Peripheral neuropathy in patients treated with leflunomide.
OBJECTIVE
Our objective was to describe the clinical features, time course, and outcome of new-onset peripheral neuropathy occurring in patients treated with leflunomide.


METHODS
Case reports of peripheral neuropathy submitted to the US Food and Drug Administration in association with leflunomide use were reviewed. Data on patient demographics, underlying medical conditions and medications, details of leflunomide therapy, and treatment and outcome of the neuropathy event were abstracted. Time to neuropathy onset and time to improvement or recovery were analyzed by survival analysis.


RESULTS
Of 80 reported patients, 61% were women. The patients' mean age was 62 years. Symptoms of peripheral neuropathy began after a mean of 6 months of leflunomide use (range, 3 days to 3 years). Electrodiagnostic testing in 37 patients was consistent with a distal axonal, sensory, or sensorimotor polyneuropathy in most patients. Patients who stopped leflunomide use within 30 days of neuropathy symptom onset were more likely to have improvement or recovery than those who continued taking leflunomide for a longer period (P <.001).


CONCLUSIONS
Leflunomide use is associated with peripheral neuropathy in some patients. This neuropathy is usually axonal in nature, affecting multiple sensory or motor nerves of distal extremities. Patients who stopped leflunomide use within 30 days of symptom onset were more likely to have improvement of symptoms or complete recovery than were patients who continued to use the drug for longer periods of time.
Bonnel
Renan A
RA
Office of Drug Safety, Center for Drug Evaluation and Research, US Food and Drug Administration, Rockville, MD 20857, USA. bonnelr@cder.fda.gov
Graham
David J
DJ
D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D000368:Aged; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000009:adverse effects*; D000077339:Leflunomide; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000453:epidemiology; D016016:Proportional Hazards Models; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration / Q000706:statistics & numerical data*
D007555:Isoxazoles; D000077339:Leflunomide