Effect of leflunomide on the peripheral nerves in rheumatoid arthritis

Intern Med J. 2007 Feb;37(2):101-7. doi: 10.1111/j.1445-5994.2007.01266.x.


Background: The objective of this study was to determine the neurophysiological effects of leflunomide on peripheral nerves in rheumatoid arthritis.

Methods: We conducted a prospective cohort trial of 32 patients with rheumatoid arthritis with 16 patients receiving leflunomide treatment and 16 receiving other disease-modifying anti-rheumatic drug therapies. Clinical, laboratory and neurophysiological measurements were used to determine the presence of a peripheral neuropathy in these patients at study entry and then after a further 3 and 6 months.

Results: Fifty-four per cent of the leflunomide group and 8% of the control group had an increase in their neuropathy symptom score 6 months into the study (P = 0.01). No correlation was found between the electrophysiological findings and the clinical symptoms. There was no significant difference between the two groups in upper and lower limb sensory and motor amplitudes and conduction velocities recorded at 3 and 6 months. One patient developed both clinical and neurophysiological evidence of a peripheral neuropathy 5 months into the study that improved after cessation of leflunomide therapy and cholestyramine washout.

Conclusion: After 6 months of exposure we found that leflunomide was associated with an apparent increase in the clinical symptoms of peripheral neuropathy in patients with rheumatoid arthritis. These symptoms did not correlate with neurophysiological studies.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Controlled Clinical Trial

MeSH terms

  • Aged
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / physiopathology
  • Cohort Studies
  • Female
  • Humans
  • Isoxazoles / adverse effects
  • Isoxazoles / pharmacology
  • Isoxazoles / therapeutic use*
  • Leflunomide
  • Male
  • Middle Aged
  • Neuritis / chemically induced
  • Neuritis / physiopathology
  • Peripheral Nerves / drug effects*
  • Peripheral Nerves / physiology
  • Prospective Studies


  • Isoxazoles
  • Leflunomide