ClinicSpeak: defining suboptimal responders

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."



"Could teriflunomide be the equivalent of the tortoise in Aesop's fable 'The Tortoise and the Hare'?


Defining suboptimal response to treatment in ms menactrims 2016 from Gavin Giovannoni

CoI: multiple

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