Tickled pink

T

Barts-MS rose-tinted-odometer: ★★★ (seeing pink; tickled pink)

Thank you for completing yesterday’s poll. It is quite clear that you, our blog readers, want us to prioritise the following changes to the way we prescribe DMTs in the NHS. The most important priority is for pwMS to access immune reconstitution therapies (alemtuzumab, cladribine and HSCT) early as 1st-line therapies for active MS. Please note if you have rapidly evolving severe MS (RES) you can be treated with alemtuzumab and cladribine first-line, but outside of this very small group of patients, we can’t prescribe IRTs first-line. For more information on RES vs. active MS classification system and its implications for some pwMS, I would recommend you read ‘Watchful Waiting 2‘.

The next priority is access to natalizumab, a very high efficacy therapy, as 1st-line therapy for active MS. At the moment the only agent that covers this broad bracket is ocrelizumab. My reading into this is that if you don’t have RES but just active MS, you would like more choice and not simply have one high-efficacy option first-line. 

The third priority relates to treating advanced or progressive MS, i.e. getting rid of the stopping criteria when people with MS reach EDSS 7.0 (wheelchair) and liberalise the prescribing of ocrelizumab and siponimod for primary progressive and secondary progressive MS, respectively. My interpretation of the latter is that you want to challenge the active vs. inactive progressive MS dichotomy

Finally, treating asymptomatic MS and liberalising the use of platform therapies and fingolimod is not a priority. This worries me because as we move into an area of testing and exploring the induction-maintenance paradigm we need to be able to use platform therapies 2nd- and 3rd-line. I have made the point before that pwMS are not going to be able to remain on anti-CD20 therapies indefinitely because of the potential risks; for example, as your immunoglobulin levels drop and serious infections increase the benefit-risk balance changes. Therefore, we are going to need to test de-escalation approaches to derisk anti-CD20 and other chronic immunosuppressive treatments. This is the rationale of the iTeri study that I have proposed doing; i.e. induction with ocrelizumab or rituximab followed by maintenance with teriflunomide. 

I would be interested to know if you are surprised by the poll’s findings? 

I wonder if the Australian neurologists chuckle when they read this sort of blog post? They have no restrictions on how they treat MS and can use any DMT, including AHSCT, as they and their patients see fit. If only the NHS would allow us to practice in this way 🙁

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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

41 comments

  • You keep saying alumtuzumab can be used for res ms first line but this isnt the case! I was catagorised as resms and could only be offered cladribine or tysabri due to some safety guidline and this was in december last year. If the guidline has changed could you please post the guidline change information in the comments ?

    • Having been in this for a long time, only a fool would come up with a number as it’s sure to be wrong.

    • Re: “How close are we to a cure (5-7 years ) ? Maybe a bit less or more ?”

      Less. I personally think a minority of pwMS treated with IRTs are cured already. They tend to be young pwMS treated very early. The purpose of the C-word post was to raise the issue and say if we don’t define and look for it we won’t find it. And the purpose of the poll was to see if the MS community wants the option of MS being treated with an IRT.

      https://multiple-sclerosis-research.org/2021/05/the-c-word/

      • Prof G,

        HSCT and Alemtuzumab have been around for a while – early work on testing Alemtuzumab on MS patients started in the early 1990s and the Canadian BMT trial started in the early 2000s.

        Are there any promising new therapies in trial which might offer the possibility of a cure for MS (for some)? If such a therapy (less traumatic than HSCT) was a available in 2-3 years time, it might make a patient think carefully about whether to get HSCT this year or next year.

        Would a therapy which addressed the real MS / smouldering MS potentially offer a chance of a cure (if a cure was defined as stopping MS in its tracks)?

        Have a good weekend.

        • There is a race fot BTK inhibitors going on right now, it is believed that they might work for smouldering MS and as a maintenance therapy.

          • I guess I ask why was the BKT data not as good on paper as with other DMT

      • “I personally think a minority of pwMS treated with IRTs are cured already.”

        No doubt….but the reason hsct/alemtuz don’t work for the majority is that they
        don’t alter genetic deficiencies that lead to uncontrolled EBV…and they
        don’t remove EBV by themselves…all they do is deplete b-cells..t-cells

        Immune repopulation analysis of HALT ms myelo trial:

        “In general, the repopulation of immune cell subsets progressed similarly to 2 years for all patients studied, regardless of clinical outcome.”

        “Although none of the observed treatment effects correlated with clinical success, patients who remained healthy throughout the 5‐year study had Significantly higher absolute numbers of memory CD4 and CD8 T cells in the periphery prior to HSCT treatment.”

        https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543487/

      • Re: “Less.”

        Okay that sounds good if that’s less than 5-7 years.

        I agree defining what a cure looks like is important to have.

      • “ I personally think a minority of pwMS treated with IRTs are cured already”:

        Would you include cladribine in this category as well? Have you or Prof. Schmierer seen any patients stabilise on it above the 4-5 year mark post cladr. initiation?

        Thank you beforehand for your reply.

          • May I ask whether this person is still stable? I am about to start Cladribine and having this as a potential scenario to hope for would give me further courage.

            Thanks again

          • I don’t know profK treated may people some with progressive as well as relapsing MS, an abstract has just been submited on redosing of our cohort

          • Cladribine is in a risk sharing scheme whereby any break throughs and switching after the first two cycles up to year 4 and the company re-imburses the Government for the two cycles….They should just give another cycle for free, why because with alemtuzuab 2 cycles is enough for 50% of people 3 cycles and it is 75-80% of people. However, I understand the payback has been very low, well below the 50% failure rate with alemtuzumab, which good news
            COI: Multiple

  • They don’t surprise me as quite reflective of how I responded, athough hsct wouldn’t be for me!!! I suspect my responses are biased by 7 years of blog reading. Would be interesting to see the same survey completed by uk neuros.

    • Yes, this poll is biased by the readership who are well informed about the issues raised with this post.

    • Would be interesting to see the same survey completed by uk neuros.

      Ha Ha you really do want the Blog to get closed down….Maybe if we saw what was offered and used it may give us a clue what people think.

  • I am not surprised by these poll findings. Regarding the outcome – ‘treating asymptomatic MS and liberalising the use of platform therapies and fingolimod is not a priority’, I would imagine this finding is likely more representative of the people reading this blog, and these people not being represented, ignorance is bliss

  • It does feel as if you’re a voice in the wilderness and that the reality here in the UK is so far removed from the Australian stance you (AND WE!!) would like to see adopted.
    If there were a comprehensive national survey of every PwMS then I’ve no doubt of the following: most will have been given a limited diagnosis = RRMS or PPMS, with no mention of ‘active’ or RES etc. Secondly that most will not be given an option of DMT, simply told what meds they will be put on. Thirdly, the minority for whom this is not the case are either well informed and assertive PwMS or fortunate to have the rare benefit of a switched on, proactive neuro.

  • “They (Australian Neuros) have no restrictions on how they treat MS and can use any DMT, including AHSCT, as they and their patients see fit. ”

    This is totally wrong..Aussies all go to Russia…once again false hsct info goes into the world.

    Won’t even go into fact you think hsct in u.s. needs trials to be licensed by the FDA..the chemo
    was licensed in 1959 so anyone can do hsct in u.s.a now but no-one does it. Why..?..Neuros want
    cushy jobs and pharma wants everyone on $100,000 yearly Ocrevus for life.

    https://www.youtube.com/watch?v=MwUgzuNQZWw

    https://multiple-sclerosis-research.org/2018/01/is-hsct-for-everyone-or-not/
    “The HSCT zealots would want you to believe that HSCT is the solution to MS and that we the neurologists are preventing you from accessing this curative treatment. Are they correct? Or do we need evidence from randomised trials?”

    https://multiple-sclerosis-research.org/2020/01/premature-ageing/
    “We do post your comments, but we are about to stop posting your comments on the grounds that you promote/advertise HSCT and that you are a troll.”

    No..I don’t believe hsct is a cure it has solid 30%-40% failure rate at 3-7 years…and Alemtuzumab does
    anybody even know..? got to be slightly worse than that..as on FB groups some relapse +10 years…

    • I am aware that several Australian centres offer AHSCT. Not sure where you get your information from. I suspect they don’t necessarily offer it 1st-line, which seems to be what happens across the world including the UK.

      Please don’t shoot the messenger 😉

      • “Not sure where you get your information from.”

        from 60 minutes Australia..
        one woman had her hsct stopped mid-procedure

        • You need to remember that 60 mins tends to pick up the extreme stories and can now be quite biased in. their reporting of “facts” in order to increase ratings. AHSCT in Australia may not be first line from many neuros that is their choice (as much as we may think it is the wrong choice) it is not being dictated to them by “guidelines”, it is their clinical decision. Alemtuzumab and cladribine are certainly regularly used as first line in Australia.

          • “Alemtuzumab and cladribine are certainly regularly used as first line in Australia.”

            In the u.s. they aren’t…and nobody does hsct
            except in a few trials.

    • In my country (the Netherlands) 1 shot of Ocrelizumab (300mg/ml) only costs €5856,85. So if you are on a 26wk cycle you only need 2 shots a year.

      In my case with my neuro who customizes my meds, I just get about 3 doses per 2 years. No where near your $100.000 each year!

      • “1 shot of Ocrelizumab (300mg/ml) only costs €5856,85.”

        That’s about the $6,000 monthly u.s. cost of Copaxone u.s.
        Ocrevus costs about $66,000 u.s. but you have to add infusion fees

        “Total bill: $123,019 for two Ocrevus infusions taken as an outpatient.”

        So I underpriced when I posted $100,000 for Ocrevus
        Well over cost of 2 hsct procedures overseas..pharma absolutely
        loots u.s. economy..w/her symptoms she needs hsct before she becomes
        progressive..hsct drugs are already FDA approved so any Dr. can do it here
        but none do.

        My sister had BMT which is more involved than hsct as you have a bone marrow donor but it cost $500,000….so $50,000 for overseas hsct is a bargain

        https://www.npr.org/sections/health-shots/2018/11/27/668663222/chronically-ill-traumatically-billed-123-019-for-2-multiple-sclerosis-treatments

      • “No where near your $100.000 each year!”

        Correction it’s $142,000 a year…
        “Sticker shock doesn’t even describe what I felt as I looked at the amount: $142,546.40. That is my entire bill for this twice-yearly treatment. It’s not just the cost of the drug, but also the use of the clinic services and all of their equipment and personnel. But still, that is a whole lot of money.”https://multiplesclerosisnewstoday.com/2018/07/12/ms-ocrevus-sticker-shock/

          • Yes, the cares act has issues with interpretation. Insurers can require their insured to go in network for Covid type care. I must go to in network facility and meet medically necessary standard or my insurer refuses to pay. It’s led to mixed messages about testing: my insurer saying it will only pay if I go to specific in network provider and it’s deemed medically needed, and my local municipality offering “free” testing covered by cares, but insurer saying no way. Instead of risking an unexpected bill of $1200 to test whole family at thanksgiving time, I tested myself, the only person who met medically necessary requirement because of dmt.

        • Yes greater than $140k. The infusion center is separate cost. I have so called Cadillac plan through hubby employer, but my co-pay is over $2k. Twice a year, I spend about 3 hours or more verifying my insurer will cover cost. My last infusion was postponed because insurer didn’t have all paperwork to approve, meaning I would be responsible for cost until insurer approved. I had reason to fear. A paperwork snafu at hospital 6 months before led to me getting billed $140k directly. It took several nail biting months to straighten out. Obviously, US doesn’t have universal health coverage, so the free market mostly governs cost, as well as R&D investment costs and greed.

      • Except normal dose is 600mg twice per year. It only comes in 300mg vials to allow for the split initial dose.

        Add in the infusion and a bunch of monitoring and you are somewhere between 25-30K per year – if nothing else goes sideways. I presume that applies in most of Europe (I know it’s in that vicinity in Switzerland too).

  • Australian neurologist here, using also DMTs apart from AHSCT regularly, despite being in relatively isolated rural practice. Accessing, swapping, optimising for patients’ needs rather than bureaucratic or incentivised reasons is fantastic. Remain concerned about long term use of CD2O therapies and how to de-escalate but enjoy the therapeutic freedom.

    • Always nice to see neurologists accessing and responding the Blog posts and as a UK citizen with MS I sincerely wish that there were dozens of neurologists here who did the same!

  • Not sure the platform therapies are gonna be an issue for much longer – leflunomide (which is just the prodrug of teriflunomide after all) is dirt cheap to begin with and teri and DMF will go off patent at some point in the reasonable future, too. AFAIK, Mylan is in courts with Biogen over DMF.

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