Clinical Features and Genetic Risk of Demyelination Following Anti-TNF Treatment.


Journal

Journal of Crohn's & colitis
ISSN: 1876-4479
Titre abrégé: J Crohns Colitis
Pays: England
ID NLM: 101318676

Informations de publication

Date de publication:
02 Dec 2020
Historique:
pubmed: 5 6 2020
medline: 3 2 2022
entrez: 5 6 2020
Statut: ppublish

Résumé

Anti-TNF exposure has been linked to demyelination events. We sought to describe the clinical features of demyelination events following anti-TNF treatment and to test whether affected patients were genetically predisposed to multiple sclerosis [MS]. We conducted a case-control study to describe the clinical features of demyelination events following anti-TNF exposure. We compared genetic risk scores [GRS], calculated using carriage of 43 susceptibility loci for MS, in 48 cases with 1219 patients exposed to anti-TNF who did not develop demyelination. Overall, 39 [74%] cases were female. The median age [range] of patients at time of demyelination was 41.5 years [20.7-63.2]. The median duration of anti-TNF treatment was 21.3 months [0.5-99.4] and 19 [36%] patients were receiving concomitant immunomodulators. Most patients had central demyelination affecting the brain, spinal cord, or both. Complete recovery was reported in 12 [23%] patients after a median time of 6.8 months [0.1-28.7]. After 33.0 months of follow-up, partial recovery was observed in 29 [55%] patients, relapsing and remitting episodes in nine [17%], progressive symptoms in three [6%]: two [4%] patients were diagnosed with MS. There was no significant difference between MS GRS scores in cases (mean -3.5 × 10-4, standard deviation [SD] 0.0039) and controls [mean -1.1 × 10-3, SD 0.0042] [p = 0.23]. Patients who experienced demyelination events following anti-TNF exposure were more likely female, less frequently treated with an immunomodulator, and had a similar genetic risk to anti-TNF exposed controls who did not experience demyelination events. Large prospective studies with pre-treatment neuroimaging are required to identify genetic susceptibility loci.

Sections du résumé

BACKGROUND BACKGROUND
Anti-TNF exposure has been linked to demyelination events. We sought to describe the clinical features of demyelination events following anti-TNF treatment and to test whether affected patients were genetically predisposed to multiple sclerosis [MS].
METHODS METHODS
We conducted a case-control study to describe the clinical features of demyelination events following anti-TNF exposure. We compared genetic risk scores [GRS], calculated using carriage of 43 susceptibility loci for MS, in 48 cases with 1219 patients exposed to anti-TNF who did not develop demyelination.
RESULTS RESULTS
Overall, 39 [74%] cases were female. The median age [range] of patients at time of demyelination was 41.5 years [20.7-63.2]. The median duration of anti-TNF treatment was 21.3 months [0.5-99.4] and 19 [36%] patients were receiving concomitant immunomodulators. Most patients had central demyelination affecting the brain, spinal cord, or both. Complete recovery was reported in 12 [23%] patients after a median time of 6.8 months [0.1-28.7]. After 33.0 months of follow-up, partial recovery was observed in 29 [55%] patients, relapsing and remitting episodes in nine [17%], progressive symptoms in three [6%]: two [4%] patients were diagnosed with MS. There was no significant difference between MS GRS scores in cases (mean -3.5 × 10-4, standard deviation [SD] 0.0039) and controls [mean -1.1 × 10-3, SD 0.0042] [p = 0.23].
CONCLUSIONS CONCLUSIONS
Patients who experienced demyelination events following anti-TNF exposure were more likely female, less frequently treated with an immunomodulator, and had a similar genetic risk to anti-TNF exposed controls who did not experience demyelination events. Large prospective studies with pre-treatment neuroimaging are required to identify genetic susceptibility loci.

Identifiants

pubmed: 32497177
pii: 5851416
doi: 10.1093/ecco-jcc/jjaa104
doi:

Substances chimiques

Tumor Necrosis Factor Inhibitors 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1653-1661

Subventions

Organisme : CORE
Organisme : iSAEC

Commentaires et corrections

Type : CommentIn

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Auteurs

Simeng Lin (S)

IBD Pharmacogenetics Group, University of Exeter, Exeter, UK.
Department of Gastroenterology, Royal Devon and Exeter Hospital NHS Foundation Trust, Exeter, UK.

Harry D Green (HD)

IBD Pharmacogenetics Group, University of Exeter, Exeter, UK.

Peter Hendy (P)

IBD Pharmacogenetics Group, University of Exeter, Exeter, UK.
Department of Gastroenterology, Royal Devon and Exeter Hospital NHS Foundation Trust, Exeter, UK.

Neel M Heerasing (NM)

IBD Pharmacogenetics Group, University of Exeter, Exeter, UK.
Department of Gastroenterology, Royal Devon and Exeter Hospital NHS Foundation Trust, Exeter, UK.

Neil Chanchlani (N)

IBD Pharmacogenetics Group, University of Exeter, Exeter, UK.

Benjamin Hamilton (B)

IBD Pharmacogenetics Group, University of Exeter, Exeter, UK.

Gareth J Walker (GJ)

IBD Pharmacogenetics Group, University of Exeter, Exeter, UK.
Department of Gastroenterology, Royal Devon and Exeter Hospital NHS Foundation Trust, Exeter, UK.

Graham A Heap (GA)

IBD Pharmacogenetics Group, University of Exeter, Exeter, UK.
Department of Gastroenterology, Royal Devon and Exeter Hospital NHS Foundation Trust, Exeter, UK.

Jeremy Hobart (J)

Department of Neurology, University Hospitals Plymouth, Plymouth, UK.

Roswell J Martin (RJ)

Department of Neurology, Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK.

Alasdair J Coles (AJ)

Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Mark S Silverberg (MS)

Mount Sinai Hospital Inflammatory Bowel Disease Centre, University of Toronto, Toronto, ON, Canada.

Peter M Irving (PM)

Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

Guy Chung-Faye (G)

Department of Gastroenterology, King's College Hospital, London, UK.

Eli Silber (E)

Department of Neurology, King's College Hospital, London, UK.

J R Fraser Cummings (JRF)

Department of Gastroenterology, Southampton General Hospital, Southampton, UK.

Ellina Lytvyak (E)

Department of Medicine, University of Alberta, Edmonton, AB, Canada.

Vibeke Andersen (V)

Focussed Research Unit for Molecular Diagnostic and Clinical Research, IRS-Center Soenderjylland, University Hospital of Southern Denmark, Odense, Denmark.

Andrew R Wood (AR)

University of Exeter, Medical School, Exeter, UK.

Jessica Tyrrell (J)

University of Exeter, Medical School, Exeter, UK.

Robin N Beaumont (RN)

University of Exeter, Medical School, Exeter, UK.

Michael N Weedon (MN)

University of Exeter, Medical School, Exeter, UK.

Nicholas A Kennedy (NA)

IBD Pharmacogenetics Group, University of Exeter, Exeter, UK.
Department of Gastroenterology, Royal Devon and Exeter Hospital NHS Foundation Trust, Exeter, UK.

Alexander Spiers (A)

Department of Radiology, Royal Devon and Exeter Hospital NHS Foundation Trust, Exeter, UK.

Timothy Harrower (T)

Department of Neurology, Royal Devon and Exeter Hospital NHS Foundation Trust, Exeter, UK.

James R Goodhand (JR)

IBD Pharmacogenetics Group, University of Exeter, Exeter, UK.
Department of Gastroenterology, Royal Devon and Exeter Hospital NHS Foundation Trust, Exeter, UK.

Tariq Ahmad (T)

IBD Pharmacogenetics Group, University of Exeter, Exeter, UK.
Department of Gastroenterology, Royal Devon and Exeter Hospital NHS Foundation Trust, Exeter, UK.

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