How does cladribine work?

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As promised, I now provide you with a link that will provide you with full and free access to the paper for fifty days. You can download, read and come back to ask questions. Here is the link.

https://authors.elsevier.com/a/1Yba37skoe-Ouc

Enjoy.

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11 comments

  • Thank you. As I’m still only part way through reading and non medical trying to understand it. Just wanted to note the my eosinophols dropped from 2.17 to 0.72, so it definitely had an effect on that. Don’t know if it’s significant but it did drop back to closer to normal range

  • Thanks MD.

    I do not understand why cladribine does not yield even better results for both progressive and RRMS than it does based on this publication?

    It crosses the BBB or is CNS penetrant which all the monoclonal antibody therapies do not. It states it destroys memory B-cells. Does this include the memory B-cells in follicles in the brain that are EBV driven? Does this go against the hypothesis of EBV controlled memory B-cells in follicles of the meninges of the brain propagating MS if cladribine does not work?

    • Its results on NEDA and relapse rate are as good or better than other DMT (Rotstein et al. 2015). Relapse rate is about 0.1 which is 1 relapse every 10 years. Alemtuzumab and ocrelizumab are no better than this. That is the point there is a common mechanism between the different DMT and so there will be common efficacy. It also suggests that ocrelizumab will work for longer than the 6 month dosing as occurs with cladribbine and alemtuzumab. Again conistent with known data.

      How do we know what it does in progressive MS the one trial lasted a year, which is not long enough. I could give you anecdotes but i won’t as they are rather meaningless to the big picture. Likewise I would say these DMT are not enough to control progression once sufficient damage is done, you need some thing extra. If you take the same demographic as used in the ocrelizumab trial I am sure it and other agents like alemtuzumab would work similarly. It is not rocket science it is simple biology

      Does it destroy B cells in the brain, we dont know because we haven’t looked. The amount that gets in the brain (25% of blood levels based on cancer use data) will depend on a number of factors including dose. Other factors are important, like how good are drug transporters at excluding it from the brain.

      As to Memory cells in follicles. I think we have to be clear what we mean, most so-called follicles are simply an aggregate of B cells. These are not classical follicles as found in lymph nodes. In lymph nodes, memory B cells and plasma cells are made in follicles but do not live there so looking for germinal centres (follicles) in CNS is not necessarily going to tell you where the plasma cells, memory cells are.

      • If this MOA theory is confirmed, and Clad is indeed introducing back the tolerance, does this mean that inflammation was switched off and that induced tolerance means that immune systems will keep everything in check? Getting rid of OCBs in the long term sure does point to that… So you could say that for those lucky few, MS is essentially switched off completely? What happens with other biomarkers in those (now OCB-ve) people? NfL levels, BVL? Do we know from your (at Barts) usage of Clad off-label or from that Polish study?

        I know that you can expect that result only if this was done early enough, and clad Off-label was usually offered quite late in the disease course… Is there even enough patients that received Clad very early and were they monitored to see what happened to them? What happened to the original people with Cis that were treated with Clad (Movectro?)? This is as early as it gets.

        • This has to tested and confirmed as there are altenative explanations. We clearly want there to be a reset of the immune response.
          We have yet to test the OCB, but DrK has NfL levels from a number of people I guess that will be presented at ECTRIMS 2019.

          • How do you know if immune response was reseted?
            no OCBs + normal NfLs + normal BVL?
            Is there a direct test for reintroduced immune tolerance?
            ECTRIMS2019? Ugh.. that’s in autumn! Is there a chance for a spoiler or two to be dropped here 😉 btw. AAN is much closer, or (hint hint) some journals have quite short review times 😉

  • This link has expired and can no longer be used to grant free access to the article. Could you please provide another link?

    • All our.papers are on the qmul website and when they become open access they are there. Check out the links provided. If not drop us an email and we will send it

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