The investigators analyzed data from the German RABBIT (Rheumatoid Arthritis Observation of Biologic Therapy) registry, an ongoing prospective cohort study started in 2001. Over 250 rheumatologists have contributed information on RA patients, including those who take an anti-tumor necrosis factor drugs and those starting monotherapy with a traditional disease-modifying antirheumatic drug or combination therapy undertaken after failing to response to at least one DMARD.

The analysis presented by Dr. Anja Strangfeld at the annual meeting of the American College of Rheumatology included 5,017 registry patients: 3,246 on a TNF blocker and 1,771 on a DMARD. Among the registrants, there were 22 new cases of peripheral neuropathy and 53 cases of probable peripheral neuropathy.

While 27% of the registry patients were treated with leflunomide, 14 (64%) of the patients with peripheral neuropathy and 17 (33%) of patients with symptoms were treated with leflunomide.

The incidence rates for confirmed peripheral neuropathy were 5.2 per 1,000 person-years for leflunomide, 1.4 per 1,000 for methotrexate, and 0.9 per 1,000 for the anti-TNFs. Incidence rates for symptoms of peripheral neuropathy were 6.7, 3.8, and 4.3 per 1,000 person-years for leflunomide, methotrexate, and TNF blockers, respectively.

Findings from a multivariant Cox regression analysis showed that treatment with leflunomide increased the risk for peripheral neuropathy 4.27-fold. Sjögren's syndrome was even more strongly associated with the disorder, increasing the risk 6.77-fold. Neither methotrexate nor TNF blockers were linked to the increased risk for peripheral neuropathy.

Of the 14 patients on leflunomide who had frank peripheral neuropathy, 11 discontinued. Within 4 months of stopping therapy, three had recovered and four were improving. Of the three patients who continued therapy, one improved. Two have ongoing peripheral neuropathy. Three of the patients who recovered after stopping leflunomide restarted; one relapsed after 9 months; two stopped for unrelated reasons.

Of the 53 patients with peripheral neuropathy symptoms, 18 discontinued and 15 of those recovered. The median time on leflunomide in this group was 5.5 months, said Dr. Strangfeld of the German Rheumatism Research Center Berlin. Two patients were found to have diabetes.