Demyelination during tumour necrosis factor antagonist therapy for psoriasis: a case report and review of the literature

Abstract

Central nervous system (CNS) demyelination in a patient receiving tumour necrosis factor alpha (TNF-α) antagonist therapy in our practice prompted a search of the literature to assess the evidence for a causal relationship between TNF antagonist therapy and demyelination. We summarise clinical data extracted on 65 reported cases of CNS demyelination in patients receiving TNF antagonist therapy and show that the data are consistent with a drug-related aetiology given the temporal relationship between TNF antagonist initiation and symptoms, de-challenge–re-challenge phenomenon and the later age of disease onset compared with sporadic multiple sclerosis. Research on TNF signalling pathways also suggests a plausible causative role of TNF antagonist therapy in demyelination. However to date, controlled trial and pharmacovigilance data do not show an increased risk of demyelination in patients receiving TNF antagonist therapy. These data may be underpowered to exclude such a risk and pooled, collaborative data from multiple registries are warranted. Given the uncertainty in this area, clinicians should adhere to existing clinical guidance advising avoidance of TNF antagonist therapy in patients with a personal or family history of demyelination, and ensure all suitable patients are enrolled in long term safety registries in countries where these are established.

Key words::

• TNF antagonist
• demyelination
• multiple sclerosis
• psoriasis
• infliximab
• etanercept
• adalimumab

Declaration of interest: Funding sources: Financial support from the Department of Health via the National Institute for Health Research comprehensive Biomedical Research Centre award to Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital Foundation Trust. CH Smith has received research support from Pfizer, Schering Plough, Janssen Cilag and Abbott. JNWN Barker has acted as consultant for or given talks at sponsored symposia for Abbott, Merck, Pfizer, Novartis, Amgen and Eli-Lily. SK Mahil, TC Andrews and C Brierley report no conflicts of interest.