Neuropathy in multiple sclerosis patients treated with teriflunomide

Teriflunomide is an oral medication approved for the treatment of patients with multiple sclerosis. The primary effect of teriflunomide is to reduce de novo pyrimidine synthesis by inhibiting mitochondrial dihydroorotate dehydrogenase, thereby causing cell-cycle arrest. We aimed to investigate the occurrence of peripheral neuropathy, a rare side effect of teriflunomide, in patients receiving teriflunomide.

Multiple sclerosis patients receiving teriflunomide (n=42) or other disease modifying therapies (n=18) and healthy controls (n=25) were enrolled in this cross-sectional study between January 2020 and 2021. The mean duration of teriflunomide treatment was 26 months (ranging from 6 to 54 months). All participants underwent neurological examination and nerve conduction studies of tibial, peroneal, sural, superficial peroneal, median, and ulnar nerves by using surface recording bar and bipolar stimulating electrodes.

The mean superficial peroneal nerve distal latency and conduction velocity were significantly slower, and the mean superficial peroneal nerve action potential amplitude was lower in patients using teriflunomide (2.50 ms, p<0.001; 47.35 m/s, p=0.030; and 11.05 μV, p<0.001, respectively). The mean peroneal motor nerve distal latency was significantly longer and amplitude was lower in teriflunomide patients (3.68 ms, p<0.001, and 5.25 mV, p=0.009, respectively). During the study period, treatment switching to another disease-modifying therapy was planned in 10 patients, and all neuropathic complaints were reversed after switching.

Teriflunomide has the potential to cause peripheral neuropathy. The awareness of peripheral neuropathy, questioning the symptoms, and if suspected, evaluation with electromyography and switching the therapy in patients under teriflunomide treatment are crucial.