Is teriflunomide the tortoise of the DMT world? #MENACTRIMS2016 #MSBlog #ClinicSpeak
“In my second talk at MENACTRIMS I was asked to define a suboptimal responder to DMTs. As you can see many of my slides are old; yawn! I focused a large section of my talk on sequencing of DMTs. In relation to this, there is one slide that I highlighted in particular; slide 23 on the pooled analysis of the teriflunomide phase 3 trials (TEMSO & TOWER). It shows teriflunomide bucking the trend; surprisingly teriflunomide is more effective on both relapse, and disability, outcomes in pwMS who have failed, or had a suboptimal response, to previous DMTs (mainly IFNbeta and GA). Why? I have no idea. This data clearly differentiates teriflunomide from the other orals and even the monoclonal antibodies (natalizumab & alemtuzumab). The mechanisms driving disease activity and progression in established disease are complex. Some of them occur in the periphery and others within the central nervous system. Could teriflunomide be working on both peripheral and central mechanisms? It would be fascinating to find out if pwMS going onto teriflunomide alter their CSF profiles, in particular in relation to intrathecal B and plasma cell biology.”
“Up until now I haven’t paid much attention to teriflunomide simpling lumping it with the other platform therapies; however, this data changes my perceptions of the drug. I would like to know the biology behind these numbers. If there is biology teriflunomide may be a good drug post induction therapy to target the progressive pathology of MS. Several of us in the field have been pushing for a clinical trial of teriflunomide post alemtuzumab; the aim of this study would be to see if teriflunomide could prevent secondary autoimmunity. I beginning to think we should start this trial ASAP and also power it for efficacy. Could teriflunomide prevent the need for a third, fourth or fifth course of alemtuzumab? Could teriflunomide result in the loss of oligoclonal IgG bands in the CSF. Just maybe we have found a drug that targets plasma cell biology. Come to think of it why not do this study in progressive MS? Progressive MS is where there is the greatest unmet need.”
“In my second talk at MENACTRIMS I was asked to define a suboptimal responder to DMTs. As you can see many of my slides are old; yawn! I focused a large section of my talk on sequencing of DMTs. In relation to this, there is one slide that I highlighted in particular; slide 23 on the pooled analysis of the teriflunomide phase 3 trials (TEMSO & TOWER). It shows teriflunomide bucking the trend; surprisingly teriflunomide is more effective on both relapse, and disability, outcomes in pwMS who have failed, or had a suboptimal response, to previous DMTs (mainly IFNbeta and GA). Why? I have no idea. This data clearly differentiates teriflunomide from the other orals and even the monoclonal antibodies (natalizumab & alemtuzumab). The mechanisms driving disease activity and progression in established disease are complex. Some of them occur in the periphery and others within the central nervous system. Could teriflunomide be working on both peripheral and central mechanisms? It would be fascinating to find out if pwMS going onto teriflunomide alter their CSF profiles, in particular in relation to intrathecal B and plasma cell biology.”
“Up until now I haven’t paid much attention to teriflunomide simpling lumping it with the other platform therapies; however, this data changes my perceptions of the drug. I would like to know the biology behind these numbers. If there is biology teriflunomide may be a good drug post induction therapy to target the progressive pathology of MS. Several of us in the field have been pushing for a clinical trial of teriflunomide post alemtuzumab; the aim of this study would be to see if teriflunomide could prevent secondary autoimmunity. I beginning to think we should start this trial ASAP and also power it for efficacy. Could teriflunomide prevent the need for a third, fourth or fifth course of alemtuzumab? Could teriflunomide result in the loss of oligoclonal IgG bands in the CSF. Just maybe we have found a drug that targets plasma cell biology. Come to think of it why not do this study in progressive MS? Progressive MS is where there is the greatest unmet need.”
“Could teriflunomide be the equivalent of the tortoise in Aesop’s fable ‘The Tortoise and the Hare‘?
Why don't you look at the stats of this prof g? Where are the confidence intervals in these graphs. The numbers in the prior DMTs are lower; I bet this is just statistical noise.
What about cambridge trial with alemtuzumab + low dose rituximab? is anywere close to ending? The fact it hasnt been terminated to this day makes me think they found something.Now teriflunomide being such a safe drug, i think its worth the try to go for this, maybe will get us closer to understanding the progressive phase.What about alemtuzumab + laquinimod or BG12? This maybe makes more sense for RR, deplete and then try to get what we think are neuroprotective agents, maybe even get more atrophy reducction —> disability reducction.Sorry if my english its a bit rusty D:
I think you are mistaken, alEM + rituximab is a study that should be done.The trial at Cambridge is Thy-CAM apparently due to finish October 2017, they are trying to boost thymic output..emTeriflunomide a safe drug, each one has side effects.Alemtuzumab and teriflunomide both genzyme laquinimod is teva so less likely to happen
I think you are mistaken, alEM + rituximab is a study that should be done.The trial at Cambridge is Thy-CAM apparently due to finish October 2017, they are trying to boost thymic output..emTeriflunomide a safe drug, each one has side effects.Alemtuzumab and teriflunomide both genzyme laquinimod is teva so less likely to happen
How does teriflunomide work? What's the proposed mechanism?
Teriflunomide is an immunomodulatory drug inhibiting pyrimidine de novo synthesis by blocking the enzyme dihydroorotate dehydrogenase. ITeriflunomide inhibits rapidly dividing cells, including activated T cells, which are thought to drive the disease process in MS. Teriflunomide may decrease the risk of infections compared to chemotherapy-like drugs because of its more-limited effects on the immune system.It has been found that teriflunomide blocks the transcription factor NF-κB. (Wikipaedia). There were some ineresting posters at ECTRIMSthe data should surface soon
As always such excellent thoughtful questions from both the prof and the commenters and so few answers. I hate reading books with unwritten endings. I know life is a book with an unwritten ending but at least I hold the pen to the life book. Thank you for sharing the presentations, really peaked my interest. Bojana
Perhaps this patients' neurologist is on to something?http://www.mslisasays.com/treatment-2/update-on-my-new-treatment-aubagio/I've followed this blog for a while, which details a patient (the blogger) who initially responded well to Alemtuzumab. After a few courses it stopped working, but according to the blogger, starting Aubagio really helped.
The last update the blogger made for the Aubagio switch was March 2015.