ArticleJournal of Crohn's & colitis2018
Effect of PF-00547659 on Central Nervous System Immune Surveillance and Circulating β7+ T Cells in Crohn's Disease: Report of the TOSCA Study.
Article in Journal of Crohn's & colitis, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Efficacy and Safety of the Anti-mucosal Addressin Cell Adhesion Molecule-1 Antibody Ontamalimab in Patients with Moderate-to-Severe Ulcerative Colitis or Crohn's Disease.Journal of Crohn's & colitis · 2024Trial
- Long-Term Safety and Efficacy of the Anti-Mucosal Addressin Cell Adhesion Molecule-1 Monoclonal Antibody Ontamalimab (SHP647) for the Treatment of Crohn's Disease: The OPERA II Study.Inflammatory bowel diseases · 2022Trial
- Long-term Safety and Efficacy of the Anti-MAdCAM-1 Monoclonal Antibody Ontamalimab [SHP647] for the Treatment of Ulcerative Colitis: The Open-label Study TURANDOT II.Journal of Crohn's & colitis · 2021Trial
- Trial
- Long-Term Safety of Ontamalimab in Patients with Moderate to Severe Inflammatory Bowel Disease.Clinical and experimental gastroenterology · 2026Article
- Human MAdCAM-1 antibodies as targeted immune modulators.Scientific reports · 2025Article
- Gut-directed therapeutics in inflammatory bowel disease.Current opinion in gastroenterology · 2025Review
- [Old and New Biologics and Small Molecules in Inflammatory Bowel Disease: Anti Integrins].The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi · 2024Review
- Choroid plexus volumetrics and brain inflammation in multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Anti-Integrins for the Treatment of Inflammatory Bowel Disease: Current Evidence and Perspectives.Clinical and experimental gastroenterology · 2021Review
- Targeting Immune Cell Trafficking - Insights From Research Models and Implications for Future IBD Therapy.Frontiers in immunology · 2021Review
- The protective role of the miR-25-mediated notch signaling pathway in the memory capacity and brain tissue of mice with central nervous system infections.American journal of translational research · 2021Article
- Population Pharmacokinetics and Pharmacodynamics of Ontamalimab (SHP647), a Fully Human Monoclonal Antibody Against Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1), in Patients With Ulcerative Colitis or Crohn's Disease.Journal of clinical pharmacology · 2020Article
- The role of integrins in the pathogenesis of inflammatory bowel disease: Approved and investigational anti-integrin therapies.Medicinal research reviews · 2020Review
Corrections and comments
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Authors and funding
23 authors at 10 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsProgressive multifocal leukoencephalopathy [PML], a brain infection associated with anti-integrin drugs that inhibit lymphocyte translocation from bloodstream to tissue, can be fatal. Decreased central nervous system [CNS] immune surveillance leading to this infection has been reported in patients with multiple sclerosis or Crohn's disease treated with anti-integrin antibody natalizumab. PF-00547659 is an investigational human monoclonal antibody for inflammatory bowel disease, targeted against α4β7-mucosal addressin cell-adhesion molecule-1 [the integrin ligand selectively expressed in the gut]. We hypothesised that this selective agent would not affect central nervous system immune surveillance.
methodsCerebrospinal fluid from five healthy volunteers, and from 10 patients with Crohn's disease previously treated with immunosuppressants, was evaluated to assess the feasibility of the study. Subsequently, 39 patients with active Crohn's disease and previous immunosuppression were evaluated over 12 weeks of PF-00547659-induction therapy. We measured total lymphocytes, T cell subsets in cerebrospinal fluid, and circulating β7+ memory cells. Disease activity was assessed using the Harvey-Bradshaw Index.
resultsPatients treated with PF-00547659 had no reduction of cerebrospinal fluid lymphocytes, T-lymphocyte subsets, or CD4:CD8 ratio, whereas circulating β7+ memory cells increased significantly. A total of 28/35 [80%] patients had a clinical response and 27/34 [79%] had disease remission. Treatment-related adverse events, none serious, were reported in 23/49 [47%] patients.
conclusionsIn patients with active Crohn's disease, natalizumab therapy increases the risk for PML, and the increased risk is thought to be associated with iatrogenic leukopenia within the CNS. PML under PF-00547659 may be a lesser concern, as this agent did not reduce lymphocytes or T cell subsets in the cerebrospinal fluid.
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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.