Clinical features and genetic risk of demyelination following anti-TNF treatment
Lin, S; Green, HD; Hendy, P; et al.Heerasing, NM; Chanchlani, N; Hamilton, B; Walker, GJ; Heap, GA; Hobart, J; Martin, RJ; Coles, AJ; Silverberg, MS; Irving, PM; Chung-Faye, G; Silber, E; Cummings, F; Lytvyak, E; Andersen, V; Wood, AR; Tyrrell, J; Beaumont, RN; Weedon, MN; Kennedy, NA; Spiers, A; Harrower, T; Goodhand, JR; Ahmad, T
Date: 4 May 2020
Article
Journal
Journal of Crohn's and Colitis
Publisher
Oxford University Press (OUP) / European Crohn's and Colitis Organisation (ECCO)
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Abstract
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 test whether affected patients were genetically predisposed to multiple sclerosis (MS). METHODS: We conducted a case-control study to describe the clinical features ...
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 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. We compared genetic risk scores (GRS), calculated using carriage of 43 susceptibility loci for MS, in 48 cases to 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 9 (17%), progressive symptoms in 3 (6%): 2 (4%) patients were diagnosed with MS. There was no significant difference between MS GRS scores in cases (mean -3.5 x 10-4, 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 were more likely female, less frequently treated with an immunomodulator, and had a similar genetic risk to anti-TNF exposed controls who did not. Large prospective studies with pre-treatment neuroimaging are required to identify genetic susceptibility loci.
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