A list of questions from a neurologist on how to deal with lymphopaenia and MS DMTs that I try to answer. They are all very interesting and challenging.
Lots of mind blowers in this one! I didn't realize the PML carryover risk from Natalizumab was well understood, among others.
So my question: I am on fingolimod and get 6-monthly labs and my doc says they are in a healthy range. But seeking COVID data on fingolimod, there have been a few papers where patients are split out by their lymphoctye counts, and I have discovered (I think) that mine are on the lower end of expected-with-fingolimod. Does this mean anything? (just being low-even-for-fingolimod, not my particular value) Is it suspected to mean anything? Or just interpersonal variation?
I also wonder about the 'cumulative' risk of lymphopaenia when switching from one DMT to another - or, in my case, on my 4th DMT. After severe prolonged lymphopaenia on my 3rd DMT, I decided to quit DMTs for 8 months, and let my ALC recover, before starting my 4th DMT. I know that's a risk, but I think starting a new DMT when your ALC (and CD8 T) is still very low, is also risky... I would be interested to know if there is literature/data/guidelines on this topic.
Yes, there is data on each DMT. Interferon-beta, S1P modulators, fumarates, teriflunomide, alemtuzumab, mitoxantrone, anti-CD20 therapies, cladribine, HSCT and steroids all cause lymphopaenia to a greater or lesser extent and it may persist to a greater and lesser extent. The only agents that don't are glatiramer acetate and natalizumab. This is why DMT-specific knowledge is essential as some of these DMTs have carry-over effects. I will be dealing with this issue when I discuss each DMT in turn.
Re: "Do you have an opinion on the FLCCC protocols- especially prevention or early treatment guidelines?"
I can't comment without going through them in detail, which I don't have the time for. I note that they promote ivermectin, which has been shown not to work and is not recommended by the WHO, MHRA, NICE, NHS, etc. In fact, ivermectin may cause more harm than good. We now have licensed alternatives that have been shown to work.
Lots of mind blowers in this one! I didn't realize the PML carryover risk from Natalizumab was well understood, among others.
So my question: I am on fingolimod and get 6-monthly labs and my doc says they are in a healthy range. But seeking COVID data on fingolimod, there have been a few papers where patients are split out by their lymphoctye counts, and I have discovered (I think) that mine are on the lower end of expected-with-fingolimod. Does this mean anything? (just being low-even-for-fingolimod, not my particular value) Is it suspected to mean anything? Or just interpersonal variation?
Is there reliable data on the persistence of lymphopaenia after discontinuation of the various DMTs?
I refer to e.g. https://journals.sagepub.com/doi/abs/10.1177/1352458520988149 - a lot of the DMTs discussed are relatively recent, or in any case more recent than DMF.
I also wonder about the 'cumulative' risk of lymphopaenia when switching from one DMT to another - or, in my case, on my 4th DMT. After severe prolonged lymphopaenia on my 3rd DMT, I decided to quit DMTs for 8 months, and let my ALC recover, before starting my 4th DMT. I know that's a risk, but I think starting a new DMT when your ALC (and CD8 T) is still very low, is also risky... I would be interested to know if there is literature/data/guidelines on this topic.
Yes, there is data on each DMT. Interferon-beta, S1P modulators, fumarates, teriflunomide, alemtuzumab, mitoxantrone, anti-CD20 therapies, cladribine, HSCT and steroids all cause lymphopaenia to a greater or lesser extent and it may persist to a greater and lesser extent. The only agents that don't are glatiramer acetate and natalizumab. This is why DMT-specific knowledge is essential as some of these DMTs have carry-over effects. I will be dealing with this issue when I discuss each DMT in turn.
I didn’t realize that DMTs could imprint on the immune system! All so complicated, and if you don’t have an MS specialist…
Off topic: How do you pose a query to the substack?
My queries:
Do patients on Anti-CD20 or Fingolimod mount a durable immune memory to SARS-Cov-2 disease (not vaccinated) while on treatment?
For patients using Rituximab long term do they have a better chance to create memory cells closer to (or slightly past) their 6 month reinfusion date?
Do you have an opinion on the FLCCC protocols- especially prevention or early treatment guidelines?
Much appreciated,
Felicity
Re: "Do you have an opinion on the FLCCC protocols- especially prevention or early treatment guidelines?"
I can't comment without going through them in detail, which I don't have the time for. I note that they promote ivermectin, which has been shown not to work and is not recommended by the WHO, MHRA, NICE, NHS, etc. In fact, ivermectin may cause more harm than good. We now have licensed alternatives that have been shown to work.
Re: Do patients on Anti-CD20 or Fingolimod mount a durable immune memory to SARS-Cov-2 disease (not vaccinated) while on treatment?
https://gavingiovannoni.substack.com/p/ronapreve-prophylaxis-vs-therapeutic
https://gavingiovannoni.substack.com/p/case-study-ocrelizumab-and-covid
https://gavingiovannoni.substack.com/p/ocrelizumab-and-the-3rd-dose-of-the
https://gavingiovannoni.substack.com/p/case-study-covid-19-vaccine-choice
https://gavingiovannoni.substack.com/p/anti-cd20-kool-aid-and-covid-19-vaccines