ArticleJournal of clinical pharmacology2021
Modeling the Efficacy of Natalizumab in Multiple Sclerosis Patients Who Switch From Every-4-Week Dosing to Extended-Interval Dosing.
Article in Journal of clinical pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Efficacy and safety of extended-interval dosing of natalizumab in multiple sclerosis: a systematic review and meta-analysis with subgroup evaluation.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Pooled it
- Pharmacokinetics and Pharmacodynamics of Natalizumab 6-Week Dosing vs Continued 4-Week Dosing for Relapsing-Remitting Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2024Trial
- Selective IgM Hypogammaglobulinemia and Multiple Sclerosis Treated with Natalizumab and Ofatumumab: A Case Report.Journal of personalized medicine · 2025Article
- MS treatment de-escalation: review and commentary.Journal of neurology · 2024Review
- Disease activity and neonatal outcomes after exposure to natalizumab throughout pregnancy.Journal of neurology, neurosurgery, and psychiatry · 2024Observational
- High levels of endothelial ICAM-1 prohibit natalizumab mediated abrogation of CD4Journal of neuroinflammation · 2023Article
- An Elusive Target: Inhibitors of JC Polyomavirus Infection and Their Development as Therapeutics for the Treatment of Progressive Multifocal Leukoencephalopathy.International journal of molecular sciences · 2023Review
- Real-World Effectiveness of Natalizumab Extended Interval Dosing in a French Cohort.Neurology and therapy · 2023Article
- Monoclonal Antibodies in the Treatment of Relapsing Multiple Sclerosis: an Overview with Emphasis on Pregnancy, Vaccination, and Risk Management.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Natalizumab extended-interval dosing in multiple sclerosis to mitigate progressive multifocal leukoencephalopathy risk: initial study evidence and real-world experience.Journal of central nervous system disease · 2022Review
- Teriflunomide Inhibits JCPyV Infection and Spread in Glial Cells and Choroid Plexus Epithelial Cells.International journal of molecular sciences · 2021Article
- Potential Risks and Benefits of Multiple Sclerosis Immune Therapies in the COVID-19 Era: Clinical and Immunological Perspectives.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- No evidence for loss of natalizumab effectiveness with every-6-week dosing: a propensity score-matched comparison with every-4-week dosing in patients enrolled in the Tysabri Observational Program (TOP).Therapeutic advances in neurological disorders · 2021Article
- T lymphopenia in multiple sclerosis patients treated with ofatumumab: Even with consideration for CD3Multiple sclerosis journal - experimental, translational and clinicalArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natalizumab is approved for multiple sclerosis treatment at a dose of 300 mg every 4 weeks. Extended-interval dosing of natalizumab has been proposed as a strategy to mitigate the risk of progressive multifocal leukoencephalopathy, but the efficacy of extended-interval dosing is not established. Previous models suggesting lower efficacy when initiating natalizumab treatment with extended-interval dosing rather than every-4-week dosing are inconsistent with reports from clinical observations and real-world studies conducted in patient populations switching to extended-interval dosing after a period of receiving natalizumab every 4 weeks. Here, the efficacy of natalizumab extended-interval dosing was modeled specifically in patients switching from every-4-week dosing to extended-interval dosing. Published population pharmacokinetic/pharmacodynamic models were used to simulate the distribution of alpha-4 integrin saturations for different body weight categories and dosing intervals (every 5, 6, 7, 8, 10, or 12 weeks). Generalized estimating equations relating alpha-4 integrin saturation to probability of multiple sclerosis lesion or relapse were derived from RESTORE trial data, which included patients (n = 175) who discontinued natalizumab after being treated every 4 weeks for ≥1 year and had no relapses in the year before discontinuation. The model-based simulations described indicate that every-5-week or every-6-week dosing is likely to maintain the efficacy of natalizumab, particularly at body weights <80 kg, in patients who switch after a period of stability on every-4-week dosing. The efficacy of natalizumab decreases as dosing intervals and body weight increase. Partial model validation was achieved in that observed outcomes in an independent clinical study were similar to those predicted by the models.
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