Background/Purpose:  There are currently five anti-TNF agents that have been approved for various autoimmune illnesses.  There is no convincing evidence that any one of these is superior to the others in terms of efficacy. However, some differences in safety, such as tuberculosis risk, have been described.  There is no single source of information on the safety of these agents that is universally precise.  The Adverse Event Reporting System (AERS) maintained by the US Food and Drug Administration (FDA) receives spontaneous reports of adverse reactions to approved medications licensed for use in the United States. These are submitted by health care professionals or through the manufacturer. It is widely accepted that this type of reporting underestimates the number of actual cases of toxicity that occur and at times may be biased. Therefore any comparisons should be approached with caution. We sought to evaluate the frequency and type of neurologic events seen with TNF inhibitor (TNFi) therapy.

Methods: The AERS database was queried to identify neurological toxicity events following TNFi use reported from date of approval to end 2011 for etanercept, infliximab, adalimumab, golimumab and certolizumab.  The frequency of these events is influence by time and total market exposure for each agent. Groupings of preferred terms were used to retrieve the following adverse events: acoustic neuritis (AN), central demyelination other (CDO), chronic inflammatory demyelinating polyneuropathy (CIDP), demyelination NOS (DN), Guillain-Barre (GB), multiple sclerosis (MS), optic neuritis (ON), and peripheral neuropathy (PN). The results were calculated as report proportions, i.e. number of cumulative AE reports divided by number of cumulative total reports and expressed as percentages.

 

Results: The following cumulative report proportions were calculated from data received in AERS between the time of initial marketing through December 2011 (values in %).   Neurologic Event Reported Etan Infl Adal Goli Cert             Acoustic Neuritis 0.00 0.00 0.00 0.00 0.00 Central Demyelination Other 0.00 0.00 0.00 0.00 0.00 Chronic Inflammatory Demyelinating Polyneuropathy 0.01 0.02 0.00 0.00 0.00 Demyelination NOS 0.12 0.36 0.10 0.00 0.07 Guillain Barre 0.04 0.17 0.06 0.00 0.01 Multiple Sclerosis 0.18 0.15 0.15 0.35 0.02 Optic Neuritis 0.08 0.14 0.06 0.12 0.08 Peripheral Neuropathy 0.20 0.41 0.17 0.00 0.20             Presumed Central Toxicity1 0.38 0.65 0.32 0.47 0.16 Presumed Peripheral Toxicity2 0.25   0.60   0.23   0.00   0.21                 1.   AN + CDO + DN + MS + ON              2. CIDP + GB + PN                       *All adverse events were coded using MedDRA; **NOS=Not Otherwise Specified.   Conclusion: From initial marketing in 1998 until December 31 2011 patients treated with different anti-TNF agents exhibited differing patterns of neurological injury. Compared to other anti-TNF agents, presumed central demyelination and conditions such as multiple sclerosis were less likely to be reported in patients receiving certolizumab.  The peripheral nerve events, Guillain-Barre and peripheral neuropathy, were more likely to be reported in patients receiving infliximab, as were non-specific terms that referred only to demyelination (DN). Golimumab had no peripheral neurological events, but had disproportionately more multiple sclerosis.  Although spontaneously reported data does not allow conclusions regarding causality, these results suggest that different anti-TNF agents may be associated with different rates of adverse neurological effects and with different sites of neurotoxicity within the nervous system.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/divergent-toxicity-of-tnf-inhibitors-on-demyelinating-disorders-and-neurological-events/