With regard to Teriflunomide, there is an increasing number of reports of how well pwMS are doing on teriflunomide long-term. Teriflunomide is the only DMT that works significantly better second, or third, line than it does as a first-line treatment (see figure below). I have hypothesised that these observations may be due to teriflunomide's mode of action as an anti-viral agent. Professor Julian Gold and I are in the process of exploring this hypothesis under the umbrella of the Charcot Project. We will let you know as soon as we have data available.
Josephson et al. Treatment of renal allograft polyoma BK virus infection with leflunomide. Transplantation. 2006 Mar 15;81(5):704-10.
BACKGROUND: Polyoma BK virus produces an aggressively destructive nephropathy in approximately 3% to 8% of renal allografts, is associated with graft loss within one year in 35% to 67% of those infected and there is no therapy of proven efficacy. Leflunomide is an immune suppressive drug with anti viral activity in vitro and in animals.
METHODS: We treated twenty-six patients with biopsy proven NK virus nephropathy (BKN) with either leflunomide alone (n=17) or leflunomide plus a course of cidofovir (n=9) and followed them for six to forty months. Leflunomide was dosed to a targeted blood level of active metabolite, A77 1726, of 50 microg/ml to 100 microg/ml (150 microM to 300 microM). Response to treatment was gauged by serial determinations of viral load in blood and urine (PCR), serum creatinine, and repeat allograft biopsy.
RESULTS: In the 22 patients consistently sustaining the targeted blood levels of active drug, blood and urine viral load levels uniformly decreased over time (P<.001). Mean serum creatinine levels stabilized over the first six months of treatment, and with 12 months or more of follow-up in 16 patients the mean serum creatinine has not changed significantly from base line. Four patients who did not consistently have blood levels of active drug (A77 1726) above 40 microg/ml did not clear the virus until these levels were attained or cidofovir was added.
CONCLUSIONS: Leflunomide inhibits Polyoma virus replication in vitro and closely monitored leflunomide therapy with specifically targeted blood levels appears to be a safe and effective treatment for Polyoma BK nephropathy.
Morita et al. Successful low-dose leflunomide treatment for ganciclovir-resistant cytomegalovirus infection with high-level antigenemia in a kidney transplant: A case report and literature review. J Clin Virol. 2016 Sep;82:133-8. doi: 10.1016/j.jcv.2016.07.015.
Ganciclovir-resistant cytomegalovirus infection is sometimes life-threatening for organ transplant recipients. Foscarnet is an alternative, although it may potentially worsen the preexistent impaired renal function. Here we report the case of a successful low-dose leflunomidetreatment in a kidney transplant recipient with very high viral replication, who underwent kidney transplantation 10 years before. Administering 10mg leflunomide daily for 5 months without a loading dose completely cleared the ganciclovir-resistant cytomegalovirus strains.