Novartis announced yesterday that an MSer treated with fingolimod had
been diagnosed with PML. Importantly the MSer concerned had
previously been treated with natalizumab.
been diagnosed with PML. Importantly the MSer concerned had
previously been treated with natalizumab.
As you are aware natalizumab is strongly associated with PML. Therefore it
is difficult to point a finger at, or blame, fingolimod as the cause of the PML in this specific case.
However, fingolimod is likely to have contributed to the problem. This is
why it is essential for neurologists to make sure that the risk of PML
carry-over, when swicthing from natalizumab to fingolimod, is minimised. This
is why we, at the Royal London Hospital, stop natalizumab for at least 3
months, and do a lumbar puncture, and MRI scan to make sure that there is no
sub-clinical evidence of PML, before starting fingolimod. We think there is a asymptomatic period of several months before PML causes symptoms and presents clinically. The problem with
fingolimod is that once it is your system it takes a long time for it wash-out
after stopping the drug; weeks to months. Therefore if you develop PML on
fingolimod it will take months for your immune system to reconstitute to a
level were it can fight the JC virus that causes PML and hopefully allow you to
recover from the infection. Unfortunately, many of us predicted this
complication and have been speaking about it for sometime. This case is
unlikely to be the last case of PML in MSers on fingolimod. We need to be
vigilant and limit the risk as much as possible.
Source: Marta Falconi. Novartis
Gilenya Patient Gets Rare Brain Disease. Wall Street Journal. April 13, 2012,
9:17 a.m. ET.
is difficult to point a finger at, or blame, fingolimod as the cause of the PML in this specific case.
However, fingolimod is likely to have contributed to the problem. This is
why it is essential for neurologists to make sure that the risk of PML
carry-over, when swicthing from natalizumab to fingolimod, is minimised. This
is why we, at the Royal London Hospital, stop natalizumab for at least 3
months, and do a lumbar puncture, and MRI scan to make sure that there is no
sub-clinical evidence of PML, before starting fingolimod. We think there is a asymptomatic period of several months before PML causes symptoms and presents clinically. The problem with
fingolimod is that once it is your system it takes a long time for it wash-out
after stopping the drug; weeks to months. Therefore if you develop PML on
fingolimod it will take months for your immune system to reconstitute to a
level were it can fight the JC virus that causes PML and hopefully allow you to
recover from the infection. Unfortunately, many of us predicted this
complication and have been speaking about it for sometime. This case is
unlikely to be the last case of PML in MSers on fingolimod. We need to be
vigilant and limit the risk as much as possible.
Source: Marta Falconi. Novartis
Gilenya Patient Gets Rare Brain Disease. Wall Street Journal. April 13, 2012,
9:17 a.m. ET.
Do you think that prior use of fingolimod is likely to increase the risk of PML if someone goes on Tysabri later?
Re: "Do you think that prior use of fingolimod is likely to increase the risk of PML if someone goes on Tysabri later?"Yes, almost certainly. Fingolimod is an immunosuppressive agent therefore it will need to be included as part of the high-risk agents.
I am very curious about the timing of this case. How long was this person taking fingolimod before developing PML? 1 month? 1 year? How much time was given as a wash-out period between stopping natalizumab and beginning fingolimod? 0 days? 30 days? 90 days?
Dr. Giovannoni, are there active studies investigating risk profiles for patients who stop natalizumab and begin to take the newer medications?As the armamentarium of pharmaceuticals increases, so does the complexity of choosing between meds based on both efficacy and risks/side effect profile. Add in the interplay between medications and the waters begin to muddy very quickly.I have a very personal stake in this as I am currently on natalizumab dose #2 due to failure of GA therapy. I feel definite improvement, but I am also JCV positive (no prior immunosuppressant use), so I will be looking to jump to another med prior to the 2 year mark. I am nervous about the (controversial) rebound effect after stopping natalizumab as well as additive risks of other meds. Currently I am keeping my fingers crossed for BG-12. My dream med is really alemtuzumab (thyroid issues and ITP be damned!), but I wonder if there would be any theoretical reason at all to stop natalizumab for fear of PML only to go onto another (very powerful) monoclonal. At least natalizumab can be pulled out of the system.Anyway, it would be so comforting to see some type of data following patients as they move on from natalizumab to other therapies.
Re: "Anyway, it would be so comforting to see some type of data following patients as they move on from natalizumab to other therapies."Unfortunately, it is too early to have data of this kind. This will come slowly from national registers. Unfortunately, we have not been able to get a UK register off the ground. The reasons for the latter are very frustrating.
Re: "I am very curious about the timing of this case. How long was this person taking fingolimod before developing PML? 1 month? 1 year? How much time was given as a wash-out period between stopping natalizumab and beginning fingolimod? 0 days? 30 days? 90 days?"As soon as I have more information I will post it on the blog!
I don't think there have been any cases of PML with alemtuzumab (so far). My son had a lumbar puncture and MRI to check anyway he was JCV negative before he had it. I think the actual drug alemtuzumab disappears out of the body within a matter of weeks?months? although it's effects last for years. As it's only generally given in 2 bursts a year apart it is not the same as infusing a drug month after month so that the body is never without natalizumab, I think.
Anon 4.55 is correct
Re: Anon 4:55 is correct in relation to MS. There have been several cases in people treated with Alemtuzumab for oncological indications.