Trial reportJournal of neurology, neurosurgery, and psychiatry2014
Oral ponesimod in relapsing-remitting multiple sclerosis: a randomised phase II trial.
Trial report in Journal of neurology, neurosurgery, and psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 64 papers, 7 of them syntheses that pooled it.
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.
Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-finding Study to Evaluate the Efficacy, Safety, and Tolerability of Three Doses of ACT-128800, an Oral S1P1 Receptor Agonist, Administered for Twenty-four Weeks in Patients With Relapsing-remitting Multiple Sclerosis
A Phase I/II Dose Escalation/Adaptive Design Study to Evaluate the Safety and Efficacy of IMCY-0141 in Patients With Relapsing Remitting-Multiple Sclerosis (RR-MS)
Who cites it
64 citing papers in PubMed, 7 syntheses or guidelines pooled it, 149 citations in OpenAlex.
- Natalizumab and Tyruko (natalizumab biosimilar) for treating highly active relapsing-remitting multiple sclerosis after at least one disease-modifying therapy: a systematic review and economic model.Health technology assessment (Winchester, England) · 2026Pooled it
- Efficacy and safety of disease-modifying oral drugs in treatment of relapsing-remitting multiple sclerosis: systematic review and network meta-analysis.Frontiers in immunology · 2026Pooled it
- The Comparative Effectiveness and Tolerability of Sphingosine-1-Phosphate Receptor Modulators in Patients With Multiple Sclerosis: A Network Meta-Analysis of Randomized Controlled Trials.Annals of clinical and translational neurology · 2025Pooled it
- Brain volume loss in relapsing multiple sclerosis: indirect treatment comparisons of available disease-modifying therapies.BMC neurology · 2024Pooled it
- Safety of S1P Modulators in Patients with Immune-Mediated Diseases: A Systematic Review and Meta-Analysis.Drug safety · 2021Pooled it
- Efficacy and acceptability of the S1P receptor in the treatment of multiple sclerosis: a meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Pooled it
- Impact of Demographics, Organ Impairment, Disease, Formulation, and Food on the Pharmacokinetics of the Selective S1PClinical pharmacokinetics · 2017Pooled it
- Safety, pharmacokinetics and pharmacodynamics of NXC736, a novel sphingosine-1-phosphate receptor modulator.British journal of clinical pharmacology · 2026Trial
- 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
- An exposure-response analysis of ponesimod clinical efficacy in a randomized phase III study in patients with relapsing multiple sclerosis.CPT: pharmacometrics & systems pharmacology · 2022Trial
- Single-dose of LC51-0255, a selective S1PClinical and translational science · 2022Trial
- An Exposure-Response Analysis of the Clinical Efficacy of Ponesimod in a Randomized Phase II Study in Patients with Multiple Sclerosis.Clinical pharmacokinetics · 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
- Efficacy and safety of ozanimod in multiple sclerosis: Dose-blinded extension of a randomized phase II study.Multiple sclerosis (Houndmills, Basingstoke, England) · 2019Trial
- Cardiac Safety of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator: Results of a Thorough QT/QTc Study.Clinical pharmacology in drug development · 2018Trial
- Pharmacokinetics, Pharmacodynamics, Tolerability, and Food Effect of Cenerimod, a Selective S1P₁ Receptor Modulator in Healthy Subjects.International journal of molecular sciences · 2017Trial
- Absolute Bioavailability of Ponesimod, a Selective S1PEuropean journal of drug metabolism and pharmacokinetics · 2017Trial
- Effects of multiple-dose ponesimod, a selective S1PDrug design, development and therapy · 2017Trial
- Biocomparison of Three Formulations of the S1P1 Receptor Modulator Ponesimod in Healthy Subjects.Drugs in R&D · 2015Trial
- GPCR drug discovery: new agents, targets and indications.Nature reviews. Drug discovery · 2025Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
11 authors at 7 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThis double-blind, placebo-controlled, dose-finding phase IIb study evaluated the efficacy and safety of ponesimod, an oral selective S1P1 receptor modulator, for the treatment of patients with relapsing-remitting multiple sclerosis (RRMS).
methods464 patients were randomised to receive once-daily oral ponesimod 10, 20 or 40 mg, or placebo for 24 weeks. The primary endpoint was the cumulative number of new T1 gadolinium-enhanced (T1 Gd+) lesions per patient recorded every 4 weeks from weeks 12 to 24 after study drug initiation. Secondary endpoints were the annualised confirmed relapse rate (ARR) and time to first confirmed relapse. Safety and tolerability were also evaluated.
resultsThe mean cumulative number of new T1 Gd+ lesions at weeks 12-24 was significantly lower in the ponesimod 10 mg (3.5; rate ratio (RR) 0.57; p=0.0318), 20 mg (1.1; RR 0.17; p<0.0001) and 40 mg (1.4; RR 0.23; p<0.0001) groups compared with placebo (6.2). The mean ARR was lower with 40 mg ponesimod versus placebo, with a maximum reduction of 52% (0.25 vs 0.53; p=0.0363). The time to first confirmed relapse was increased with ponesimod compared with placebo. The proportion of patients with ≥ 1 treatment-emergent adverse events (AEs) was similar across ponesimod groups and the placebo group. Frequently reported AEs with higher incidence in the three ponesimod groups compared with placebo were anxiety, dizziness, dyspnoea, increased alanine aminotransferase, influenza, insomnia and peripheral oedema.
conclusionsOnce-daily treatment with ponesimod 10, 20 or 40 mg significantly reduced the number of new T1 Gd+ lesions and showed a beneficial effect on clinical endpoints. Ponesimod was generally well tolerated, and further investigation of ponesimod for the treatment of RRMS is under consideration. TRIAL REGISTRATION NUMBER: NCT01006265.
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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.