Neurological events with tumour necrosis factor alpha inhibitors reported to the Food and Drug Administration Adverse Event Reporting System

Background: The association between inhibition of tumour necrosis factor alpha (TNF-α) and new onset of neurological adverse events (AEs) is unclear.

Aims: To evaluate neurological AEs with TNF-α inhibitors reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) utilising a standardised scoring tool for drug-induced AEs.

Methods: A search of FAERS for neurological AEs (January 1, 2000 to December 31, 2009) reported with infliximab, adalimumab, certolizumab and etanercept was performed. Full-text reports were accessed using the Freedom of Information Act and scored using Naranjo score, while accounting for temporal association, previous conclusive reports of the neurological AE with any TNF-α inhibitor, and alternate explanations including underlying disease, concomitant medications and comorbidities, such as diabetes mellitus.

Results: There were 772 reports. Most were in patients who had rheumatoid arthritis (393, 50.9%) followed by inflammatory bowel disease (140, 18.1%). No significant differences in age or gender were seen between IBD patients compared with rheumatological diseases (P = 0.584 and P = 0.055 respectively). Etanercept was reported most (327, 42.4%) followed by infliximab (276, 35.8%) (P = 0.008). Peripheral neuropathy was the most common neurological AE (296 reports, 38.3%) followed by central nervous system and/or spinal cord demyelination (153 reports, 19.8%). Majority (551, 71.4%) of the reports were of 'possible' AE with the remaining 'probable' AE and none identified as 'definite' AE.

Conclusion: While several neurological AEs have been described, definite association between de novo development of these AEs and exposure to TNF-α inhibitors was not established using the Naranjo score.