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Discontinuation of infliximab therapy in patients with Crohn's disease in sustained complete remission (the STOP IT study): protocol for a double-blind, randomised, placebo-controlled, multicentre trial

INTRODUCTION: Infliximab (IFX), a monoclonal chimeric antibody against tumour necrosis factor (TNF) α, is effective for induction and maintenance of remission in moderate to severe Crohn's disease. Discontinuation of IFX maintenance therapy in patients in remission should be considered in order...

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Autores principales: Buhl, Sine Schnoor, Steenholdt, Casper, Brynskov, Jørn, Thomsen, Ole Østergaard, Bendtzen, Klaus, Ainsworth, Mark Andrew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4275671/
https://www.ncbi.nlm.nih.gov/pubmed/25524543
http://dx.doi.org/10.1136/bmjopen-2014-005887
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author Buhl, Sine Schnoor
Steenholdt, Casper
Brynskov, Jørn
Thomsen, Ole Østergaard
Bendtzen, Klaus
Ainsworth, Mark Andrew
author_facet Buhl, Sine Schnoor
Steenholdt, Casper
Brynskov, Jørn
Thomsen, Ole Østergaard
Bendtzen, Klaus
Ainsworth, Mark Andrew
author_sort Buhl, Sine Schnoor
collection PubMed
description INTRODUCTION: Infliximab (IFX), a monoclonal chimeric antibody against tumour necrosis factor (TNF) α, is effective for induction and maintenance of remission in moderate to severe Crohn's disease. Discontinuation of IFX maintenance therapy in patients in remission should be considered in order to reduce the potential long-term side effects and lower costs. METHODS AND ANALYSIS: This is a prospective, double-blind, randomised, placebo-controlled, multicentre study of patients with luminal Crohn’s disease who have been treated with IFX for at least 1 year and are in sustained complete clinical, biochemical and endoscopic remission (ie, Crohn's Disease Activity Index (CDAI) score <150, complete mucosal healing and biochemical markers of inflammation within the normal range). These patients are randomised to receive placebo infusions or continue IFX maintenance therapy. The primary end point is the proportion of patients in maintained remission after 48 weeks (def. CDAI <150). ETHICS AND DISSEMINATION: It is estimated that the knowledge gained about how to optimally handle patients with Crohn’s disease in complete long-term sustained remission on IFX is proportionate to the risks and inconveniences related to participation in this study. Prolonged exposure to IFX may cause severe side effects and increased risk of malignancies. Conversely, IFX discontinuation should not unnecessarily create a high risk of relapse. Thus, empirical evidence is needed concerning the safety of discontinuing IFX once a patient exhibits sustained remission. Study results will be published in an English language scientific medical journal. The study is approved by the Danish Medicines Agency (EudraCT-number: 2012-002702-51) and the Regional Ethics Committee of Region Hovedstaden Denmark (Approval-number: H-4-2012-099). The project is reported to the Danish Data Protection Agency (ID-number: 2007-58-0015/HEH.750.89-27), registered at Clinicaltrials.gov, and monitored by independent GCP units for the University of Copenhagen, Odense and Aarhus. The current approved protocol is V.3.2, dated 1 June 2014. TRIAL REGISTRATION NUMBER: http://clinicaltrials.gov/show/NCT01817426.
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spelling pubmed-42756712014-12-31 Discontinuation of infliximab therapy in patients with Crohn's disease in sustained complete remission (the STOP IT study): protocol for a double-blind, randomised, placebo-controlled, multicentre trial Buhl, Sine Schnoor Steenholdt, Casper Brynskov, Jørn Thomsen, Ole Østergaard Bendtzen, Klaus Ainsworth, Mark Andrew BMJ Open Gastroenterology and Hepatology INTRODUCTION: Infliximab (IFX), a monoclonal chimeric antibody against tumour necrosis factor (TNF) α, is effective for induction and maintenance of remission in moderate to severe Crohn's disease. Discontinuation of IFX maintenance therapy in patients in remission should be considered in order to reduce the potential long-term side effects and lower costs. METHODS AND ANALYSIS: This is a prospective, double-blind, randomised, placebo-controlled, multicentre study of patients with luminal Crohn’s disease who have been treated with IFX for at least 1 year and are in sustained complete clinical, biochemical and endoscopic remission (ie, Crohn's Disease Activity Index (CDAI) score <150, complete mucosal healing and biochemical markers of inflammation within the normal range). These patients are randomised to receive placebo infusions or continue IFX maintenance therapy. The primary end point is the proportion of patients in maintained remission after 48 weeks (def. CDAI <150). ETHICS AND DISSEMINATION: It is estimated that the knowledge gained about how to optimally handle patients with Crohn’s disease in complete long-term sustained remission on IFX is proportionate to the risks and inconveniences related to participation in this study. Prolonged exposure to IFX may cause severe side effects and increased risk of malignancies. Conversely, IFX discontinuation should not unnecessarily create a high risk of relapse. Thus, empirical evidence is needed concerning the safety of discontinuing IFX once a patient exhibits sustained remission. Study results will be published in an English language scientific medical journal. The study is approved by the Danish Medicines Agency (EudraCT-number: 2012-002702-51) and the Regional Ethics Committee of Region Hovedstaden Denmark (Approval-number: H-4-2012-099). The project is reported to the Danish Data Protection Agency (ID-number: 2007-58-0015/HEH.750.89-27), registered at Clinicaltrials.gov, and monitored by independent GCP units for the University of Copenhagen, Odense and Aarhus. The current approved protocol is V.3.2, dated 1 June 2014. TRIAL REGISTRATION NUMBER: http://clinicaltrials.gov/show/NCT01817426. BMJ Publishing Group 2014-12-18 /pmc/articles/PMC4275671/ /pubmed/25524543 http://dx.doi.org/10.1136/bmjopen-2014-005887 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
spellingShingle Gastroenterology and Hepatology
Buhl, Sine Schnoor
Steenholdt, Casper
Brynskov, Jørn
Thomsen, Ole Østergaard
Bendtzen, Klaus
Ainsworth, Mark Andrew
Discontinuation of infliximab therapy in patients with Crohn's disease in sustained complete remission (the STOP IT study): protocol for a double-blind, randomised, placebo-controlled, multicentre trial
title Discontinuation of infliximab therapy in patients with Crohn's disease in sustained complete remission (the STOP IT study): protocol for a double-blind, randomised, placebo-controlled, multicentre trial
title_full Discontinuation of infliximab therapy in patients with Crohn's disease in sustained complete remission (the STOP IT study): protocol for a double-blind, randomised, placebo-controlled, multicentre trial
title_fullStr Discontinuation of infliximab therapy in patients with Crohn's disease in sustained complete remission (the STOP IT study): protocol for a double-blind, randomised, placebo-controlled, multicentre trial
title_full_unstemmed Discontinuation of infliximab therapy in patients with Crohn's disease in sustained complete remission (the STOP IT study): protocol for a double-blind, randomised, placebo-controlled, multicentre trial
title_short Discontinuation of infliximab therapy in patients with Crohn's disease in sustained complete remission (the STOP IT study): protocol for a double-blind, randomised, placebo-controlled, multicentre trial
title_sort discontinuation of infliximab therapy in patients with crohn's disease in sustained complete remission (the stop it study): protocol for a double-blind, randomised, placebo-controlled, multicentre trial
topic Gastroenterology and Hepatology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4275671/
https://www.ncbi.nlm.nih.gov/pubmed/25524543
http://dx.doi.org/10.1136/bmjopen-2014-005887
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