Which DMT is best for me?

Here is My Question:
I’ve been stable on Copaxone since my diagnosis about 5 years ago, my latest MRI a few weeks ago showed 2 new lesions. I then changed doctors after finding a practice that seems to treat the whole person and not just the condition, and as this has ramped up my anxiety it seems to be more of the type of care I need. This new doctor is a big believer in Tysabri extended interval dosing and seems to have much success with it (several hundred patients, majority 8+years, many with high JCV titers) and feels this would be the beet route, with Vumerity as a second option but not nearly as favored.

Since my diagnosis, from what I’ve read online in my panic-googling moments, Tysabri has always felt like the scariest option and when he named it my heart sank. Due to Covid vaccine concerns, he doesn’t suggest now is the time for Ocrevus or Kesimpta, which is what I was leaning towards.

I am JCV+ with a titer of 2.8 (when tested 4 years ago) and I’m terrified of PML. The new Dr, and again my panic-googling, show that the EID of Tysabri significantly reduces the risk, and the doctor said they would do bloodwork and MRIs every 3 months along with me reporting any issues as soon as I notice them. Does this then keep me in a safe place for moving forward with Tysabri or should I require more monitoring, or a different med altogether. So many have a PML risk.
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It seems to be a very effective med to help freeze any progression and maintain my quality of life. The studies I’ve read all seem to show greater increase risk if staying on the med for more than 2 years, and it seems to me it’s difficult to safely switch to another effective DMT after this one without triggering progression.
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I just don’t know how to know what’s best to make these decisions, any insight is greatly appreciated!

Answer:
So much information can be overwhelming to anyone, so let's take apart your question and answer it logically.

1. The overall risk of PML in Tysabri treated patients (300 mg IV every 28 days) with a JCV index > 1.5 is 1/1000 (a reasonable risk) during the first 2 years of treatment and then 1/100 (an unreasonable risk if other treatments are available) after 2 years of treatment. The risk in the first 12 to 18 months of treatment is much less than 1/1000.
2. Extended interval dosing does decrease the risk of PML substantially (> 90 %) but we do not specifically know the reduction of risk in those with a JCV index > 1.5, the highest risk group.
3. Anti-CD20 agents (Ocrevus, Rituximab and Kemsimpta) are excellent therapies for individuals who need to stop taking Tysabri because of the risk of PML. They are very effective at preventing rebound after stopping Tysabri.
4. Tysabri does not appear to affect your ability to mount a good response to vaccination . This has been demonstrated with the influenza vaccine. Anti-CD20 agents do appear to diminish vaccination responses.

With this information in mind, we often make the following recommendation to people with MS who need to switch to a more highly active disease modifying therapy.

1. It is okay to begin treatment with Tysabri even if your JCV index is > 1.5 if you monitor with MRI scans every 6 months during the first year of treatment. After 6 months to a year of treatment, you must switch to extended interval dosing or switch to an anti-CD20 therapy.
2. Get your COVID 19 vaccination during the time you are receiving Tysabri to protect you from COVID19.
3. Do not wait longer than 2 months to start anti-CD20 therapy after stopping Tysabri, but make sure you get an MRI of the brain after stopping Tysabri and before starting anti-CD20 therapy to make sure you do not have pre-symptomatic PML.

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Revere P (Rip) Kinkel, MDProfessor of Clinical Neurosciences
Director of the Multiple Sclerosis Program
Clinical Neurosciences Director
University of California San Diego