TY - JOUR
T1 - Demyelinating Disease after Exposure to Tumor Necrosis Factor α Inhibitors
T2 - A Case Series in a Tertiary Care Center
AU - Stienstra, Nicholas
AU - Horton, Joel
AU - Lane, Michael
AU - Kumthekar, Anand
AU - Sathe, Nishad
AU - Sunny, Christy
AU - Yadav, Vijayshree
AU - Deodhar, Atul
N1 - Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/3/1
Y1 - 2022/3/1
N2 - Tumor necrosis factor a inhibitors (TNFi's) are effective treatments for multiple immune-mediated rheumatologic, gastrointestinal, dermatologic, and ophthalmic inflammatory diseases. Although relatively safe, serious adverse effects have been reported, and they carry a US Food and Drug Administration warning for new onset or exacerbation of demyelinating disorders. Tumor necrosis factor a (TNF-a) has pleiotropic actions on the nervous system, able to promote neuroinflammation and damage to myelin in some instances and exert protective effects and remyelination in others.1 Tumor necrosis factor a inhibitors were shown to be protective in studies of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS). However, an open-label clinical trial using infliximab in MS resulted in increased inflammatory activity on magnetic resonance imaging (MRI).2 Additional studies involving TNF-a deficiency and neutralization similarly resulted inMS-like disease.1,3 Despite these associations, randomized controlled trials and postmarketing monitoring did not show increased risk of demyelinating events in patients on TNFi.4,5 Most recently, analysis from an observational cohort of RA patients in the United Kingdom showed a marginally increased but not statistically significant standardized incidence rate of demyelinating disease (DD) after TNFi exposure (1.38; confidence interval, 0.96–1.92), although did not include peripheral demyelinating events.6 It is unclear whether TNFi causes de novo demyelinating disease, triggers preexisting “latent” disease, or is a confounding factor.7 Optimal treatment for TNFi-associated demyelination is also uncertain, with withdrawal of the TNFi, switch to alternatives, high-dose steroids, or therapies for MS all reported in the literature.
AB - Tumor necrosis factor a inhibitors (TNFi's) are effective treatments for multiple immune-mediated rheumatologic, gastrointestinal, dermatologic, and ophthalmic inflammatory diseases. Although relatively safe, serious adverse effects have been reported, and they carry a US Food and Drug Administration warning for new onset or exacerbation of demyelinating disorders. Tumor necrosis factor a (TNF-a) has pleiotropic actions on the nervous system, able to promote neuroinflammation and damage to myelin in some instances and exert protective effects and remyelination in others.1 Tumor necrosis factor a inhibitors were shown to be protective in studies of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS). However, an open-label clinical trial using infliximab in MS resulted in increased inflammatory activity on magnetic resonance imaging (MRI).2 Additional studies involving TNF-a deficiency and neutralization similarly resulted inMS-like disease.1,3 Despite these associations, randomized controlled trials and postmarketing monitoring did not show increased risk of demyelinating events in patients on TNFi.4,5 Most recently, analysis from an observational cohort of RA patients in the United Kingdom showed a marginally increased but not statistically significant standardized incidence rate of demyelinating disease (DD) after TNFi exposure (1.38; confidence interval, 0.96–1.92), although did not include peripheral demyelinating events.6 It is unclear whether TNFi causes de novo demyelinating disease, triggers preexisting “latent” disease, or is a confounding factor.7 Optimal treatment for TNFi-associated demyelination is also uncertain, with withdrawal of the TNFi, switch to alternatives, high-dose steroids, or therapies for MS all reported in the literature.
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U2 - 10.1097/RHU.0000000000001789
DO - 10.1097/RHU.0000000000001789
M3 - Article
C2 - 34538848
AN - SCOPUS:85125011672
SN - 1076-1608
VL - 28
SP - E638-E641
JO - Journal of Clinical Rheumatology
JF - Journal of Clinical Rheumatology
IS - 2
ER -