple sclerosis: a pilot randomised study.BMJ neurology open · 2026Article
- A real-world retrospective study to assess the effectiveness and safety profile of siponimod in Chinese patients with relapsing forms of multiple sclerosis.BMC neurology · 2025Article
- Current landscape of innovative drug development and regulatory support in China.Signal transduction and targeted therapy · 2025Review
- Progressive multiple sclerosis: Evaluating current therapies and exploring future treatment strategies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Added value of spinal cord MRI in detecting active disease in non-relapsing progressive multiple sclerosis patients.Journal of neurology · 2025Article
- Targeting immune cell migration as therapy for inflammatory disease: a review.Frontiers in immunology · 2025Review
- Current challenges in secondary progressive multiple sclerosis: diagnosis, activity detection and treatment.Frontiers in immunology · 2025Review
- Treatment Patterns and Unmet Need for Patients with Progressive Multiple Sclerosis in the United States: Survey Results from 2016 to 2021.Neurology and therapy · 2023Article
- An update on the use of sphingosine 1-phosphate receptor modulators for the treatment of relapsing multiple sclerosis.Expert opinion on pharmacotherapy · 2023Review
- Disease-modifying therapies for relapsing/active secondary progressive multiple sclerosis - a review of population-specific evidence from randomized clinical trials.Therapeutic advances in neurological disorders · 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
17 authors at 11 institutions in 6 countries.
Funding
Abstract
backgroundSiponimod is a sphingosine 1-phosphate receptor modulator approved for active secondary progressive multiple sclerosis (aSPMS) in most countries; however, phase 3 EXPAND study data are from an SPMS population with/without disease activity. A need exists to characterize efficacy/safety of siponimod in aSPMS.
methodsPost hoc analysis of participants with aSPMS (≥ 1 relapse in 2 years before study and/or ≥ 1 T1 gadolinium-enhancing [Gd +] magnetic resonance imaging [MRI] lesions at baseline) receiving oral siponimod (2 mg/day) or placebo for up to 3 years in EXPAND. ENDPOINTS: 3-month/6-month confirmed disability progression (3mCDP/6mCDP); 3-month confirmed ≥ 20% worsening in Timed 25-Foot Walk (T25FW); 6-month confirmed improvement/worsening in Symbol Digit Modalities Test (SDMT) scores (≥ 4-point change); T2 lesion volume (T2LV) change from baseline; number of T1 Gd + lesions baseline-month 24; number of new/enlarging (N/E) T2 lesions over all visits.
resultsData from 779 participants with aSPMS were analysed. Siponimod reduced risk of 3mCDP/6mCDP vs placebo (by 31%/37%, respectively; p < 0.01); there was no significant effect on T25FW. Siponimod increased likelihood of 6-month confirmed SDMT improvement vs placebo (by 62%; p = 0.007) and reduced risk of 6-month confirmed SDMT worsening (by 27%; p = 0.060). Siponimod was associated with less increase in T2LV (1316.3 vs 13.3 mm
conclusionsIn aSPMS, siponimod reduced risk of disability progression and was associated with benefits on cognition and MRI outcomes vs placebo.
trial registrationClinicalTrials.gov number: NCT01665144.
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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.