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

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.

Citation

Lin, S., Green, H. D., Hendy, P., Heerasing, N. M., Chanchlani, N., Hamilton, B., Walker, G. J., Heap, G. A., Hobart, J., Martin, R. J., Coles, A. J., Silverberg, M. S., Irving, P. M., Chung-Faye, G., Silber, E., Cummings, J. R. F., Lytvyak, E., Andersen, V., Wood, A. R., Tyrrell, J., … Ahmad, T. (2020). Clinical Features and Genetic Risk of Demyelination Following Anti-TNF Treatment. Journal of Crohn's & colitis, 14(12), 1653–1661. https://doi.org/10.1093/ecco-jcc/jjaa104

DOI

10.1093/ecco-jcc/jjaa104

URI

https://hdl.handle.net/20.500.14709/755