MS controversies in India

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Controversies in Neurology (CONy) launched about 15 years ago as an annual get together for neurologists to discuss topics where there is no single answer. And there are obviously many questions without a single answer in neurology just as in medicine as a whole. Over the years, CONy has become a fixture in the calendar of many of my colleagues. I co-chaired the MS section in March; here’s the programme:

Multiple-Sclerosis-1

Now, what I didn’t know until that meeting was over, is that there is an Indian spoke of CONy. CONy India met last weekend in Goa, and I was generously invited to debate the motion that people with MS “should be offered off-label immunotherapy when licensed disease modifying treatment is not available”.

I really wasn’t sure how colleagues would vote on this, but a whopping >80% were in favour even prior to exchanging any arguments, which I thought was great. However, knowing the rules of debate – it’s all about the swing vote – I felt some mild trepidation messing this one up. Even more so given my opponent was a highly decorated neurologist, Lieutenant-General and Honorary Surgeon to the President of India, Dr CS Narayanan. Here are my slides:

CONy_India_20220423_4_Blog

Reassuringly, and following some very well delivered points from the floor highlighting the extensive use of rituximab (and some azathioprine) to treat pwMS in India, about 90% voted in favour of the motion.

If you’re interested in access to healthcare, particularly immunotherapies, for pwMS in LMICs, I suggest you visit the MSIF’s website and scroll to the MSIF Off-Label Treatments (MOLT) panel’s guidelines covering azathioprine and rituximab. Public consultation on these has just closed, but it’s encouraging colleagues are putting pwMS first, doing what is biologically (and IMO ethically) the right thing to do when there are no equivalent or licensed options.

MSIF_4_Blog_20220427

I guess some of you may be wondering did he travel all the way to Goa to win a debate, and the answer is no, despite respective invitation, the attraction of balmy 33°C, no doubt wonderful food and F2F conversations with colleagues. I rather set myself up at home facing the garden (13°C), saving the planet my share of 2.25 tonnes CO2 emissions and absolving myself – on this occasion – from hypocrisy.

Disclaimer: The opinions expressed on this Blog are those of the author and nobody else.

@KlausSchmierer

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23 comments

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  • Thanks Prof K, brilliant post and fantastic slides! My favourites:
    Slide 3 MS is a bad disease
    Slide 24 comparison dmt costs
    Slide 37 repurposing Pharma style

    Encouraging to learn extensive use of off-label dmt worldwide (where appropriate ie no effective / affordable licensed tx available), 80% in favour increased to 90% after debate. From your slides amazed wasn’t 100%!

    Also great to see MSIF off-label guidelines recommending rituximab as first line tx. On WHO essential medicines list too 🙂
    Pity cladribine sc not also investigated!

    • Thanks Annonie. Cladribine has been a 6-year journey getting to ChariotMS, I doubt it’ll ever make it on the WHO list since its use in conditions other than MS is far less common than for RTX and AZA.

  • So the other side of the argument would be…pwms should not be offered off label immunotherapies when approved DMTs are not available. The neuros in India would be comfortable to see their patients progress without treatment? I don’t see how this could be defended. It is 2022 not 1982.

  • “Life expectancy reduced by 5-10 years”
    “7.5x greater suicide rate than the general population”
    + it appears that MSers who get to EDSS 8 and 9 have a negative quality of life ie they’d prefer to be dead!

    Unsurprising that MSers get depressed!

    Are any of these figures actually changing given the very expensive MS treatments that have been available since the mid-1990s (and highly effective treatments since the mid-2000s (Natalizumab))?

    Thanks for your concern about the environment.

    • Good questions, and yes these figures are changing. I always hasten to say these are by in large pre-DMT figures, though some (e.g. the divorce rate) are more recent.

  • Ironic that MS patients in poor countries getting rituximab and cladribine at diagnosis will probably do much better than patients in rich countries getting expensive but fairly useless platform therapies first line.

    • Had exact same thought Anon and doubly ironic when looking at the excellent slides ProfK used to underpin ‘vote yes’ in the debate.

  • Is anyone in India getting cladribine off-label? I don’t know of any cases.

    Here are some of the complexities for Multiple Sclerosis in India –
    – neurologists are overloaded and MS patients are a very small subset of the patient load
    – some treatments are not licensed in India
    – the cost of treatment is exorbitant as compared to what people earn
    – everyone does not have medical insurance, but medical insurance isn’t much use even if you have it. The claim limits are too low compared to the cost of MS treatments, and medical insurance covers only inpatient bills (with a minimum admission of 24 hours. The insurance companies do question whether a 24-hour hospitalisation was justified)

    • I did not ask the question regarding cladribine; the debate was about off-label treatment which is addressing exactly the point you’re making which is cost. I use Cladribine as an example since we have some experience with it published over the years and since its bioequivalent with Mavenclad. The reason colleagues in neurology have generally little experience with it is due to its limited indications outside hairy cell leukaemia. People are more familiar with Rituximab and Azathioprine because both are being used in a range of indications. The MSIF’s MOLT panel therefore quite rightly focused on these two.

  • Hi prof K,
    which plan would you favor for someone newly diagnosed with spinal cord and brain lesions?

    a) 2, 3 courses of clad then watchful;
    b) Rituximab/Ocrelizumab before new drug.

    Thank you!

    • For immediate treatment I’d favour natalizumab. This is the approach we’re testing in AttackMS (https://multiple-sclerosis-research.org/2022/01/attackms/) and has the advantage of being ‘non-committal’ (there are sometimes diagnostic uncertainties in the very early days and people hesitant to give something with long-term effects). After that, both IRTs and regular B-cell depleters have their pros and cons.

      • What do you say to 2 courses of cladribine after years of rituximab/ocrelizumab?

        The rituximab has done a good job. Can cladribine be a way to stop the regular B-cell depletion?

        Has this been tried? Is there any information on possible problems and effectiveness?

        • ANONYMOUS – I am a not aware of any formal studies or guidance on this topic; however, it is documented in the prescribing information that not all pwms will repopulate after one or two course of Clad. I am in that group. So essentially, the effects of Clad b my immune system my be permanent.

          For background, I stopped OCR after four course (severe adverse reaction) and switched to Clad. I am 11 months post year one of clad and my B cells remain well below my base line levels. Total lymphocytes remain slightly below 900, and my red/white blood cells remain below baseline levels. Starting year 2 of Clad in 1 month.

          I have theorized that because of ORC being use first, then Clad, my B cells may never recover to baseline levels.

          This may be good from a disease activity stand point (long term depletion of memory B cells) but bad from an increase susceptibility to infection.

          All very confusion and not a lot of research on this topic. Hope my experience provides some clarity.

          • Thank you for sharing your experience.
            “Will never recover” sounds rather extreme and unlikely. Perhaps they will take longer to recover: 11 months isn’t all that long

        • We should have some data on this issue rather soon. What I can say is people have switched from B cell depletion to cladribine as a way to avoid ever recurrent treatment, and I am not aware of specific adverse problems, though it is well possible that already long-lasting B cell depletion is further extended (and potentially more pronounced).

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