BartsMS Filmweek Part 5

B

Part 5

Oral Cladribine and IRT

CoI: These videos were sponsored by Merck and for regulatory purposes this has to be disclosed. However, this was collaborative and the content was generated by a video production company following generation of a story board created by them and importantly ProfK and B and BartsMS PPI members acting as consultants via Queen Mary University of London.

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MouseDoctor

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  • I loved watching the 5 part video. I like how it was chunked up in smaller pieces. However, I soon learned that my silly MS forgetful memory had to go back with my questions & watch all 5 again in succession. I do have a question though ⁉️ This ends saying that the patient was relapse free. But what about those who never experience relapses, or the relapses are barely noticeable until they’ve successfully caused a fair amount of further disability? And, what if a person has already been on other meds such as Ocrevus and levels if absolute lymphocytes are still at an all time low & not reconstituting? (Last treatment a year ago). And because of other health issues that prevents them from other meds. Also, what are side effects of clabridine that can be exasperated by previous meds already taken?

    • Bit of positive spin there at the end that there was no further relapse, and whilst this is evidence based, is obviously somewhat dependent on duration of follow up. The issue of disability accrual is not resolved. Whilst the new measure “PIRA” (progression without relapse activity) suggests most of it happens “between” actual relapses, PIRA may as much be a verdict about the way we currently follow peoples’ symptoms between their 15-20 min appointments every 6-12 months. That’s why we need to engage with apps, such as Floodlight or Icompanion, to name a couple, which have the potential to provide more granularity (daily/weekly measures). Several studies, including our SenseMS project we’re still hopeful to get off the ground, will explore how much we can rely on these apps. Transition between drugs is an issue. Without writing an entire blogpost, bottom line is once lymphocyte recovery has taken place, starting a new DMT is feasible & generally safe. An issue with cladribine is more pronounced lymphocyte depletion after starting when people switch from other drugs, such as DMF or Fingolimod. Again, generally speaking, this is not a significant adverse risk though case reports have raised questions about the timing of switch (when to stop one, and start the other).

      • Prof K – Any thoughts on the risks of switching to clad from Teri or Ocrevus?

        The most relevant factor appears to be total lymphocytes. However, what if total lymphocytes are good, yet CD-19 b-cells remain low.

        There is not a lot of research or data on this topic. I have been trying to find data on the rapid elimination of Teri, then immediate initiation of clad. As long as total lymphocytes are good.

        MD recently did a post relating to a failure of Fing to Clad. However trapping cells in the lymph glands compared to controlling the proliferation of lymphocytes seem to present different risk profiles when transitioning to clad.

        • So here is the dilemma….since CD-20 b-cells are already low, not washing out Teri could help keep b-cells in check during the reconstitution phase (possibly good). Current data indicates b-cells repopulate quicker than t-cell during treatment with clad, which could cause secondary autoimmunity problems. Conversely, not washing out Teri could result in an extended reconstitution timeframe, creating greater risk of infection/side effects.

          To wash out or not, that is the question nobody can seem to answer.

          • Thanks for the insight……heavy sarcasm added 😕

            Guess since I don’t have a medical degree, I am somehow qualified to make my own assessment without the insights of medical professionals.

            Figured with all the years of experience and research in the barts team, someone would have a few thoughts this situation.

          • You are asking a clinical question, so the only people who may answer are the clinical staff, they try not to give personal advice on the blog and are very busy with their day job and deliving with the extra duties around COVID-19 . Nurse ProfK for example.

            The T cells are not that depleted with cladribine and therefore when B cells return they are there and there is no autoimmunity problem.

            Teri is anti-proliferative

            I wonder when people switch down the therapeutic ladder

      • I keep a diary of all hiccups of my symptoms and read more significant events to my neuro at each appointment. He doesn’t seem to value much of these “data”. I wish there is a more standardized way for patients to record their journeys which can be taken more seriously.

      • “Transition between drugs is an issue. Without writing an entire blogpost, bottom line is once lymphocyte recovery has taken place, starting a new DMT is feasible & generally safe.”……………entire blogpost on this topic PLEASE.

          • Thank you MD! Any insight is better than nothing. Neither of my neurologist have experience with clad, so I am left to my own devices. Which is very unsettling, given my unique circumstances and DMT reaction history.

            However, I know the rules of engagement for the blog and I am sorry for crossing the line.

            I must say, not having Prof G, NDG, and Prof K available to help guide the MS blog family really sucks. Stupid COVID and anti-vaccine ignorance. I wish the military would just take over the vaccination process, we would be at 90% immunity in two months.

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