Questions About Tecfidera And Tysabri And PML Risk

Question:
Hello, My neurologist has been encouraging me to go on Tecfidera for a little while now, and I recently became willing to do so until my jc virus test came back positive with a score of 0.78. Now, I can't even get my neurologist to address this with me over the phone, so I am going to discuss the results with him at an appointment in a few days. He did relay to me, however, through his assistant, that he considers my score on the JC virus test low enough to not be a concern. But among the questions I have are the following:

1. Is there a consensus in the neurological community about what score indicates a substantial risk for PML with Tecfidera? I have read a rather detailed set of statistics for PML and Tysabri, but I have not been able to uncover the same data for Tecfidera.

2. Is there really a firm scientific basis for concluding that "there is no real risk" of PML associated with Tecfidera" (which I know is what many neurologists are likely to say.)

​I have read a couple of articles indicating that the actual number of cases of PML may be higher than the officially recognized number of 5 (or whatever it is currently). I have read many, many accounts from folks whose neurologists didn't even do ANY preliminary testing prior to the administration of Tecfidera of Tysabri, It is difficult for me to trust that in such cases the level of patient reporting and follow-up is necessarily reliable and/or consistent. All of which is compounded by the fact that PML symptoms mimic MS symptoms. I guess what I am getting at is that it is difficult for me to just trust that I am fine even given a positive JC virus test, given the relatively short track record of this particular drug, as well as some of the other factors that I mentioned. If anyone can present some evidence or insight into this issue it would be greatly appreciated. Thank you!

Answer:
The number of cases of PML in people taking Tecfidera is far too low to create a risk stratification based on JCV index or any other factors at present.  This is why no one currently recommends using the JCV index test to determine if a person should take Tecfidera. It is not a question of belief, it is a question of data.

Let me give you an example. We know that at least 50 % of adults are JCV antibody positive. Assume the overall risk of PML on Tecfidera is 1 in 25,000 (a conservative estimate). If only the JCV antibody positive patients are at risk for PML (which is 50 % of the people on tecfidera for this example) then the risk in these patients would still be only 1 in 12,500. Other factors could increase this risk, such as the development of a low lymphocyte count while taking Tecfidera, but the risk would still be very low and no where near the 1 in 100 risk of developing PML in JCV antibody positive people with prior chemotherapy treatment who receive Tysabri for more than 2 years.

Remember risk is always relative to what you are trying to prevent with a treatment. In many people with MS the risk of disability over any 5 year period is far higher than 1 in 100

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