Effect of PF-00547659 on Central Nervous System Immune Surveillance and Circulating beta 7+T Cells in Crohn's Disease: Report of the TOSCA Study
| العنوان: | Effect of PF-00547659 on Central Nervous System Immune Surveillance and Circulating beta 7+T Cells in Crohn's Disease: Report of the TOSCA Study |
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| المؤلفون: | Richard M. Ransohoff, Olaf Stüve, Harald Vogelsang, Sunday Rivers, Clare Robert A, Kenneth J. Gorelick, Fabio Cataldi, Mina Hassan-Zahraee, Pierre Desreumaux, Geert R. D'Haens, John B. Cheng, Annamarie Kaminski, Yanhua Zhang, Alaa Ahmad, William J. Sandborn, Vivek Pradhan, Severine Vermeire, Matthieu Allez, André Van Gossum, Daniel C. Baumgart, Matthew O Sikpi, Gail M. Comer, Walter Reinisch |
| المساهمون: | AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology |
| المصدر: | Journal of Crohn's and Colitis, 12 (2 Journal of Crohn's & Colitis Journal of Crohn s & colitis, 12(2), 188-196. Elsevier |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Adult, Central Nervous System, Male, Crohn’s disease, Integrin beta Chains, Adolescent, Lymphocyte, medicine.medical_treatment, T cell, T-Lymphocytes, Antibodies, Monoclonal, Humanized, Inflammatory bowel disease, 03 medical and health sciences, Young Adult, Natalizumab, Crohn Disease, T-Lymphocyte Subsets, inflammatory bowel disease, medicine, Humans, Gastro-entérologie, MAdCAM-1, Lymphocyte Count, Immunologic Surveillance, Crohn's disease, business.industry, Progressive multifocal leukoencephalopathy, Multiple sclerosis, immune surveillance, PF-00547659, Gastroenterology, Leukoencephalopathy, Progressive Multifocal, Immunosuppression, General Medicine, Original Articles, Middle Aged, medicine.disease, 3. Good health, Immune surveillance, 030104 developmental biology, medicine.anatomical_structure, Immunology, Female, business, Immunosuppressive Agents, medicine.drug |
| الوصف: | Background and Aims: Progressive 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 antiintegrin 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. Methods: Cerebrospinal 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. Results: Patients 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. Conclusions: In 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. SCOPUS: ar.j info:eu-repo/semantics/published |
| وصف الملف: | 2 full-text file(s): application/pdf; application/pdf |
| اللغة: | English |
| تدمد: | 1873-9946 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0350cb62bfc1c41162f6824fc6910661 https://doi.org/10.1093/ecco-jcc/jjx128 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0350cb62bfc1c41162f6824fc6910661 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18739946 |
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