The C-word

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Barts-MS rose-tinted-odometer: zero-★s (seeing red)

After my blog post on potentially curing MS, I have been criticised by several people in the MS community for using the C-word. Do you agree? Have I raised false hopes?

I am of the opinion that unless we define what an MS cure looks like and then look for it we will never find it; i.e. the holy grail will always elude us. Another factor is that if we are really curing some people with MS with IRTs (immune reconstitution therapies) shouldn’t the MS community know about it? Wouldn’t that shift the risk:benefit ratio in favour of the benefits? Just maybe more people will choose to be treated with AHSCT, alemtuzumab or cladribine if there was a small chance of a cure. One commentator has suggested I use the term long-term remission rather than cure. The problem with long-term remission is that it doesn’t quite have the same emotional impact as a cure.

One of my patients with both MS and breast cancer was bowled over by her breast cancer consultant who said to her, “we have an 80% chance of curing you of your breast cancer”. Saying “we have an 80% chance of putting your breast cancer into long-term remission”, just doesn’t quite cut the mustard.

If you have the time can you please respond to this three-question survey, which will take you literally 15 seconds to complete? Thank you.

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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.

59 comments

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    • Some commentators say talking about a potential cure raises false hopes and is unrealistic. I disagree.

      • If the consultant is of your opinion, and the patient responsive, and more time allotted for monitoring (i.e. more than 45min a year), I feel sure a lot would be achieved in the way of RECOVERY!

        • 45 minutes? You’re lucky. Barely get 5 in the last 3 years and even then it wasn’t with the consultant. Only for contacting the radiology department asking for a copy of my mri report I’d still be non the wiser 🤷‍♀️

  • Love the post i think cure is a good word, however its infuriating when you say “choose to be treated with IRT”. I would choose one of them in a heartbeat if i had the option first line but you dont. Only certain centers will use cladribine and the others are third line by which point their useless. Do more to change that and push neuros to be open about efficacy and real life patients( how they do on the drugs) and maybe more patients will be cured. You can call it whatever you like it wont make a difference untill we have better access to the drugs that matter.

  • I agree that defining ‘cure’ is key. For me, a cure is something that will put the toothpaste back in the tube.

  • When I started on cladribine, after having read a lot about it on this blog and elsewhere, I asked my consultant the question: if this drug works as you (the IRT proponents, generally and collectively) hope it will, then isn’t it essentially a cure? My consultant hesitated slightly in replying, but as she knows that I am not one to panic about my MS nor to cling to false hope, the gist of her response was yes – though I can’t remember whether she referred to long-term remission or used a similar term instead.
    Although I’m not opposed to the use of the c-word in this instance, a potential sticking point in my view could be that ‘cure’ may, to some, suggest reversal of prior damage, or lessening of existing symptoms.
    I’ve yet to see if cladribine (2 years now complete) will cure my MS, but am under no illusion that my existing symptoms (thankfully relatively mild) aren’t here to stay.

  • I think the word is appropriate if the disease is stopped in its tracks, never to return. But, I think some people expect a cure to include restoration.

  • Talking about a cure is appropriate-setting a goal is the first step to achieving it! Sometimes serindipity strikes & we reach a goal without striving for it-but that is no way ti fight this enemy

  • In my view, the hope / potential for a cure is an effective DMT in its own right. When diagnosed with CIS, i convinced myself the first episode was genuinely an isolated incident. A phenomenon. Once my symptoms subsided, i never even thought about it again. In hindsight and now that i am more knowledgeable, this was naïve but i had 4 good and relaxed years until episode number 2. Since then (18 months ago) i probably think about MS every waking minute of the day. I am sure this hasn’t helped my disease course. It is one of the reasons i considered going abroad for HSCT and i am now pursuing alemtuzumab, to have the feeling of being potentially cured, of shutting the lid on MS and releasing the mental burden. I am realistic. I know that i will never forget about it now but the hope of being cured, will, i feel, have a positive mental impact for a number of patients. Take this away and the mental burden of the disease is greater in my view and this can manifest physically. Survey completed. Team cure.

  • I rather have false hope than no hope at all. Terry wahls has also been criticised of giving people false hope. I am not one of her warriors and the diet did not work for me. But when I am down I find strength in pwms who are doing well. Also the effort from people who are working on finding ways to give pwms a better future helps a lot. Fighting and trying to be positive are the only 2 things I have battling ppms. A pessimistic view from people in the MS community will not help with this

    • I too am not a Wahls warrior- but I’ve never found out how to get NMES, which is a crucial part of the protocol. Where did you get it?

      • Ditto Peter Davey. Heard a lot about neuromuscular electrical stimulation (NMES) for muscle strengthening and retraining, maintenance of muscle mass and strength during prolonged immobilisation. Have never found out where you can get it in UK. Seems widely available in US.

  • I think you are correct to talk about a cure, but making sure the patient grasps the full severity of just what MS is and the lifechanging impacts it can have. I started my MS journey at 30, (I’m 52 now) and the initial prognosis that I received was ‘sketchy.’ I don’t hold this against the Neuro, I just think that back in 2000 our scientifc understanding of MS was equally sketchy.

    Winding forward to 2018 I was given alemtuzumab and was, what I would call, ‘properly counselled’ at that tiem – as I had been since about 2014. I just wish that alemtuzumab had been around for MS back in 2000; if it was and I had been given it, I would be considering my MS cured. Now, I believe that I’m in remission hoping my exisiting diabilities have flatlined – that’s what the MRI’s are suggesting. I’m currently 8.0 on the EDSS scale.

    I only make the distinction between cure and remission for me because my CNS had been whacked pretty severely between 2000 and 2018. But I accept that you can only take the DMT’s that are licenced at a particular point in time.

    I just find it tragic that as we stand currently, (I still believe this to be the case in the UK – apologies if not), alemtuzumab isn’t available as a 1st line treatment. It’s around so it should be offered, (IMHO and after proper counselling of the patient on the possible side effects). Again IMHO, hitting MS aggressively with Alemtuzumab on 1st presentation of MS symptoms would give as best an outcome of an MS cure, as possible.

  • Is there really anyone with MS that has been cured? I hadn’t been aware of it. About your patient who had breast cancer we would need to know her age, what type of cancer histology she had, what her treatment had been, how long she had NEDA. Depending on some of the answers to that she may indeed be cured, otherwise her Oncologist is chancing his/her arm.
    The choice of language is not only between Cure or Remission.
    Let’s learn from Oncology where some patients had been told that they were Cancer Free, only for the disease to raise its ugly head anytime thereafter and patient and families to be super-angry. Using and explaining NEDA is an acceptable alternative imo. Not so sure about MS though, unless the person is completely asymptomatic how can you even say NEDA? Neurology investigations are not sensitive or adequate yet, well that’s my understand.
    In summary I would say Noooooo to using the cure word in 2021 It may lead to more psychological fallout than you can begin to imagine.

  • Completely with you on this one Prof G. A cure to stop any further damage is my definition of an MS cure. PwMS are not incapable of digesting the facts and seeing the varied results – i know there’s no magic bullet, but if I got to 5yrs post hsct with NEDA I’d be celebrating that and letting myself move forward thinking I am cured.
    Whether or not I one day relapsed may change that fact but there’s lots of reasons to move forward as a person free from MS and enjoy life. (And it’s happening for people right now! )

  • Oh boy! So now we have to define “cure”. I think that’s a big word to use with MS. As a person with MS it means to me that it would go away, that I wouldn’t have to deal with it anymore, that it wouldn’t get any worse even if I still had the the damage done.
    But I also think that “cure” means hope which is sorely missing in the world of MS. I like the word.

    • Re: “So now we have to define ‘cure'”

      We put a working definition in place 8 years ago. The problem is the MS community don’t accept it 🙁

      • Please advise what the definition is? Would love to know. My wife’s been diagnosed with MS 6 years ago, been on Copaxone (Glatiramer Acetate) ever since, had no relapses and her MRI shows no deterioration and even some damage healing. Isn’t that almost ‘cured’. Mentally, she doesn’t want to receive any MS correspondence or magazines, as she feels worse if she’s reminded of it all the time and the potential deterioration. I think ‘cure’ will mentally bring hope that something can be done.

        • “My wife’s been diagnosed with MS 6 years ago, been on Copaxone (Glatiramer Acetate) ever since, had no relapses and her MRI shows no deterioration and even some damage healing. Isn’t that almost ‘cured’.”

          No..haven’t you been been reading the blog…she does well now but in 5… 10 or 20 years she could need a wheelchair..hsct or alemtuz is what she needs….not Copaxone

  • I think defining a cure is the tricky bit.

    MSers at different stages of the disease will have different views of what a cure means. All MSers would be thrilled with a treatment / mix of treatments which would stop MS in its tracks ie no further worsening. But is that a cure? Many would include an element of improvement in a definition of a cure. For wheelchair users it might include walking again (perhaps with a cane). For someone with CIS it might mean never going on to develop full blown MS. Not so long ago an RRMSer may have described a cure as no more relapses, but MS proved way more complicated and addressing smouldering MS / the real MS is more likely to provide a cure (if a cure is defined as stopping MS in its tracks).

    For MSologists a definition of a cure might include no new lesions, no sign of inflammation on MRI scans, normalised levels of brain volume loss and nfl. Perhaps no sign of ebv in the CNS.

    Currently HSCT and Alemtuzumab may provide a cure for some MSers, but the drugs used are pretty agricultural. Going forward a cure is likely to come from a mix of more targeted therapies which address: the cause (?virus); smouldering MS; the external immune system response; and promote some repair (?remyelination). Until then, it looks like HSCT and Alemtuzumab are the only players in town.

  • Completely agree with you, that we need to define a cure, in order to have a fighting chance of reaching one. Also in this age of outcome measurements, we need to define the outcomes. If I had a magic wand I would want HSCT, cladibrine and alemtuzumab to be available as a first line treatment on the day of MS diagnosis. Surely as a one off cost, HSCT has to be a more cost- effective way, than decades of seeing Consultant Neurologists, MS Nurses, MRI nurses, infusion clinicians, lumbar puncture clinicians, neurophysiotherapists, physiotherapists, physiotherapists and OT’S?
    Obviously I am a layman but I also believe that the NHS needs to learn from the reputable clinics abroad how to decrease mortality and infection rates post- AHSCT.

  • Until we understand the real pathology of MS where is even the ground of talking about a cure? One can only take 1 side, either warning everyone even the strongest treatment out there may not be enough and people should take the strongest because benefits always outweigh risks or take the appropriate risk and be happy about it.

    This is not false hope, this is misleading pwMS taking on more risks for false expectation. Oh I would love to hear the C-word, but not how prof G describes it.

  • My neurologist told me that he was aiming for me being free from relapses for at least 5 years when I started Lemtrada as a first line dmt. He didn’t use the word cure but said in cancer terms that would be remission so his aim was to put me in remission. I think employment protection is still needed because of damage already accrued so long term remission is more likely to support that – as being cured, to me, would suggest returning to normaility – the me pre diagnosis.

  • I do not know the exact medical definition of cure. I think the consultant needs to know the patient and their expectations
    If the patient is happy that their MS is definitely not going to get worse then it is a cure. If the patient expects to regain the functions they lost that led to their diagnosis and subsequent MS problems then it is not a cure but permanent remission.

    Chose your words with care and be honest

  • I really liked that post. How do you want to achieve a goal if you can’t name it? First step to go somewhere is to know where where is. Then you start going.
    Beside that, cure to me means no disability progression perceived by the patient, no new lesions, no relapses, no OCB, normal sNFL/cNFL, normal immune system parameters such as cytokine profile and CD4/CD8 ratio. That is look like a healthy person from biological point of view.
    For me MS is the process that damages nerves and leads to disability and the cure is what stops this process to occur.
    Damage repair is something to do on top of a cure. As reported several times if you don’t stop the damage first you will not be able to repair.

  • But is there a cure for arrogant neurologists? “There is no treatment for ppms and your time is up” I will not name and shame this person)

  • Nothing wrong with getting peoples hopes up as long as someone is actively researching these different ideas and proving/disproving them
    .
    Trying to cure MS is more interesting that trying to manage MS. My only issue is the EBV followers. While we do hear about potential cures and causes every week, like that pistachio remyelinates brain cells or was it a cashews post. Should EBV != MS, I think a lot of people are going to have a nuclear meltdown.

    • We have a lot of good evidence to suggest EBV is the cause of multiple sclerosis Professor Gavin has made a few posts about it.

  • Its fine to use the word cure several ms charities use it in their website to describe their objective.

  • Pretty sure I recall a prior post where you proposed talking about remission and not cure. The premise being that cancer is more particularly in remission and not cured as the general public perceive the word and as with cancer monitoring is required, with the acknowledged risk of the cancer reappearing. Think I remember you suggesting that long term remission is what is achievable with the higher efficacy treatments and that it is a fair and balanced way to view what treatment can achieve and that a layperson idea of a cure may never be achievable with MS.

    I’m interested you have a 180 view of this now, because I was persuaded that aiming to achieving remission is a valid stance and may well be more realistic an aim than cure when dealing with the immune system – however much I’d like to see the full blown cure for every PwMS! For myself as someone who’s received Alem I find it easier to think of being in remission than cured, because this way there’s not the risk of my forgetting the MS can reignite at anytime.

  • 2014

    Concluding remarks
    In this chapter, I have discussed different aspects of the concepts of health,
    illness, disease and cure. The word “cure” is very powerful, evoking images
    from folklore and religion. Nevertheless, it is possible to arrive at a rather
    precise definition of this word. For the purposes of this thesis, I shall adopt
    the view of clinician and scientist and define cure of MS as freedom from
    clinical and biological disease activity (definition 2 & 3) with this proviso:
    the cure only applies to the RRMS part of the disease. In the next chapter, I
    will discuss hematopoietic stem cell transplantation, which could be a cure
    for RRMS

    Curing Multiple Sclerosis

    https://uu.diva-portal.org/smash/get/diva2:714003/FULLTEXT01.pdf

    Already in 2014 this people have go against the tide

    They were the pioneers there work was not acepted

    No wonder you are getting hit form all sides

    There is no intere$t in $ cur$

    Nice post

    • He seems to have read our 2013 definition in MSARDs. I formulated the definition around the alemtuzumab responders.

      • Reversal of accumulated disability.
        Lastly, cure could encompass reversal of accumulated disability. A true
        reversal would require restoration of damaged tissue to a normal
        cytoarchitecture and in most cases neurogenesis. With few exceptions this is not possible in mammals, and certainly not in any disease of the human
        central nervous system.97 For patients with a large amount of accumulated disability this aspect of cure will be very important, typically patients with long-standing disease or progressive forms of MS.

    • Banwell et al. Editors’ welcome and a working definition for a multiple sclerosis cure. Multiple Sclerosis and Related Disorders. 2013; 2(2):65-67.

      …. Defining a cure in MS is a difficult task. How long should we wait before declaring a victory; 15, 20 or 25 years? Oncologists have back-tracked on this issue and instead of a cure they now prefer to use the term NEDD, or no evidence of detectable disease, at a specific time-point knowing full well that a limited number of subjects will relapse and present with recurrent disease after this point. We propose using the term NEDA, or no evident disease-activity, at 15 years as a starting point for defining a cure. Why 15 years? This is the most commonly accepted time-point used for defining benign MS and therefore it is a usual endpoint. In addition, the median time to the onset of secondary progressive MS is ~10-11 years (Kremenchutzky, Rice et al. 2006) and is well within the 15-year time window of our proposed definition of a cure. At present NEDA is defined using a composite of a) no relapses, or b) no EDSS progression, or c) no MRI activity (new or enlarging T2 lesions or no Gd-enhancing lesions) (Havrdova, Galetta et al. 2009; Giovannoni, Cook et al. 2011). This description is currently based on data that is routinely collected in contemporary clinical trials (Havrdova, Galetta et al. 2009; Giovannoni, Cook et al. 2011). The definition of NEDA will evolve with technological innovations and clinical practice, and in the future, it will almost certainly include MSer-related outcomes, grey matter disease activity, an index of brain atrophy and hopefully a CSF biomarker profile…..

      • “i know there’s no magic bullet, but if I got to 5yrs post hsct with NEDA ”

        I know one of Dr. Burt’s patients who relapsed after 6 years and had to go to
        Mexico for another hsct.
        Another one of Dr. Burt’s patients relapsed after 11 years.

        I am sure the same happens with Alemtuz/Lemtrada..but the failures are
        probably right up front in the beginning.
        Or Maybe not…I don’t know.

        • I relapsed 5.5 years post HSCT (Cyclo+ATG), there are people on HSCT groups who relapsed after 7+ years. On Lemtrada group there are people who relapsed after 10+ years, one guy recently (in May) relapsed after 12 years after second Lemtrada dose. I think none of these treatments cures us, it just kicks the MS into remission, though the underlying cause of the MS is still present, if the thoery about EBV is valid – doing lemtrada/HSCT makes “not much sense” if after these treatments people are not being given some antivirals for EBV, to let the immune system and limphocytes to “rebuild” in the environment free of EBV contamination. But that is just my theory on that, and I am probbably wrong…

          • I didn’t see your comment here too Lukasz , was replying to comment above in my last one. Im sorry hsct didn’t last for you . I have often thought a similar thing to you when researching hsct.. is it really just a long acting dmt if we see the durability drop so much in yr3,4,then 5?
            We will find out more in time I guess

        • Yes, and many don’t relapse at all too. The nature of talking about defining a cure is quite individual and (I think) about patients choosing a point at which they feel the mental freedom from being a PwMS after a period of remission , and as I said in my original comment ‘whether or not I relapse one day’ beyond that time, life is too short to not move forward and celebrate. That’s something well learned from cancer patients in remission too, celebrate the milestones and enjoy what’s good while it’s good 😊

      • Not wait 15/20/25 years, wait till age 85 or 90
        That’s my time horizon, now that I’m in my late 50s and my parents are in their 80s

  • I have been treated with cladribine and there has, thankfully, been no change to MRI. Stable disease, feel great 😊

  • I just want to say thank you Professor Gavin for everything you do for ms research. I really appreciate the fact that you are moving forward the testing of anti-ebv research into trials. I love the fact that I can be up to date with everything in regards to ebv thanks to you and your team.

  • I answered yes to all three questions.

    When most laymen hear the word cure, they think of two things. 1) stopping the disease and the disease never returning and 2) restoration of what was lost or at least significant improvement. in functioning.

    So unless you mean all of the above, “long term remission” is IMHO the best term.

    Long term remission is best if you can’t restore function and/or you can’t reasonably guarantee the disease won’t return.

    But since you are interested in neuro-restoration as well, you should talk about a “cure” judiciously. Ideally you want to “cure” (stopping AND repairing the disease process) MS if possible.

  • Oh I so wish I knew whatI do now 15 years ago when first diagnosed. Would have travelled abroad for HSCT or at the very least found someone to prescribe Campath off-label. Crystal ball is such an amazing medical instrument! Would also have started on a sodium channel blocker from day 1.

  • At what time after a supression of type B limphocytes (ocrelizumab, alemtuzumab, HSCT) should the “EBV antiviral” (let’s say tenofovir alafenamide) drug be given for it to achieve the suspected efficiacy of resetting the immune system and allowing B lymphocytes to rebuild in an environment free of EBV replication? Should it be given before the treatment, right after the treatment? How long is it supposed to be given? As long as the treatment lasts + time needed for B cells to fully rebuild to it’s normal levels, or forever? I know that this are just speculations, but what are the medical theories behind it? (not the clinical trial results etc.)

    Cheers!

    • Well in theory you would need to use tenofovir alafenamide ( if and when it gets approved ) as soon as you are diagnosed in order to to drop the ebv viral load as soon as possible. The question remains as to how much tenofovir alafenamide gets within the central nervous system. I suspect we might need tenofovir alafenamide with another antiretroviral capable of crossing the blood brain barrier adequately to get rid of everything but I am speculating perhaps Professor Gavin would be better suited to answer. Anyhow we are moving in the right direction.

      • Thank you for responding,

        Is it me or is tenofovir alafenamide already an approved drug used to treat hepatitis type B and it is pretty safe in terms of side effects.

        Does it really need to cross the BBB if the anti-CD20 or alemtuzumab/anti CD-52 are blood brain barrier penetrants?

        I asked abut the “when and how long does it need to be taken”, to find out if it makes any sense to start taking the antivirals for example 3 years after an induction treatment, lemtrada/HSCT? When the immune system had already fully rebuilt in the EBV environment.

        Cheers!

        • “if the anti-CD20 or alemtuzumab/anti CD-52 are blood brain barrier penetrants?”

          All the -mab drugs are large molecule and can’t pass BBB..
          Rituximab..Alemtuzumab..etc…

          • Thank you,

            Yeah, I realized it a few hours ago. That bothers me right now – why is Alemtuzumam considered a “cure” for some, if it can’t pass BBB?

        • “why is Alemtuzumam considered a “cure” for some, if it can’t pass BBB?”

          It only works in rr..massive peripheral depletion is enough to reset the immune system. The real question is how many fail treatment over 10 years…we know in hsct it’s 30% at 4 years
          and 40% at year 5 in active rr. Don’t think anyone has numbers
          for alemtuz..but it will be worse than hsct.

          “The transplant saved my life–I was, and still am, beyond fortunate. For four years it helped me feel almost normal again. And I purposefully took every advantage, living life with my right foot firmly on the accelerator, figuratively and literally. It allowed me to drive again, travel the world again, and even snowboard again. But I knew that I might have to write this post one day.”

          “As evidenced by the just released 3-year update of HALT-MS in JAMA Neurology, the success rate of the trial has been unprecedented in MS, with nearly 80% of patients showing no evidence of disease activity after three years, and with some patients seeing a marked reversal in disability, myself included (2.5 EDSS points!). Unfortunately, it appears that with time the treatment’s durability is tested, as early numbers suggest fewer than 70% exhibit zero disease activity (relapse, new lesions or EDSS increase) at year four, a figure that drops below 60% at year five. Still powerful results, but far from across-the-board remission.”

          https://forums.activemsers.org/forum/activemsers-org-forums/dave-s-sct-journey/1826-gains-from-my-transplant-are-slipping-begrudgingly-weighing-plan-f

          • Thank you for replying,

            There is 10-12 year data on Alemtuzumab, which shows that after 12 years 34% people remain NEDA, and about ~20-25% progressed with disability within that time, which to me seems like a large success. The question is what happens after that. Another question is – if people relapse and have have new T1/T2 lesions however they do not progress with disability and have a “regular” brain atrophy – isn’t it the best DMT that pwMS can get? A relapse once a few years or a new T2 lesions once a few years without impact on disability is perhaps the best we can get right now…

            I am leaning toward Lemtrada myself – however I wonder if going on Lemtrada + TAF (antyviral) is reasonable or rather stupid without any results from ongoing clinical trial (the one that started in London on 15 of May 2021). I guess it will be very hard to persuade a neurologist to jump on it without any clear evidence that it helps.

  • For what it’s worth I will give my ‘uneducated’ opinion. When every person with ms, regardless of age, is treated into permanent remission, call it a cure. Until then it’s word games.

  • When the root of MS is found (EBV?), the pathology genuinely understood and a real treatment (antiviral) is proven, then cure is an appropriate term.

  • How do you feel the question of cure vs term long-term remission fits with the debate about benign vs currently inactive RRMS – ie a description of what is happening now vs how things may turn out over a longer period of time?

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