What is the best DMT to start after taking Tysabri?

Question:
​My name is Steven and I was diagnosed with RRMS in 2005. I tried Copaxone, Rebif and for the last 3 and a half years Tysabri. I had to stop Tysabri because my JCV reading was 3.33 positive. After 2 weeks I did another blood test and the level dropped at 3.16 which is minimal however in the right direction. I had an MRI done and my neurologist told me to start Tecfidera immediately. I am very afraid to do so because it may exacerbate the JCV levels. Tecfidera has the same issues with PML as Tysabri. Should I risk it and start the therapy? I need a honest response. I am very hopeful for the new medication ocrelizumab so I can start it. My neurologist said that if ocrelizumab doesn't work for me, I need to wait 2 years until I start a new therapy. Please help!!!! Thank you very much!!!

Answer:
Steven, your questions reflect a some fundamental misunderstandings that are common among both MS patients and some providers, so let me take some time to explain.

1. Do any other disease modifying therapies have the same issue with PML that we see with Tysabri ?  The answer to this is absolutely no. There have been over 600 cases of PML with Tysabri and only rare, scattered reports of PML with other DMTs such as Tecfidera and Gilenya. Your risk of PML at present is about 1 in 100 or 1 %, whereas, we can not even calculate your risk on Tecfidera, because the risk is so low. There is also no known association between JCV antibody index values and risk of PML on Tecfidera or any DMT other than Tysabri. 
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More importantly, your risk of PML starts decreasing as soon as you stop Tysabri with a minimal risk of PML 3 months after stopping Tysabri,  as long as your MRI scan shows no evidence of early PML at the time you stop the tysabri.

2. What is the best DMT to start after stopping Tysabri? This is more complicated; a lot depends on your risk of relapsing in the 6 months after stopping Tysabri. If your risk is high (criteria include multiple enhancing lesions or multiple relapses in the year before started Tysabri), then Ocrelizumab is an excellent choice. If your risk is not particularly high, then both Tecfidera or Gilenya are good choices. You will need advise from your MS specialist on the best choice given your circumstances

3. What is the best time to start a new DMT after stopping Tysabri? This also depends on your risk of relapse after stopping tysabri. If your risk is considered low, wait 2-3 months and then obtain an MRI of the brain to make sure there is no evidence of early PML before starting a new DMT. If your risk of relapse is considered high, get a repeat MRI asap and start the new DMT asap, if the MRI shows no evidence of early presymptomatic PML

4. Do you need to wait 2 years after starting ocrelizumab to start another DMT?  We have little information on this subject at the current time. A lot depends on whether there is any significant evidence of immunosuppression when you stop the Ocrelizumab. We often use drugs like Ocrelizumab (so called anti CD20 agents) as an induction therapy (just the initial 2 doses) and then start another DMT immediately as maintenance therapy; so clearly many of us feel that this is a reasonable approach.

Revere (Rip) Kinkel MD
Professor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego