Demyelinating Disease following Anti-TNFa Treatment: A Causal or Coincidental Association? Report of Four Cases and Review of the Literature

Abstract

Tumor necrosis factor antagonists (anti-TNFa) are an established therapeutic option for several autoimmune and inflammatory bowel diseases. Despite their clinical effectiveness, neurological adverse events have been reported and literature data suggest a potential role of anti-TNFa in the induction of demyelination of the CNS. We present four patients treated with anti-TNFa who developed symptoms suggestive of CNS demyelination. The first patient, a 17-year-old male who received etanercept for psoriatic arthritis for eight months, presented with dysesthesias up to T4 level. The second patient, a 30-year-old male treated with adalimumab for three years due to ankylosing spondylitis, presented with right unilateral tinnitus. The third case, a 47-year-old female, received etanercept for four years because of psoriatic arthritis and developed persistent headache and left-sided face and head numbness. Finally, the fourth patient, a 57-years-old female treated with etanercept for six years due to ankylosing spondylitis, presented with difficulty in speech, swallowing, and ptosis of the right corner of the mouth. In all cases, brain MRI showed lesions suggestive of demyelination, while positive oligoclonal bands were detected in the CSF. Anti-TNFa treatments were discontinued and patients showed clinical improvement with pulsed intravenous corticosteroid therapy. CNS demyelination following anti-TNFa treatment represents a relatively rare but potential serious complication. Close follow-up and MRI monitoring of these patients is mandatory to elucidate whether the clinical manifestations represent adverse events occurring during anti-TNFa therapy or a first demyelinating episode.

Demyelination and other neurological adverse events after anti-TNF therapy

“…Nozak et al reported seven cases including five cases of peripheral neuropathies [32]. Recently, Andreadou et al reported four additional demyelinating CNS diseases following anti-TNF therapy [37].…”

Co-Existence of Relapsing Remitting Multiple Sclerosis and HLA B27 Positive Ankylosing Spondylitis in a Malay Male: A Rare Occurrence

“…We believe vigorous future studies will bring us to the answer of the association between AS and MS [9][10][11][12][13][14][15].…”

Therapeutic Antibody‐Based Drugs in the Treatment of Human Inflammatory Disorders

“…The spectrum of clinical presentation of demyelinating events includes optic neuritis, MS-like symptoms of paralysis, demyelinating neuropathies, or Guillain-Barre syndrome (for a recent review, see [137]). The incidence of these conditions in the general populations is normally quite low, but it is accepted that some patients develop these conditions within a few months of starting anti-TNF therapies [138,139]. In fact, MS as an existing condition is strongly contraindicated for the use of anti-TNF therapeutics, and, as expected, cessation of anti-TNF drugs is mandated if demyelinating symptoms occur [140].…”

“…These unfortunate adverse events resulted in a decision by Amgen and AstraZeneca to offload the drug to another pharma company, the Canadian-based multinational Valeant Pharmaceuticals and Kyowa Hakko Kirin Company in Japan [83]. Nevertheless, the lack of any negative psychological symptoms when using Ixekizumab (an IL-17A-neutralising mAb) indicates that IL-17A itself (Images adapted from [138] in compliance with copyright).…”