Leflunomide, an immunosuppressive drug with a relatively low adverse effect profile, is currently used to treat rheumatoid arthritis in humans. Leflunomide also appears to have antiherpesvirus properties: it has been used to successfully treat cytomegalovirus (CMV) in humans, and its active metabolite, A77, has been shown to inhibit replication of herpes simplex virus-1 and human CMV in vitro. In cats, renal allograft recipients often develop infection secondary to pharmacologic immunosuppression, and a large percentage of these cats develop severe respiratory tract disease. A study was performed to determine whether A77 would inhibit replication of feline herpesvirus-1 (FHV-1) in vitro. Feline kidney cell cultures were inoculated with FHV-1 and treated with concentrations of A77 ranging from 0 to 200 µM. The study found significant reduction in viral plaque numbers and viral load using concentrations of A77 > 20 µM. Complete suppression of plaque formation was noted with A77 concentrations > 100 µM. It was concluded that the antiherpesvirus activity might make leflunomide an alternative to currently used immunosuppressive protocols in feline organ transplant recipients.

COMMENTARY: While the basis for this study was the use of leflunomide in feline renal transplant protocols, the authors also note another potential use: treatment or prophylaxis for FHV-1 infections in cats unresponsive to conventional treatment and/or for use in susceptible populations (eg, shelters). This would be a vastly more far-reaching use for the drug and could have major clinical implications. The trick would be in determining whether the antiviral component can be identified and isolated from the general immunosuppressive effects. One hopes that this will be possible with further studies. -- Jennifer L. Schori, VMD

In vitro effects of the active metabolite of leflunomide, A77 1726, on feline herpesvirus-1. Williams CR, Sykes JE, Mehl M, et al. AM J VET RES 9:1010-1015, 2007.