JC viral loads in patients with Crohn's disease treated with immunosuppression: can we screen for elevated risk of progressive multifocal leukoencephalopathy?

Verbeeck, Jannick; Assche, Gert Van; Ryding, Janka; Wollants, Elke; Rans, Kato; Vermeire, Séverine; Pourkarim, Mahmoud Reza; Noman, Maja; Dillner, Joakim; Ranst, Marc Van; Rutgeerts, Paul

doi:10.1136/gut.2007.145698

Cited by 54 publications

(39 citation statements)

References 28 publications

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“…It should also be noted that there are a number of interventions available for patients with PML, including antiviral treatment, immunomodulatory therapies, and plasma exchange [Stü ve et al 2007]. Moreover, there are ongoing efforts to identify possible aspects of the JC viral life cycle that might be used in a screening tool to identify those patients at risk of developing PML [Verbeeck et al 2008].…”

Section: Safetymentioning

confidence: 99%

Review: Anti-adhesion molecule therapy for inflammatory bowel disease

Ghosh

Panaccione

2010

Therap Adv Gastroenterol

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Although biologic agents directed against tumor necrosis factor alpha (TNFa) continue to be an effective therapeutic strategy for patients with inflammatory bowel disease (IBD), approximately 30% of patients with Crohn's disease (CD) who are refractory to standard treatment do not respond to induction therapy with TNFa inhibitors and, of those who initially respond, 50% or more cease to respond within a year. Moreover, their use can be associated with significant safety issues. Clearly, there is a need to target alternative pathways involved in the inflammatory process. IBD is driven by the trafficking of lymphocytes from the circulation into the gut tissue that is mediated by adhesive interactions between the lymphocytes and endothelial cells. The adhesion molecules involved represent attractive targets for the development of new therapeutics which should aid in the resolution of existing inflammation, prevent recurrence of inflammation, and may potentially lead to long-term control of disease. In this article we review current opportunities and challenges facing anti-adhesion therapy in IBD, and discusses recent clinical development efforts that have focused on having an impact on two particular adhesive interactions: a 4 -integrin/MAdCAM-1 and b 2 -integrin/ICAM-1. Of particular interest is natalizumab, a humanized monoclonal antibody against human a 4 integrin that is approved for the treatment of patients with moderately-to-severely active CD and evidence of active inflammation. This agent represents an efficacious therapeutic option for patients who do not respond to, or have failed, a TNF-a inhibitor.

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Section: Safetymentioning

confidence: 99%

Review: Anti-adhesion molecule therapy for inflammatory bowel disease

Ghosh

Panaccione

2010

Therap Adv Gastroenterol

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“…Natalizumab prevents α4β1 binding to VCAM and α4β7 binding to MACam-1 and thus prevents T cell extravasation into the brain or gut, respectively. Because both MS and Crohn's disease feature inflammatory T cells as a significant part of the pathology, preventing access of these cells to target organs has substantial clinical effects (45,46). Another humanized monoclonal antibody, efalizumab, binds the α1 integrin molecule CD11a on T and B cells, blocking attachment to the ICAM (intercellular adhesion molecules) on endothelial cells and infiltration into the layers of the skin (47).…”

Section: Pml As a Consequence Of Biological Therapies For Autoimmune mentioning

confidence: 99%

Progressive Multifocal Leukoencephalopathy in Patients on Immunomodulatory Therapies

2010

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“…This lymphoma was fatal in 6 of 8 reported cases. 54,55 Autoimmune phenomena (e.g., development of antidsDNA antibodies) occurred in Ϸ9% of patients treated with infliximab. However, the antibody concentration was low and antibodies were transient, with only rare reports of druginduced lupus-like syndromes.…”

Section: Safety Issuesmentioning

confidence: 99%

Positioning biologic agents in the treatment of Crohnʼs disease

Hanauer

2009

Inflammatory Bowel Diseases

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One decade after the emergence of biologic therapy for Crohn's disease (CD), our treatment algorithms are beginning to change. Once reserved for patients with refractory disease, disease unresponsive to conventional therapies, or those requiring multiple courses of corticosteroids, there is increasing evidence that early, aggressive interventions with immunosuppressants or biologic therapies targeting tumor necrosis factor-alpha or alpha-4 integrins can alter the natural history of CD by reducing the transmural complications of structuring and fistulization and the nearly inevitable requisite for surgical resections. More recent trials are beginning to suggest that intervention with combination therapy for selected patients with a poor prognosis may modify the long-term course of CD. Selection of patients with features predicting a complex or progressive course and early, combined intervention is now possible. Future studies are still needed to best identify predictors of response to individual agents with differing mechanisms of action, as well as to optimize the risk-benefit of long-term maintenance therapy.

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JC viral loads in patients with Crohn's disease treated with immunosuppression: can we screen for elevated risk of progressive multifocal leukoencephalopathy?

Cited by 54 publications

References 28 publications

Review: Anti-adhesion molecule therapy for inflammatory bowel disease

Review: Anti-adhesion molecule therapy for inflammatory bowel disease

Progressive Multifocal Leukoencephalopathy in Patients on Immunomodulatory Therapies

Positioning biologic agents in the treatment of Crohnʼs disease

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