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Anti-TNF therapy for inflammatory bowel disease in patients with neurodegenerative Niemann-Pick disease Type C

Background:  Blockade of tumour necrosis factor (anti-TNF) is effective in patients with Crohn’s Disease but has been associated with infection risk and neurological complications such as demyelination. Niemann-Pick disease Type C1 (NPC1) is a lysosomal storage disorder presenting in childhood with...

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Autores principales: Williams, Isabelle, Pandey, Sumeet, Haller, Wolfram, Huynh, Hien Quoc, Chan, Alicia, Düeker, Gesche, Bettels, Ruth, Peyrin-Biroulet, Laurent, Dike, Chinenye R., DeGeeter, Catherine, Smith, David, Al Eisa, Nada, Platt, Nick, Marquardt, Thorsten, Schwerd, Tobias, Platt, Frances M., Uhlig, Holm H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: F1000 Research Limited 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171292/
https://www.ncbi.nlm.nih.gov/pubmed/35694196
http://dx.doi.org/10.12688/wellcomeopenres.16986.1
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author Williams, Isabelle
Pandey, Sumeet
Haller, Wolfram
Huynh, Hien Quoc
Chan, Alicia
Düeker, Gesche
Bettels, Ruth
Peyrin-Biroulet, Laurent
Dike, Chinenye R.
DeGeeter, Catherine
Smith, David
Al Eisa, Nada
Platt, Nick
Marquardt, Thorsten
Schwerd, Tobias
Platt, Frances M.
Uhlig, Holm H.
author_facet Williams, Isabelle
Pandey, Sumeet
Haller, Wolfram
Huynh, Hien Quoc
Chan, Alicia
Düeker, Gesche
Bettels, Ruth
Peyrin-Biroulet, Laurent
Dike, Chinenye R.
DeGeeter, Catherine
Smith, David
Al Eisa, Nada
Platt, Nick
Marquardt, Thorsten
Schwerd, Tobias
Platt, Frances M.
Uhlig, Holm H.
author_sort Williams, Isabelle
collection PubMed
description Background:  Blockade of tumour necrosis factor (anti-TNF) is effective in patients with Crohn’s Disease but has been associated with infection risk and neurological complications such as demyelination. Niemann-Pick disease Type C1 (NPC1) is a lysosomal storage disorder presenting in childhood with neurological deterioration, liver damage and respiratory infections. Some NPC1 patients develop severe Crohn’s disease. Our objective was to investigate the safety and effectiveness of anti-TNF in NPC1 patients with Crohn’s disease. Methods: Retrospective data on phenotype and therapy response were collected in 2019-2020 for the time period 2014 to 2020 from patients in the UK, France, Germany and Canada with genetically confirmed NPC1 defects and intestinal inflammation. We investigated TNF secretion in peripheral blood mononuclear cells treated with NPC1 inhibitor in response to bacterial stimuli . Results: NPC1 inhibitor treated peripheral blood mononuclear cells (PBMCs) show significantly increased TNF production after lipopolysaccharide or bacterial challenge providing a rationale for anti-TNF therapy. We identified 4 NPC1 patients with Crohn’s disease (CD)-like intestinal inflammation treated using anti-TNF therapy (mean age of onset 8.1 years, mean treatment length 27.75 months, overall treatment period 9.25 patient years). Anti-TNF therapy was associated with reduced gastrointestinal symptoms with no apparent adverse neurological events. Therapy improved intestinal inflammation in 4 patients. Conclusions: Anti-TNF therapy appears safe in patients with NPC1 and is an effective treatment strategy for the management of intestinal inflammation in these patients.
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spelling pubmed-91712922022-06-10 Anti-TNF therapy for inflammatory bowel disease in patients with neurodegenerative Niemann-Pick disease Type C Williams, Isabelle Pandey, Sumeet Haller, Wolfram Huynh, Hien Quoc Chan, Alicia Düeker, Gesche Bettels, Ruth Peyrin-Biroulet, Laurent Dike, Chinenye R. DeGeeter, Catherine Smith, David Al Eisa, Nada Platt, Nick Marquardt, Thorsten Schwerd, Tobias Platt, Frances M. Uhlig, Holm H. Wellcome Open Res Research Article Background:  Blockade of tumour necrosis factor (anti-TNF) is effective in patients with Crohn’s Disease but has been associated with infection risk and neurological complications such as demyelination. Niemann-Pick disease Type C1 (NPC1) is a lysosomal storage disorder presenting in childhood with neurological deterioration, liver damage and respiratory infections. Some NPC1 patients develop severe Crohn’s disease. Our objective was to investigate the safety and effectiveness of anti-TNF in NPC1 patients with Crohn’s disease. Methods: Retrospective data on phenotype and therapy response were collected in 2019-2020 for the time period 2014 to 2020 from patients in the UK, France, Germany and Canada with genetically confirmed NPC1 defects and intestinal inflammation. We investigated TNF secretion in peripheral blood mononuclear cells treated with NPC1 inhibitor in response to bacterial stimuli . Results: NPC1 inhibitor treated peripheral blood mononuclear cells (PBMCs) show significantly increased TNF production after lipopolysaccharide or bacterial challenge providing a rationale for anti-TNF therapy. We identified 4 NPC1 patients with Crohn’s disease (CD)-like intestinal inflammation treated using anti-TNF therapy (mean age of onset 8.1 years, mean treatment length 27.75 months, overall treatment period 9.25 patient years). Anti-TNF therapy was associated with reduced gastrointestinal symptoms with no apparent adverse neurological events. Therapy improved intestinal inflammation in 4 patients. Conclusions: Anti-TNF therapy appears safe in patients with NPC1 and is an effective treatment strategy for the management of intestinal inflammation in these patients. F1000 Research Limited 2022-01-11 /pmc/articles/PMC9171292/ /pubmed/35694196 http://dx.doi.org/10.12688/wellcomeopenres.16986.1 Text en Copyright: © 2022 Williams I et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Williams, Isabelle
Pandey, Sumeet
Haller, Wolfram
Huynh, Hien Quoc
Chan, Alicia
Düeker, Gesche
Bettels, Ruth
Peyrin-Biroulet, Laurent
Dike, Chinenye R.
DeGeeter, Catherine
Smith, David
Al Eisa, Nada
Platt, Nick
Marquardt, Thorsten
Schwerd, Tobias
Platt, Frances M.
Uhlig, Holm H.
Anti-TNF therapy for inflammatory bowel disease in patients with neurodegenerative Niemann-Pick disease Type C
title Anti-TNF therapy for inflammatory bowel disease in patients with neurodegenerative Niemann-Pick disease Type C
title_full Anti-TNF therapy for inflammatory bowel disease in patients with neurodegenerative Niemann-Pick disease Type C
title_fullStr Anti-TNF therapy for inflammatory bowel disease in patients with neurodegenerative Niemann-Pick disease Type C
title_full_unstemmed Anti-TNF therapy for inflammatory bowel disease in patients with neurodegenerative Niemann-Pick disease Type C
title_short Anti-TNF therapy for inflammatory bowel disease in patients with neurodegenerative Niemann-Pick disease Type C
title_sort anti-tnf therapy for inflammatory bowel disease in patients with neurodegenerative niemann-pick disease type c
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171292/
https://www.ncbi.nlm.nih.gov/pubmed/35694196
http://dx.doi.org/10.12688/wellcomeopenres.16986.1
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