Demyelination occurring during anti-tumor necrosis factor alpha therapy for inflammatory arthritides

Arthritis Rheum. 2001 Dec;44(12):2862-9. doi: 10.1002/1529-0131(200112)44:12<2862::aid-art474>;2-w.


Objective: To review the occurrence of neurologic events suggestive of demyelination during anti-tumor necrosis factor alpha (anti-TNFalpha) therapy for inflammatory arthritides.

Methods: The Adverse Events Reporting System of the Food and Drug Administration (FDA) was queried following a report of a patient with refractory rheumatoid arthritis who developed confusion and difficulty with walking after receiving etanercept for 4 months.

Results: Nineteen patients with similar neurologic events were identified from the FDA database, 17 following etanercept administration and 2 following infliximab administration for inflammatory arthritis. All neurologic events were temporally related to anti-TNFalpha therapy, with partial or complete resolution on discontinuation. One patient exhibited a positive rechallenge phenomenon.

Conclusion: Further surveillance and studies are required to better define risk factors for and frequency of adverse events and their relationship to anti-TNFalpha therapies. Until more long-term safety data are available, consideration should be given to avoiding anti-TNFalpha therapy in patients with preexisting multiple sclerosis and to discontinuing anti-TNFalpha therapy immediately when new neurologic signs and symptoms occur, pending an appropriate evaluation.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Adverse Drug Reaction Reporting Systems
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / drug therapy*
  • Biopsy
  • Brain / pathology
  • Contraindications
  • Demyelinating Diseases / etiology*
  • Demyelinating Diseases / pathology
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / adverse effects*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / immunology*


  • Antirheumatic Agents
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Etanercept