Title :

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

Author(s) :

D''haens, Geert [Auteur]
Vermeire, Severine [Auteur]
Vogelsang, Harald [Auteur]
Allez, Matthieu [Auteur]
Université Paris Diderot - Paris 7 [UPD7]
Desreumaux, Pierre [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Van Gossum, Andre [Auteur]
Sandborn, William J. [Auteur]
Baumgart, Daniel C. [Auteur]
Ransohoff, Richard M. [Auteur]
Comer, Gail M. [Auteur]
Ahmad, Alaa [Auteur]
Cataldi, Fabio [Auteur]
Cheng, John [Auteur]
Clare, Robert [Auteur]
Gorelick, Kenneth J. [Auteur]
Kaminski, Annamarie [Auteur]
Pradhan, Vivek [Auteur]
Rivers, Sunday [Auteur]
Sikpi, Matthew O. [Auteur]
Zhang, Yanhua [Auteur]
Hassan-Zahraee, Mina [Auteur]
Reinisch, Walter [Auteur]
Stuve, Olaf [Auteur]

Journal title :

Journal of Crohn's and Colitis

Abbreviated title :

J. Crohns Colitis

Volume number :

12

Pages :

188-196

Publication date :

2018-02

ISSN :

1873-9946

English keyword(s) :

Crohn's disease
MAdCAM-1
PF-00547659
immune surveillance
inflammatory bowel disease

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

OBJECTIVE: 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 ...
Show more >OBJECTIVE: 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 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. 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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
Inserm
Université de Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Submission date :

2024-01-30T10:27:22Z
2024-03-07T12:22:57Z