Clinical Features and Genetic Risk of Demyelination following Anti-TNF Treatment

TY - JOUR

T1 - Clinical Features and Genetic Risk of Demyelination following Anti-TNF Treatment

AU - PRED4 study group

AU - Lin, Simeng

AU - Green, Harry D.

AU - Hendy, Peter

AU - Heerasing, Neel M.

AU - Chanchlani, Neil

AU - Hamilton, Benjamin

AU - Walker, Gareth J.

AU - Heap, Graham A.

AU - Hobart, Jeremy

AU - Martin, Roswell J.

AU - Coles, Alasdair J.

AU - Silverberg, Mark S.

AU - Irving, Peter M.

AU - Chung-Faye, Guy

AU - Silber, Eli

AU - Cummings, J. R.Fraser

AU - Lytvyak, Ellina

AU - Andersen, Vibeke

AU - Wood, Andrew R.

AU - Tyrrell, Jessica

AU - Beaumont, Robin N.

AU - Weedon, Michael N.

AU - Kennedy, Nicholas A.

AU - Spiers, Alexander

AU - Harrower, Timothy

AU - Goodhand, James R.

AU - Ahmad, Tariq

N1 - Funding Information: This work was supported by Guts UK [CORE] and the international Serious Adverse Events Consortium [iSAEC] who funded the study. Publisher Copyright: © 2020 The Author(s). Published by Oxford University Press on behalf of European Crohn's and Colitis Organisation. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2020/12/1

Y1 - 2020/12/1

N2 - 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: 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: 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: 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.

AB - 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: 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: 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: 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.

KW - anti-TNF

KW - Demyelination

UR - http://www.scopus.com/inward/record.url?scp=85098975012&partnerID=8YFLogxK

U2 - 10.1093/ecco-jcc/jjaa104

DO - 10.1093/ecco-jcc/jjaa104

M3 - Article

C2 - 32497177

AN - SCOPUS:85098975012

SN - 1873-9946

VL - 14

SP - 1653

EP - 1661

JO - Journal of Crohn's and Colitis

JF - Journal of Crohn's and Colitis

IS - 12

ER -