Trial reportNeurology(R) neuroimmunology & neuroinflammation2021
Safety and Immune Effects of Blocking CD40 Ligand in Multiple Sclerosis.
Trial report in Neurology(R) neuroimmunology & neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- In or out of control: Modulating regulatory T cell homeostasis and function with immune checkpoint pathways.Frontiers in immunology · 2022Pooled it
- First-in-Human, Phase 1, Randomized, Double-Blind, Placebo-Controlled Study of TNX-1500, an Fc-Modified anti-CD154 Monoclonal Antibody, Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-Ascending Doses in Healthy Adults.Journal of clinical immunology · 2026Trial
- Challenges and Innovation for Diagnosing and Treatment of Secondary Progressive Multiple Sclerosis.International journal of molecular sciences · 2026Review
- Immunoinformatics study of CD40 ligand-targeting vaccine constructs: a novel immunotherapeutic approach.Osong public health and research perspectives · 2025Article
- Mendelian randomization identifies proteins involved in neurodegenerative diseases.Brain : a journal of neurology · 2025Article
- Therapeutic advances in multiple sclerosis: Novel therapies (immune checkpoint inhibitors, CAR-T, Anti-CD40L).Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Update on novel multiple sclerosis treatments: from dismal defeat to scintillating success.Current opinion in neurology · 2025Review
- Exploring the Causal Association Between 91 Circulating Inflammatory Proteins and Neurodegenerative Diseases: A Bidirectional Two-Sample Mendelian Randomization and Bioinformatics Analysis.Brain and behavior · 2025Article
- New Frontiers in Multiple Sclerosis Treatment: From Targeting Costimulatory Molecules to Bispecific Antibodies.International journal of molecular sciences · 2025Review
- Frexalimab (SAR441344) as a potential multiautoimmune disorder tackling mAB targeting the CD40-CD40L pathway undergoing clinical trials: a review.Annals of medicine and surgery (2012) · 2024Review
- Slow Subcutaneous Release of Glatiramer Acetate or CD40-Targeting Peptide KGYYNeurology international · 2024Article
- Article
- Identification of crucial inflammaging related risk factors in multiple sclerosis.Frontiers in molecular neuroscience · 2024Article
- Single-Cell Sequencing Combined with Transcriptome Sequencing Constructs a Predictive Model of Key Genes in Multiple Sclerosis and Explores Molecular Mechanisms Related to Cellular Communication.Journal of inflammation research · 2024Article
- Advances in immune checkpoint-based immunotherapies for multiple sclerosis: rationale and practice.Cell communication and signaling : CCS · 2023Review
- Endurance Exercise Attenuates Established Progressive Experimental Autoimmune Encephalomyelitis and Is Associated with an Amelioration of Innate Immune Responses in NOD Mice.International journal of molecular sciences · 2023Article
- A gene regulatory network approach harmonizes genetic and epigenetic signals and reveals repurposable drug candidates for multiple sclerosis.Human molecular genetics · 2023Article
- Potential therapeutic targets of macrophages in inhibiting immune damage and fibrotic processes in musculoskeletal diseases.Frontiers in immunology · 2023Review
- Immune profiling in multiple sclerosis: a single-center study of 65 cytokines, chemokines, and related molecules in cerebrospinal fluid and serum.Frontiers in immunology · 2023Article
- Current and Future Biomarkers in Multiple Sclerosis.International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND AND
objectivesCostimulation by CD40 and its ligand CD40L (CD154) is important for the functional differentiation of T cells. Preclinical studies have recognized the importance of this costimulatory interaction in the pathogenesis of experimental models of multiple sclerosis (MS). To determine safety, pharmacokinetics, and immune effect of a humanized monoclonal antibody (mAb) against CD40 ligand (toralizumab/IDEC-131) in patients with relapsing-remitting MS (RRMS).
methodsThis single-institution open-label dose-escalation study (phase I) enrolled 12 patients with RRMS to receive 4 doses of 1, 5, 10, or 15 mg/kg of humanized αCD40L (toralizumab) IV infusion every other week. Patients were followed up to 18 weeks, annually, and finally at 5 years. In addition to safety and pharmacokinetics, other secondary and exploratory measurements are immune effects, clinical, MRI, laboratory, and neuropsychological evaluations.
resultsFifteen adverse events, all of mild to moderate severity, were considered to be of possible or of unknown relationship to treatment. No serious adverse events, including thromboembolic events, occurred during the 18-week defined study period. Annual and long-term follow-up at 5 years revealed no delayed toxicity. Pharmacokinetics were nonlinear between the 5 and 10 mg/kg dose groups. The serum half-life of toralizumab was consistent between the dose groups with a mean of 15.3 days (SD = 1.9). Flow cytometry revealed no depletion of lymphocyte subsets. An increase in the CD25+/CD3+ and CD25+/CD4+ ratio and a shift toward an anti-inflammatory cytokine response were seen after treatment. DISCUSSION: Our study suggests that blocking CD40L is safe and well tolerated in patients with RRMS while increasing CD25 CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence on the safety, pharmacokinetics, and immune effects of an mAb to CD40L in patients with RRMS.
Indexed as
Identifiers
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.