Confessions of an ECTRIMS fellow: what I really learned during my BartsMS fellowship

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As you might have captured in one of my preceding blog posts, I’m relatively new to the MS research blog. There is a logical explanation for this: I only started to work at BartsMS in November 2019. With the purpose of converting me in an MS-ologist, I was one of the fortunate people to receive a clinical fellowship grant from the European MS association ‘ECTRIMS’.  

The preceding ten months, I had the privilege to participate in the MS clinics of the BartsMS team. This has resulted in many new insights when it comes to the mode of action of the available disease-modifying therapies (= B versus T cells), treatment strategies (= escalation versus induction approach), COVID-19 readiness and – partially against my will – NHS England eligibility criteria for MS disease-modifying treatments. Although I’m happy to be aware of all these important treatment aspects, I must admit that they play the second fiddle when I offer therapies to pwMS. 

As I have been able to judge from the front line (read: behind my laptop camera as all our clinics are remote nowadays), people with MS in the first place want to leave the ‘kingdom of the sick’ and some drugs are clearly better at this than others. To summarize my impressions, I have made a radar chart of all currently available therapies: 

The axes of the chart range from 0 to 1, with 0 being a very low score and 1 being an exceptionally high score. 

A little word on the categories I selected:

  • Family planning: The majority of people with MS are women of fertile age. Therefore, treatments that you may continue while trying to conceive and/or during pregnancy as well as treatments that you only take temporarily and allow carefree family planning afterwards score high in this category. One of the most daunting MS relapses are the ones that happen in the three months after a woman with MS has given birth. Treatments that protect women with MS during this vulnerable period in life equally score high. 
  • Side effects: Side effects, especially when causing daily discomfort, unwillingly remind and confront pwMS every day of having the disease. This is especially difficult to tolerate for pwMS as they often feel perfectly fine between relapses. Treatments that have this kind of ubiquitous daily presence will score low in this category. 
  • Vaccination: Especially relevant during COVID-19 times and for people with MS that are already longing to venture around the world again. Treatments that allow you to have conjugate and live vaccines during or after completing the full treatment course score high in this category. FYI: Live vaccines are necessary to travel to many countries in Africa and South America. 
  • Convenience: Drugs that you need to take or inject on a daily basis score low while treatments that you need only once every couple of months/years score high. 
  • Efficacy: The ability of a drug to avoid new MS relapses and thus the interference of such unpredictable symptoms with daily life, work and leisure is priceless. Drugs that are more effective at controlling disease activity will score higher in this category. 

As you might notice when looking carefully at my graph, there is an important treatment paradox in the MS landscape. Treatments with lower efficacies in terms of reducing relapses which are typically grouped as ‘first-line drugs’ require a higher tolerance for side effects of the pwMS that are using them. Conversely, treatments that are considered highly effective (e.g. Tysabri, Mavenclad, Ocrevus) have a much lower burden to pwMS than what would be expected from their potential to control disease activity. 

Obviously, this graph is a simplification of treatment decisions in MS and many more aspects such as for example the risk of progressive multifocal leukoencephalopathy need to be taken into account. However, I feel these patient-centred aspects of treatment strategies are underrepresented in discussions on this topic and especially in the current NHS England eligibility criteria for disease modifying drugs

In conclusion, instead of converting the MS treatment landscape into a war zone of conservatives versus liberals, hawks versus doves and doers versus thinkers, the real question that we as neurologists need to discuss is how we use our treatment arsenal to enable pwMS making peace with their disease. 

About the author

Ide Smets

28 comments

  • Ide,

    The graphic is excellent, thank you,. I stand to be corrected but isn’t HSCT a viable NHS funded option in some cases? If the plot is viewed over time and has cost/benefit factored in I wonder how much and if it would change.

    Thoughts?

    Thank you,

    • Yes, you are right about HSCT, but I left it out as it is only offered as a third-line therapy in the NHS and not relevant for the majority of the people (+ currently on hold given COVID-19). Anyhow, it would not score well on convenience 🙂
      It would definitely be interesting to look into the costs of these products and see how it links up with the NHS England approval policy. I expect the first-line therapies to be more expensive in the long term as people often stay on them for a considerable amount of time.

      • I guess what I am driving at iis that – purely from a financial perspective – the NHS is missing a trick with regards to the increased costs of a patient deteriorating sooner and costing more overall as a result. QUALYs and all that.

        More importantly is the patient perspective and my view (as a patient) that I want a neurologist to be treating me with as view for me 20y hence. Not gentle back patting now.

        It ties into the Papa Smurf post earlier today. I think that patients risk tolerance is much higher if things were put in a long-term context.

        Thanks again for the great graphic. Are you ok of I use it in the future providing it is attributed?

        Dominic

        • I think first-line therapies are not cost-effective in many ways: the cost of taking the drug long-term, the cost of absenteeism at work etc. because of continuous side effects, and the costs induced by disability accrual/low QALY’s.
          I would not say the long-term perspective is that important for everyone. From my experience, many people seem to be driven mainly by short-term convenience (what I totally understand). But the good thing is that those two viewpoints do not have to contradict each other when using high-efficacy therapies.
          Feel free to use the graph, and keep me posted on the feedback.

          • I wonder if the short tetmism is driven by old practices? The fact that therapies have changed faster than attitudes may be part of it. Previously it was just welcome to the Kingdom. We’ll be there for you as the disease robs you of ability.

            If all the discussions had an element of, ‘ this is a long game’ wrt treating to reduce frequency and severity of the decline along with the treatment of symptoms, I wonder if patients would also look ahead more.

            The doctor is SO influential, especially when newly diagnosed and utterly discombobulated. The lead comes from the HCPs, especially when patients are bombarded with so much trash online.

            And yes, if used I will report. Thank you.

  • Thanks Ida, I love this graphic! It is a great visual to help understand where the compromises have to be and is spot on for my priorities and choice of DMT. I can see lots of people plotting themselves on it in future and using it to guide their decisions.

    This clearly shows why different PwMS make different choices and I commend this patient centred approach.

    I am interested though (as a non-scientist) – why did you pick scores from 0 to 1, rather than say 0-10? Is it just the idea that 0.1/0.2 etc is a part, whilst 1 is a whole thing and you can’t get better than that?

    • Thank you! About your 0/1 versus 0/10 question: I have no comprehensive answer. I think powerpoint suggested this axis range 🙂 But you are right, maybe it’s better to put it on a scale from 0 to 10.

      • I see Lentrada as the the one with more efficacy, also the side effect don’t look that bad, but what I understood was that secondary side effects make it a difficult drug to manage. I s Lentrada a good choice if you want to have a family

        • Personally, I think Lemtrada is a relatively good choice when family planning but you need to have completed both courses of the treatment and then wait for at least 4 months. The good thing is that thereafter you can freely decided about family planning.

  • Thanks, this is quite enlightening.

    Tho I am a bit surprised by natalizumab vs ocrelizumab – both on efficacy and especially side effects (think PML risk) the ranking does not really fit my interpretation of the data I’ve and what I’ve been told by neuros… Would love to hear your rationale!

    • My graph is my interpretation from the data, so definitely no exact science. The reason I gave natalizumab a slightly higher score in terms of efficacy than ocrelizumab is because it starts working faster. Natalizumab works almost immediately after the first infusion while ocrelizumab needs a couple of weeks/months to be fully active against the disease.
      The PML risk was a tricky one to integrate in the graph because when the current risk mitigating strategies are correctly put in place it has become very rare for pwMS on natalizumab to actually develop PML. So this is a side effect that we are effectively able to prevent and should therefore, in my opinion, not have too much weight when deciding on DMT strategy. Moreover, it’s only relevant to people that are JC-positive. When being JC-negative, the PML risk is almost zero. However, I do acknowledge that when developing PML, the consequences are devastating and the graph thus only applies to centres that have their natalizumab/PML monitoring up and running effectively.

      • Very well explained, thanks a lot.

        I wish the treatment ‘lag’ with ocrelizumab was explained to patients better. I had sort of suspected it after reading the Opera paper (otherwise why rebaseline) but nobody told me upfront. Now that I went to get a second opinion because I am less than happy after first two cycles the second neuro was like: ‘but what you describe is not uncommon for the first few months of ocrelizumab’.

        • Yes, I understand. It’s always difficult how much information you give as a neurologist when guiding your patients and it really also depends on each individual how much they want to know but would have been relevant in your case.

  • i for one think this is great! however its such a shame that treatment criteria has to be taken into account its a very sad situation when someone diagnosed with a lifetime degenerative disease has to fit “criteria” to be treated with the strongest available option no matter if it is more cost effective or not i dont think the nhs and nice should have input should be purely a patient and treating physician decision. i dont think someone with cancer would wait until they are worse for a stronger drug…. when my mum had breast cancer they done what they needed to do no jumping through hoops to qualify for treatments.

    • Thanks for your reflections. Personally, I think it is logic that there is a sort of regulating body when it comes to approving MS drugs as they are very expensive. However, I totally agree that this watch-and-wait how-aggressive-the-disease-is policy of the NHS is not ethical and should be curtailed sooner better than later. Unfortunately, I have to add that this is not only true for the NHS but also the reality in many other European countries.

  • Clarification please as to why Mavenclad scores highest in terms of side effects (am I interpreting that correctly)? Higher then alemtuzumsb (secondary autoimmunity), ocrevus (malignancy risk, immunoglobulin deficiency).

  • Excellent graphic. Thank you Ide. I’m still not sure about NICE’s criteria. Is it that they prefer practitioners to offer least effective effective DMDs first, forcing them to adopt the escalation model? Despite having only been diagnosed 16 years ago, I know I’ve had MS since at least 1988, maybe even the sixties, having had weird stuff going on in my teens. I’ve never taken anything, but now PIRA has come to my attention, maybe I should. I’m returning to my original neurology dept., as it’s HOD is closely associated with BARTS and drew up “Brain Health” with Prof G et al. My current dept. can’t allow me an MRI even if I pay for it. Hoping that I can figure out what option is best for me as I don’t fancy losing more brain volume than the gen. pop. any more. On the other hand everything points to treatments being less effective in the >70s. This graph is really useful as I make up my mind. But will I be eligible..?

    • Thank you Kit! I do not know your case but overall it is safe to say that to be eligible for treatment your neurologist would have to demonstrate convincing clinical/MRI (or CSF) evidence of inflammatory disease activity and this sort of activity becomes indeed more rare in advanced disease stages. Success with your appointment!

      • Thanks for the guidance. I’m so well, still running and swimming daily . That what’s unclear. I may be NEDA or there may be inflammation. How is brain volume loss measured in pwMS?. Will find some of it out inMRI next month.

        • Nice to hear you are doing well! Brain volume loss is not routinely measured in our clinical practice. Due to technical issues, this is currently only done in a clinical trial setting.

  • Interesting graphic and a great tool for individuals newly diagnosed. However, one significant factor is missing……i.e. the severity of the side effects. Your statement, “Conversely, treatments that are considered highly effective (e.g. Tysabri, Mavenclad, Ocrevus) have a much lower burden to pwMS than what would be expected from their potential to control disease activity.” I agree; however, the adverse side effects of the highly effective DMTs are much more serious than those of the lower efficacy group. With high efficacy comes higher risks, this relationship must be discussed, even with current derisking strategies. While the probability of serious adverse side effects is generally low with the high efficacy group, if one is unfortunate enough to experience these side effects, they can be devastating and long lasting. I speak from my own experience. Plus, I flipped the pyramid and had adverse side effects and breakthrough disease activity, so now I am left with very few options and very little data/research to guide my next steps. Thankfully I have this blog and the amazing group of pwMS who share their comments, thoughts, experiences, and sometimes their frustrations. 😉

    • Hi Tom,

      What treatment did you take and what were the reactions (if you are kind enough to share)?

      I think some people on the blog mentioned feeling fatugued and balance issues getting worse after Ocrevus (at least for a few weeks after treatment)

    • Hi Tom! Thanks for your comment. You make a fair point there. This graph is only a first impression of my experience in clinic and therefore far from perfect. We are looking into how to expand it and convert it into a tool for pwMS. Then we’ll probably make the distinction between short and long term adverse events as well as general tolerability of the drug. TBC!

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