Friday, 15 August 2014

ClinicSpeak: natalizumab or alemtuzumab?

Wow, MS DMT counselling just got very complicated. Natalizumab vs. Alemtuzumab #ClinicSpeak #MSBlog #MSResearch

"In clinic on Tuesday I saw two  patients with rapidly-evolving severe MS who were eligible for natalizumab under the current NHS England's guidelines. One patient was a young man naive to first-line treatment with a poor prognostic profile (high lesion load on MRI, including posterior fossa lesions, and early disability in motor and cerebellar systems). The second patient is a young woman failing fingolinod (two disabling relapses in the last 6 months) having previously failed interferon-beta. Up until now the discussion for both of these patients would have been simple and I would have offered them natalizumab. I have a well-oiled summary of the risks and benefits of natalizumab and how we manage and de-risk the PML problem if they happen to be JCV-seropositive. But things have changed, we now have alemtuzumab as a therapeutic option for these patients. When I started discussing alemtuzumab next to natalizumab with these two patients things got very complicated."

"How do you compare a maintenance and an induction strategy with each other? When I mentioned the rates of long-term remission on alemtuzumab, and the potential an induction therapy offers regarding a cure, things got messy. I now realise that I can't mention the C-word without defining it. When I tried to define the C-word and discussed the potential of a cure, both patients were lost. Despite this it was clear that a potential cure is the alemtuzumab trump card. The promise of long-term remission, and a potential cure, is what outweighs the risks of being treated with alemtuzumab."

"The MS nurse who did the clinic with me, and I, have now decided to work on a better way of comparing the merits of these two drugs; we need to avoid mentioning the C-word. However, without the C-word, natalizumab, particularity if you are JCV-seronegative, would win hands down based on a risk-benefit analysis. The exception being for patients who are planning to have children, particularity if they want to fall pregnant in the next few years. An induction therapy is very appealing for young woman wanting to have children."

"At the end of the clinic I realised that if I am going to compare natalizumab with alemtuzumab I will need at least 60 minutes to go through the pros and cons of each therapy and their relative merits. Then each patient will also need a follow-up session to ask further questions. Counselling regarding DMTs just go a whole lot harder and more complicated. The following table tries to capture the issues that will need to be discussed when comparing these two agents. This is why true patient-decision making may also be an unrealistic expectation."



"Do you have any questions or comments? Please note this table is my first attempt at a very difficult task and will need some thought, in fact some very deep thought."

CoI: multiple

23 comments:

  1. Great blog, with clear advantages and disadvantages of both drugs, but then...

    and then, out of the blue "This is why true patient-decision making may also be an unrealistic expectation."

    I'd say "this is just why patients need to be leading in the decision making"

    Maybe you could elaborate a bit more on the 'this is just why'' that you stated, because it is all but clear to me.

    Thx!

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    1. Re: "This is why true patient-decision making may also be an unrealistic expectation."

      What I meant is that it will be hard for MSers to make an independent decision between these drugs; simply because the background information and knowledge required to inform an independent decision is very complicated. In my opinion it is going to have to be a shared decision.

      Delete
  2. I rather doubt it if this would make the choice easier for an average patient. :-)
    After reading this I would like to know more about autoimmunity risk of alemtuzumab. Thyroid problems can be managed, what about other risks? ( but your table almost makes the case for alemtuzumab, at least for the JC positive patient with very active disease!)
    But then again there is the FDA problem...

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    Replies
    1. Re: "After reading this I would like to know more about autoimmunity risk of alemtuzumab."

      I agree. There are a lot of posts on this topic on this blog. What I will do is assimilate all the information into one post that will allow you to make an easier decision.

      Delete
  3. Finally a head-to-head post!

    I have been compiling a comparative spreadsheet for more than a year now, with anecdotal evidence at best!

    I suggest we add a permalink to the menu of this blog, start with your table and keep adding to it over time.

    The most obvious moving variables are the C-word and risk stratification - this little project can evolve into personalised sections for different patient groups (teenagers, wannabe mothers, busy men....)

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    Replies
    1. i second that idea

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    2. Brilliant idea and brilliant blog. Thank you

      Delete
  4. I think efficacy of administration is very important , especially if you are working. It's much easier to take a week off work, or a few days once a year with work colleagues being none the wiser than to take a day a month off. If successful, alem also lets you forget that you've got MS, you don't have to plan around your hospital visit. I know you have to have monthly blood tests, but you don't have to book them in with the hospital, just turn up.

    ReplyDelete
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    1. Re: "I know you have to have monthly blood tests, but you don't have to book them in with the hospital, just turn up."

      Yes, we are trying to arrange flexible monitoring system to suit your lifestyle. I agree that a yearly course of infusions has an advantage.

      Delete
  5. Yes, I do have one, probably too complicated for my diseased mind :) Where does this fit in other DMTs? (or where do other DMT's fit in this decision-making matrix?). Is it age? or the stage of MS you find a patient in?

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    1. Re: "Where does this fit in other DMTs?"

      This post painted a picture for two MSers with rapidly-evolving severe MS or RES-MS. In the UK natalizumab has a license for RES-MS. However, alemtuzumab has a license for active MS in adult MSers as defined clinically or on MRI. Therefore alemtuzumab can be offered as a first-line DMT to many more MSers than natalizumab. This post simply addressed the situation when there is a choice between these two drugs.

      Delete
    2. I see. Thank you for your answer. So the criterium is the severity and how fast the MS evolves. Now I have more studying to do on how to differentiate between different forms on a timescale.
      Regards

      Delete
  6. "This is why true patient-decision making may also be an unrealistic expectation."

    So what recommendation would you make to the two patients you described?

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  7. I think the swings and roundabouts of both mean that only a patient can make the decision. Which risks do you prefer? It will depend on your life circumstances and world view; when both options are imperfect it HAS to be the choice of the individual. Question is as above: what are the other autoimmunities possible, and how serious are they, how common are they? Thyroid issues are nothing to worry about, but what about the rest. We'll be monitored for ITP which is treatable, but what about Goodpasture's and anything else that might be in Pandora's box? Thank you for addressing this directly, there's a veritable vacuum of digestible information out there.


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  8. This is interesting and helpful, thank you, but I am not sure to whom it applies. It is surprising that the most potent treatment appears to be more available to all with 'active' MS. But how 'active' does your MS have to be to get treatment? Does 'smouldering' MS qualify? A bit of leg weakness-getting worse, but good mobility, a bit wobbly and some falls, but fully functional, very fatigued but able to work, lots of sensory problems and pain but able to cope. All progressing but no dramatics and definitely not RES. Is that 'active' enough or is it not severe enough for such drastic treatment? Why do some neurologists monitor activity with MRI and others say it is meaningless? How do you know if worsening symptoms are 'active' and not just progressive MS. Maybe 1st line DMTs are controlling relapses but not the progression. I remain confused. Just how 'bad' do you have to be to get treatment?
    Many thanks for these blogs and updates. I sometimes feel that I don't have 'real' MS as it is not RES and that I don't have the right to ask for info/MRI/more treatment as others are so much worse off.

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  9. I agree with sue a. I have the symptoms she describes, plus a tremor in my dominant hand. With no reviews how do we know whether such symptoms are active or progressive? Sometimes it feels as though a neuro diagnoses spms so it can then be decreed that there is currently no treatment for this condition - easy way out.

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  10. Thank you for all of your work for MS. Currently on Tysabri 14 months, Last 3 infusions I seem to starting with possible neutalising antibodies 12 hours after (Same as what I had while on Avonex). Would it be worth going onto natalizutumab? Thanks Tracy ex SA

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  11. Gosh, I so need a comparison table like that for alemtuzumab/anti CD20/ BMT! Natalizumab is out of the question because of JCV antibodies.

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  12. With the situation being further complicated (but hugely good news) by the emergence of Ocrelzumab will the question for potential Alemtuzumab candidates be, " Shall I wait until NICE approve?" rather than risk side effects from Alemtuzumab?

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    1. time is brain it will be 1-2 years before NICE approve i suspect.
      Therefore you have to think what can happen in two years one devastating attack that leaves you disabled and you may kick yourself. you need to plan for the here and now. In two years something better than ocreluzimab arrives do you keep waiting. This is your choice.

      Delete
    2. time is brain it will be 1-2 years before NICE approve i suspect.
      Therefore you have to think what can happen in two years one devastating attack that leaves you disabled and you may kick yourself. you need to plan for the here and now. In two years something better than ocreluzimab arrives do you keep waiting. This is your choice.

      Delete
  13. I am seeing my MS Nurse on Monday. Diagnosed in 2013 at the age of 55 and not offered anything at all. Last time I asked, the consultant said "when you want it" and I could have "what I wanted". No advice given. Since then, lots of reading - including this blog - and I am hoping I have some clarity. But I believe I shouldnt wait any longer to push for some help. Thank you for your blog.

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  14. I am going through this Exact scenario. I am 52 ms for 30 years but just this year getting worse. I know that O is too far off. I want to live, I want hope. To me after much research Lemtrada is hope, no matter the risks, Ty is giving up and has terrible risks and the future.
    After researching, there is no comparison to me.

    ReplyDelete

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