Anti-TNF agents and demyelination
Demyelination events following exposure to anti-TNF drugs, as well as clinical and radiological exacerbation of exist-ing multiple sclerosis (MS), have been reported in case reports and clinical trials.
These events might be explained by shared genetic susceptibility to inflammatory disorders including MS. However experimental data suggests a pivotal role for TNF and the TNF receptor systems in the pathogenesis of MS, suggest-ing a possible causal association between the use of anti-TNF therapy and demyelination events. A recent study showed that a single nucleotide polymorphism (SNP) in TNFRSF1 gene (which encodes TNF– receptor 1) was associ-ated with MS but not with other autoimmune diseases. Genetic evidence implicates this SNP as the causal variant for MS. Functional studies show that this risk allele directs expression of a novel, soluble form of TNFR1 that can block TNF 1. So, our study may provide insights about pathogenesis of MS as well.
The Primary Objective is to identify predictive genetic markers (through Genome wide association analysis and subsequent sequencing) so that these drugs can be avoided, or monitoring intensified, in genetically high risk patients
(a) to understand the mechanisms underlying drug side effects
(b) to learn about particular functional chemical groups which predispose to toxicity, & thereby facilitate more rational drug design.
(c) to develop a network of interested UK clinicians for further pharmacogenetic research projects
This is a case-control pharmacogenetic association study with 150 patients and 1200 control subjects. Inclusion criteria include:
• History of exposure to anti TNF-α antibody at any time in the past.
• No history of demyelinating neurological symptoms prior to exposure to anti TNF-α antibody.
• Neurological symptoms lasting at least 24 hours.
• MRI brain and/or spinal cord shows changes consistent with CNS demyelination or electrophysiological studies (nerve conduction or evoked potentials) are consistent with PNS or CNS demyelination and confirmed by a neurologist.
• Neurological opinion implicates anti TNF-α medication as possible cause of demyelination, and if the patient is still receiving the drug, it is withdrawn.
Participation involves attendance at a single 20 minute research visit at the patient’s local hospital for blood samples, completion of a patient questionnaire and a case report form.
For the latest CRF for the anti-TNF induced demyelination (TNF), please click on the link below.
We need your help to identify historical or current patients for this study!
If you can recall any potentially eligible patients please contact Claire Bewshea (Claire.firstname.lastname@example.org) and we will put you in contact with your local principal investigator