Will any DMT stop my disability progression?

Here is My Question:
My question requires some background information. I am a 46 year old female diagnosed in 1999 when I was 31 years old. My 1st documented symptom happened in '94. 

I have tried the following treatments: Copaxone '99-'04, Rebif '04-'06, Cytoxan while on Rebif in '06, Tysabri '07-'08 straight onto Rituxan in '08-'10. Just after Rituxan I had 8 weeks of Plasmapheresis followed by 2 years of monthly IVIG & Steroids only '11-'13. 

All of these treatments were stopped due to antibodies and/or continual progression/ineffective response. In 2013 I decided to go back to Copaxone which I stayed on until an MRI showed active lesions in April '14 (my 1st mri to show 'active' lesions in all this time). I started Tecfidera in July '14 & had further progression which prompted me to stop it in Nov '14 just as Lemtrada became approved in the US. 

My neurologist advised a drug holiday while waiting for Lemtrada certification. With no idea when certification may come & 5 months of no treatment I decided to try Aubagio while waiting, which I am in my 3rd week of now. I am now considered Relapsing-Progressive, am in a scooter full time, cannot take a step, stand up straight or raise my arms above my head. Since Tecfidera I am losing the use of my right hand. I believe my EDSS is 8-8 1/2. 

I have two questions:
1. When Lemtrada does become available to me, having had no positive result from Chemo, Tysabri or Rituxan, is its mechanism of action likely to have an effect on my particular MS case? If so do I have any hope of it stopping my progression being at the stage that I am?
2. And if not Lemtrada is Aubagio the right DMD to try at this point. 

Thanks for your time!

Answer:
I'm sorry to hear of your experience with the various DMTs.  As physicians, we try out best to match up an individual patient's form of MS to the "right" DMT.  However, we do not have a biomarker (ie, a blood test) that can tell us exactly where the trouble is in the immune system (for a given patient) so we could more readily match that immune dysregulation to a DMT with a specific and complimentary mechanism of action.  It really is a "trial and error" process.  What's more, there is the possibility that an individual with MS may have a disease course that will not be stopped or significantly altered by any of our currently available DMTs. 

From what little I know about your case (and this opinion cannot substitute for the opinion of your specialist who knows you), you appear to have persistent inflammatory disease activity (particularly given the new MRI activity you mention).  This signals to me that there is still a chance that a DMT could be helpful in your situation.  Lemtrada is the newest DMT approved for use.  It is very effective (when looking at the data from the pivotal clinical trials) in reducing inflammatory disease activity.  However, it does come with a significant (potential) downside--autoimmunity.  Specifically, there is a greater risk of developing a condition where your immune system could start attacking your platelets (causing serious bleeding), kidneys, and thyroid.  These tend to be treatable conditions, but they are not insignificant.  Whenever considering a DMT, you and your physician must weigh the pros/cons.  We do not expect that our DMTs will reverse already accumulated disability, but they may mitigate further progression (at least in the short term... ie, a couple years).  This is something that would need to be considered in your case.  

These are not easy decisions, and I think it comes down to what your goals are and the level of risk you are willing to assume.

I hope this helps.

A. Scott Nielsen MD MMSc
Virginia Mason Multiple Sclerosis Center