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DEMYELINATION COMPLICATING ANTI–TNF THERAPY IN INFLAMMATORY BOWEL DISEASE (IBD) AND OTHER INFLAMMATORY DISORDERS (PRED4–UKCRN 11988)
  1. Tariq Ahmad
  1. Royal Devon & Exeter

    Abstract

    Background The UK IBD Genetics consortium are conducting a series of studies (PRED4) investigating the genetics of rare adverse reactions to drugs commonly used in gastroenterology. The studies are supported by the International Serious Adverse Events Consortium and are open in most UK hospitals. The primary objective of PRED4 is to identify predictive genetic markers so that these drugs can be avoided, or monitoring intensified, in genetically high risk patients. The secondary objectives are: (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.

    PRED4 includes a study of demyelination complicating anti–TNF therapy in IBD and other inflammatory disorders. New demyelination events following exposure to anti–TNF drugs, as well as clinical and radiological exacerbation of existing 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, suggesting a possible causal association between the use of anti–TNF therapy and demyelination events.

    Methods 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anti TNF–α medication as possible cause of demyelination, and if the patient is still receiving the drug, it is withdrawn.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 and completion of a case report form.

    We need your help to identify historical or current patients for this study! Recruitment to the other study arms of PRED4 is on target, but we are struggling to identify patients with demyelination events following anti–TNF therapy. If you can recall any potentially eligible patients please contact Dr Tariq Ahmad: tariq.ahmad1@nhs.net or Claire Bewshea: Claire.bewshea@nhs.net and we will put you in contact with your local principal investigator. Alternatively please contact the BNSU.

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