I was on Tysabri for 5.5 years until testing positive for JC antibodies. My neurologist took me off everything for three months so I could start Tecfidera, his concern being that he wanted me totally Tysabri-free before introducing another MS drug. During the detox my condition worsened. I've now been on Tecfidera for 25 months and my EDSS score has climbed from 5 to 6.5. My neurologist referred me to another neurologist with more experience with MS drugs and he gave me the option to remain on Tecfidera or go back on Tysabri. I should mention that while on Tysabri my condition remained largely unchanged--it's only since getting off that I've gone downhill.
The new doc says that at the October 2015 European MS conference there was a roundtable discussion where it came out that after two years off Tysabri the immune system resets itself with regard to Tysabri and PML risk. He thinks Tysabri is a viable alternative for me and, should I choose it, I will only need to detox from Tecfiera for 30 days. His thinking is to only be on Tysabri for two years or less given the promise of drugs in the development pipeline, though he did say we'll have to play it by ear. Unfortunately, there doesn't seem to be many numbers for someone that far out of Tysabri yet. So, I'd like to know more about the numbers before committing, however. That's where you come in.
I have a great deal of respect for how you seem to have your hands around the numbers, something I've never come across before. My neurologist has given me a script for blood work (to be taken in the next couple months) and it seems to make sense to have it taken at the end of my 30 day detox to get an accurate pre-Tysabri number rather than now. I'd like to go ahead with the Tysabri and would like to stop Tecfidera in the middle of January. I'd like to get an updated JC antibody titer then too. The only one I have is from 2.4 years ago.
Unfortunately, most of my cell counts from Labcorp are only displayed as a number within a reference range or percentages. There aren't any absolute numbers of CD8 cells like other people have reported. Hell, I don't see CD8 cells listed. Is it possible to convert my numbers to what other people report? Wait, my absolute lymphocytes are 1100 and lymphocytes are 17%, and both are listed as within the normal range.
So, my questions to you are 1) what do I have to ask Labcorp for to get the numbers everyone else seems to be using? 2) When I get a JC anitbody titer in February, what number should I hope for to feel good about my odds back on Tysabri?, and 3) what do you think about someone with my history going back on Tysabri?
You’ve asked some very good questions, so let’s see if I can answer each one.
1. I am not aware of any cases of PML starting more than 6 months after stopping Tysabri. Those who develop PML during this interval likely had asymptomatic PML, even before the Tysabri is stopped. Therefore, it does not take anything close to 2 years to “reset” the immune system after stopping Tysabri. This process occurs within 3-6 months of stopping Tysabri.
2. The problem with stopping Tysabri and waiting several months before starting another DMT is the high risk of MS relapse within 3 to 6 months of stopping Tysabri, as you found out the hard way. For this reason, most MS specialist do NOT use a “wash out” period in any patient switching from Tysabri to another DMT. I do obtain an MRI before stopping Tysabri to evaluate for possible PML. If the MRI shows new T2 hyperintensities, especially those associated with Diffusion weighted Trace image signal, I make sure there is no evidence of PML before restarting either Tysabri or another DMT.
3. For those patients who are great candidates for Tysabri and responding well to treatment, many of us increase the interval between Tysabri infusions to every 2 months (56 days) if the patient becomes JCV antibody positive 12 months or greater after starting treatment. This is particular true of older (> 50) and thinner (less than 60 kg) patients. We then usually monitor for PML with brief MR scans every 4 months (a 7 minute scan with FLAIR and DWI trace images only without gadolinium). There is increasing evidence that dosing Tysabri in this manner dramatically reduces the risk of PML.
4.For patients on tecfidera with normal lymphocyte counts (like yourself), I see no reason to wait a month before starting another DMT. Remember, the only known risk factor for PML in Tecfidera treated patients is an absolute lymphocyte count less than 600. I would simply obtain an MRI of the brain before stopping Tecfidera to make sure everything is stable. In your case, Tysabri is a reasonable choice. I would restart on monthly Tysabri infusions with repeat MRI of the brain every 6 months. The infusions should be extended to every 2 months (56 days) after 12 infusions with more frequent MR imaging of the brain. Alternatively, your MD could consider treatment with Ocrelizumab when this becomes available. This will hopefully occur by the end of 2016
Revere (Rip) Kinkel MD
Director of the Multiple Sclerosis Program
Professor of Clinical Neurosciences
University of California San Diego