Teriflunomide is the dark-horse of the MS DMTs. The clinical development programme took much longer than other DMTs and when it arrived it was launched into a crowed environment. However, the more Teriflunomide is used the more we learn and get surprised about its utility.
What differentiates Teriflunomide from the other DMTs is that it is more effective when used 2nd or 3rd line. Why? It is not a immunosuppressive agent, i.e. the lymphopaenia is mild, it is not associated with opportunistic infections, it does not blunt vaccine responses and is not at present associated with a secondary malignancy signal. Teriflunomide is the only licensed oral DMT to have shown an impact on disability progression in both phase 3 pivotal trials. It also seems to become more effective with time. The biggest surprise to me was the finding that Teriflunomide has anti-viral effects across a range of viruses. Could Teriflunomide’s anti-viral mode of action be responsible for its profile? Could be working via suppressing EBV?
The paper below describes the use of Teriflunomide in a real-world setting and confirms that its profile is similar to that has been described in the phase 3 programme. So why are we not using Teriflunomide more in clinical practice? It relates to the EMA label that requires us to monitor the liver function and full blood counts every 2 weeks for 6 months and then 2-monthly after that. These requirements are a legacy of the Leflunomide EU label and are different from the FDA label. I have therefore asked whether or not the phase 3 data can be interrogated to see if 2-weekly blood monitoring in the first 6-months makes the drug safer than 4-weekly monitoring. Surely pharmacovigilance monitoring should be evidence-based? If we show that patient safety is not compromised by 4-weekly monitoring then more of our patients would choose Teriflunomide over other agents.
CoI: multiple
It is anti viral. Where is the evidence profG.If it is such a good anti-viral why were the results of phase 3 not more impressive, where it is considered a low efficacy DMT. Is this wrong or does it question the viral idea?
There an actrim poster by Keith Edwardsand evidence from leflunomide. Teriflunomide is anti proliferative I guess viral replication uses building blocks affected by TeriI'll have to do homework or maybe profG can do one.
Thank you for the post as always…. I think this is the actrims poster if people want to follow up: http://msneny.org/wp-content/uploads/2016/06/Teri-ACTRIMS-2017-Antivirals-Poster_Final.pdf
Why not just give anti viral drugs to MS patients? Such as the one used in HIV? Surely this would prove once and for all the EBV hypothesis. Besides HIV is really good at hiding and much more virulent then EBV. Just seems all the research is going around in circles. Or try combination therapies? Tecfidera with aubogii? Alemtuzumab with fingolimod? 2nd one will control the 2nd autoimmunity?
No such thing as a new idea ;-)http://multiple-sclerosis-research.blogspot.com/2015/03/crowdspeak-what-has-happened-to-charcot.html
Can people with hiv get ms? If so doesn't this disprove Everything? Just being devil's advocate.
Lower risk. More below. Open access. Team G.http://jnnp.bmj.com/content/86/1/9
This story implies hiv drug helps ms. Lady with both saw an improvement.http://www.bbc.co.uk/news/av/uk-england-sussex-34660848/ms-patient-walks-after-taking-hiv-drugs
We are in the process of summarising the profile of Teriflunomide as an antiviral drug as a review article.