Peripheral neuropathy associated with leflunomide: is there a risk patient profile?

Pharmacoepidemiol Drug Saf. 2007 Jan;16(1):74-8. doi: 10.1002/pds.1282.


Purpose: (i) To monitor the potential clinical neurotoxic symptoms in patients treated with leflunomide in daily practice and (ii) to describe the characteristics of patients presenting with this peripheral nervous system symptoms.

Method: All patients treated with leflunomide between May 2000 and April 2003 and followed in the rheumatology department of the University Hospital participated in the study. Data concerning treatment patterns with leflunomide, demographic and disease characteristics were obtained from clinical charts. Neuropathy was diagnosed with nerve conduction study (NCS). Cases of neuropathy were described and then compared to other patients using univariate analyses.

Results: One hundred and thirteen patients were included in the study. M/F sex ratio was 0.45. Mean age at start of treatment was 55.6 years (range = 27-81). During the study period, eight incident cases of peripheral neuropathy and two cases of worsening of preexisting neuropathy were reported (incidence: 9.8%). Compared with other patients, neuropathy cases were older (69 vs. 54 years, p = 0.0006), more often diabetic (30% vs. 2.9%, p = 0.009) and more often treated with potentially neurotoxic drugs (20% vs. 1.9%, p = 0.039). At least one risk factor (potentially neurotoxic drug or diabetes) was found in 50% of patients with neuropathy versus 4% of patients without neuropathy (56% PPV, 96% NPV).

Conclusion: Cases of toxic neuropathy have been observed during treatment of rheumatoid arthritis with leflunomide. Their occurrence seems to be associated with known risk factors. Careful monitoring of the patient's neurological status during leflunomide treatment is therefore mandatory.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / drug therapy*
  • Diabetes Complications / diagnosis
  • Diabetes Complications / etiology
  • Female
  • Humans
  • Isoxazoles / adverse effects*
  • Isoxazoles / therapeutic use
  • Leflunomide
  • Male
  • Middle Aged
  • Neurologic Examination / methods
  • Peripheral Nervous System Diseases / chemically induced*
  • Peripheral Nervous System Diseases / diagnosis
  • Rheumatoid Factor / blood
  • Risk Assessment / methods*
  • Vasculitis / chemically induced
  • Vasculitis / diagnosis


  • Antirheumatic Agents
  • Isoxazoles
  • Rheumatoid Factor
  • Leflunomide