46 Comments
Sep 25, 2021Liked by Gavin Giovannoni

I’ve found this newsletter really depressing as I’m one of those people who wasn’t prescribed a DMT for several years. I wasn’t having relapses, but I did have optic neuritis on one occasion. (at 40) So now here I am at 64 - I’ve been told that there’s no point in taking Tecfidera anymore- my latest MRI shows that the ms is inactive (doesn’t feel like that!) So no other option but to wait until I shuffle off this mortal coil! I’m usually a very optimistic person but it’s hard to remain so, when your options are so limited. 😢

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Sep 26, 2021Liked by Gavin Giovannoni

@Lynn I have ot reply because you sound like an amusing, ironic companion and I hate to think of you 'waiting to shuffle off.' I know what you mean by it doesn't feel inactive even if it's called that (some people informally call mine benign, thanks) and I don't share your feeling of missing out on DMTs but I do get how it might feel like that. But doesn't Prof G calling exercise potentially a DMT give any hope? I do online MSGym on zoom every morning with a buddy group (join ours! 0845 am) and it's apparently geared to neuroplasticity as well as physical strengthening, flexibility and endurance. I know my body better than I ever have anywayand enjoy doing it most of the time, plus there's a support aspect with ppl who understand. There's also a linked huge international community of ppl with all levels of impact of MS some of whom have had remarkable results and always ready to answer questions. It works out about £1 a day and since a revamp recently is really worth it to me. And don't get me started on how happy I am with the the super-healthy OvercomingMS diet (I would guess another potential DMT.) I sound like Pollyanna here but there does seem to be a value in taking action in itself. Good luck anyway.

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Sep 26, 2021Liked by Gavin Giovannoni

Kate, Thanks for your reply. I do some of the ms gym too, but I’m only on my second cuppa by 8.45! I’m in Buckinghamshire and am lucky to have the Chiltern ms centre nearby, so also do some of their online exercise classes. I live by the mantra use it or lose it, so onwards and upwards…… 👍

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So interesting to read this thread - I am considering the MSGym...8.45 might not work for me either as I am working at that time (some days)...also a member of CMSC, thanks for the very positive post

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@Bluebird really recommend doing it with a buddy group, there's info from the start about how to join or start one

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Thank you - that's one of the attractions :-)

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Sep 26, 2021Liked by Gavin Giovannoni

My experience is so similar to yours, even down to age...

Like you I feel there's so little we can do to help matters, despite wanting to. Which is one reason I asked the original question (what more can people in our situaition do?)

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Sep 26, 2021Liked by Gavin Giovannoni

I have hydrotherapy once a week, which although expensive, I find incredibly helpful. It’s just amazing that there are so many drugs for relapsing ms but nothing for SPMS! Maybe they will come up with something in the next few years 🤞

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Sep 25, 2021Liked by Gavin Giovannoni

I am in a similar situation to Kit, previous poster, except that I have requested siponomid, have had mri and am awaiting appointment. Had 2 relapses in 20s, nothing for 30 years but SPMS diagnosed in 50s as slowly deteriorating. What more can people in our situation do (also volunteer for trials, most recently Sizomus)? Feel I missed the boat in terms of DMTs because of timing!

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Sep 25, 2021Liked by Gavin Giovannoni

Given what we know now watchful waiting (with very rare exception) should be considered malpractice

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Sep 25, 2021Liked by Gavin Giovannoni

This is a timely and useful series of questions and answers. I do wonder about “ageism” though.

When you say you don’t “agree with this,” are you referring to a) denial of treatment given the current state of knowledge, b) arbitrary denial based on age alone, or c) the scarcity of RCTs investigating the use of DMTs in older pwMS?

I’m 71 and use a wheelchair (EDSS ~7.5). I was diagnosed with MS at age 55 and free of disability until 60 - waiting under watch, I suppose. I was then on glatiramer acetate for 18 months, followed by natalizumab for 12 months, until a JCV test came back positive. My neurologist, a 25-year MS specialist whom I greatly respect, believes that for me the known risks of leading-edge DMTs outweigh the hypothetical but undocumented benefits. In the case of ocrelizumab, and presumably other lymphocyte-lowering drugs, she considers the risk of infection to be unacceptably high given the high likelihood that it would aggravate MS symptoms and worsen disability. Among factors that make it impossible to draw conclusions about efficacy, she cites the age-55 cutoff in pre-approval ocrelizumab clinical trials.

I don’t see her position as ageist. As far as I can tell, here in Canada very few pwMS over 60 and almost none over 70 are on a DMT. The only ones in use among this group that I’ve heard of are glatiramer and the beta-interferons. Of course this may be a function of payer policies, and it certainly reflects the state of knowledge about DMT efficacy in older pwMS. But is the age-55 cutoff common in DMT studies itself ageist, or are investigators simply trying to sculpt a population conducive to favourable results?

I don’t consider myself risk-averse. I do everything I can to preserve strength and function. I’d love to augment that with a DMT. But I’ve had two systemic infections that led to rapid significant irreversible decline and I have no desire to repeat the experience.

If I’d known what we know now I might have pushed for treatment when I was almost symptom-free. But then, at the time, only the first-wave DMTs were available - the ones now considered low-efficacy. So am I a victim of ageism, or have I been just a bit too old all along?

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Re: "a) denial of treatment given the current state of knowledge, b) arbitrary denial based on age alone, or c) the scarcity of RCTs investigating the use of DMTs in older pwMS?"

All three. The assumption that DMTs don't work after about 54 years of age is compounded by disability and using the EDSS as an outcome measure in trials. Older people with MS who are disabled and have active MS still have their upper limb and bulbar function to protect. We shouldn't write them off. And yes, we should be doing clinical trials in older people with MS; setting age cut-offs for eligibility for trials means we don't have enough knowledge about how older people with MS do on these DMTs and more importantly their safety profile in this population who are more likey to experience adverse events.

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Sep 26, 2021Liked by Gavin Giovannoni

Wonderful. Thanks for challenging orthodoxy and complacency. Too many >50y pwMS are adrift with scant follow-up in clinic and little guidance about what the future may hold.

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Sep 27, 2021Liked by Gavin Giovannoni

Hello Paul. I was wondering if it could be that dealing with people for whom the outlook is pretty bleak is just too much for some doctors to deal with. Many aspects of medicine result in a cure or improve a condition (even RRMS is becoming more hopeful as research continues), whereas as one ages, MS treatments do not. Eve

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Oct 4, 2021Liked by Gavin Giovannoni

I think you’re right, Eve.

Apparently the catchphrase, back when MS was a real mystery and there were no treatments to speak of, was “diagnose and adios.” My ex-GP said all her chronic patients knew more about their diseases than she did. Even neurologists, I suspect, become jaded - a recently published study here in Canada identified “treatment inertia” as a challenge for MSologists.

But there are many reasons for hope, and fresh opportunities for practicing real medicine among the older MS community. As Prof G has said repeatedly, the boundaries around DMT use need to be breached. Clinicians can contribute to this through advocacy, either publicly or behind the scenes.

For me, however, the most important frontiers right now are physical therapy, mental health and lifestyle adjustment. We’re starting to get studies on exercise led by physiotherapists with doctorates and research appointments. We need much more of this. It’s not enough to compare resistance training with cardio, or try to show that cheap tele-therapy is just as good as the real thing.

We need to know, for example, what precise combination of onabotulinum toxin injections, muscle relaxants, specific weight-bearing exercises and stretches, hydrotherapy, nutritional approach and supplements is optimal for MS spasticity - the #2 symptom after fatigue in many surveys — in a given patient. Without research leading to detailed treatment guidelines, even the best clinicians default to treating what they see without delving into the pathology underlying symptoms, which as we know is unique to each patient.

To do this work and to attract the funds for it, a reconsideration of what constitutes relevant evidence may be required. Conventional hierarchies of evidence privilege quantification and bias reduction through randomization, controls and blinding, but these may not be achievable at ideal levels where physical therapy, patient self-reporting and clinician estimates are involved. Methods can always be made more rigorous, but research questions must not be whittled down toward irrelevance in pursuit of conformity to standards developed for different fields of inquiry.

At present, vast quantities of published data about the course of MS in individual patients and their therapeutic experiences are absent from the systematic review literature on which resource allocation depends. If this information had been recorded in narrative form and stored in archives it would be regarded as invaluable treasure by medical historians and other qualitative researchers. Because it’s generated and published in the universe of evidence-based medicine, the studies are dismissed as statistically underpowered, the data as vague or subjective and the quality of evidence low.

Front-line clinicians, including GPs, neurologists, physiatrists, nurses and physiotherapists, see the effects of CNS disease in the bodies of pwMS every day. Unquestionably the experience can be discouraging, for some even overwhelming. But they have real-world experience that is not being captured in ways conducive to informing policy and resource allocation decisions. Perhaps rather than succumb to disillusion they might develop ways of codifying the supposedly subjective knowledge they and their patients accumulate to give it a chance of being influential, in quantity and organized.

Thanks for the prompt, and to MS Selfie for the space.

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OMG! I was in my mid 50's when i was dx'd! I hardly feel that i should have been written off at that point because i was that "OLD". I am 63 now but i have had some serious side effects with Mayzent which i just came off of a couple of months ago. i am now SPMS but the disease is very much active. I am getting results of new MRI done a couple days ago when i see Doc on Monday. I expect it to be bad. both brain and neck. UGH.. with the reaction i had to Mayzent and also having had 2 relapses in a year while on it, IDK what we are going to be looking at. I am thinking of asking for Aubagio or something that will not lower my white counts so drastically the Mayzent did.. It was horrible.

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Re: "I don’t see her position as ageist. As far as I can tell, here in Canada very few pwMS over 60 and almost none over 70 are on a DMT."

I suspect you don't have any overt ongoing disease activity and hence her position is very appropriate. It may change, however, you had a brainstem relapse with a new active lesion. This happens even in 70+-year-olds. At the end of the day we treat the disease when it is active; if it is inactive which happens with time we derisk patients and stop DMTs so as to not expose them to excess risk. I hope this makes sense

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Sep 26, 2021Liked by Gavin Giovannoni

Yes it does, thanks. It was the word “ageism” that I wanted to clarify.

I hope I don’t have to make any decisions following new EDA. I have my hands full with symptom management. I do quite a bit of exercise. Currently trying to persuade the Ontario health service to fund regular lower-limb botox to relieve excess tone, expand range of motion and boost the strengthening potential of weight-bearing movements. We desperately need evidence for choosing from the vast array of exercises available.

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Sep 26, 2021Liked by Gavin Giovannoni

Professor Giovannoni. May I ask what do you consider to be an appropriate length of time to 'watch and wait?'

In an individual who is experiencing symptoms of PPMS, do you 'start the clock' from when they first see you, or when they have the first symptoms? I see you constantly disagree with delaying treatment, yet it appears one can wait and wait, developing different symptoms, or the ones already present exacerbating, or even worsening exponentially. I understand (DM) treatment is not always suitable in some older people exhibiting symptoms, but surely some medication to help improve their quality of life is warranted?

Thank you for you and your team's tireless efforts.

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From first symptoms. The diagnosis relies on 6 to 12 months of worsening.

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Sep 27, 2021Liked by Gavin Giovannoni

Hello.Thank you very much for your reply. I am now over two years without a diagnosis, although 'all roads lead to Rome'. I, as others have said, feel 'invisible'. It must be difficult for a doctor in that situation, as he would be unable to make such a huge difference to my life, as he can with a young RRMS patient. If only he knew that just having relief of symptoms would improve my life dramatically. Thanks again. Eve.

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Most people with PPMS present with symptoms that go back several years. That is why it is difficult to find someone with PPMS who has been diagnosed with 1 year of symptom onset.

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Sep 25, 2021Liked by Gavin Giovannoni

Do you see any significance in late diagnosis? I was dx 2012 at 57 with only a moderate gait problem of a few years; told I 'shouldn't be in a wheelchair within 12 years,' whatever that meant. DMTs weren't prescribed and I was glad. Nearly 10 years later, I haven't had any relapses as such though fatigue has significantly increased and exercise endurance dropped; nordic walking poles improve my walking but I can also do without less far. I have been on Jelanek's OMS programme since dx and do online MSGym daily with a buddy group. I am about to have my first MRI since 2011 and will take your ideas to feedback discussion of a siponimod possibility. In your view I come into the risk averse category but in my mid-60s (average death for women is at 83) surely there is a cost/benefit balance for risks of any medication?

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Not sure your MS is active. I would only consider siponimod if you have disease activity. You are also an example of how exercise may be a DMT. Exercise is a remarkable thing and it stimulates many biological pathways that are thought to impact positively on MS outcomes. Keep exercising, but don't overdo it there is a sweet spot.

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Sep 25, 2021Liked by Gavin Giovannoni

I think we should consider a minor modification of the definition of inactive MS. If pwMS are on maintenance high efficacy treatments (*mods, natalizumab, ocrelizumab, rituximab, ofatumumab and so on), each with about an ARR of 0.1 then why we say 2 years to define inactive? I would say that it takes 20 years to say one has inactive disease with these drugs based on relapses or focal inflammation

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Sep 25, 2021Liked by Gavin Giovannoni

That what I concluded. Is there anything I can do? I receive my annual phone call next Monday (2 days time)? I only ever have one 10 minute call per year. I know how well I am, but there are always issues to address. My strategy is exercise which is probably as neuroprotective as meds and I am no longer on any other medication.

As you say a higher proportion of pwMS have certain co-morbidities and I did have depression twice, which I put down to MS as there's nothing in my make up which would predispose me to low mood otherwise. My consultant monitored me for nearly three years after I got better because he's an expemplary psychiatrist. Suggested I stick to medication for several year, but I took myself off everything last summer without medical help, as he's semi retired and the GPs were overwhelmed. I took 17 weeks to do it and it has worked well.

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Sep 25, 2021Liked by Gavin Giovannoni

I fall into more than one of these categories. To whit, age and NEDA. I’ve never been so offered any treatment. It’s not that I’m showing any symptoms but the one thing that is always on my mind is BVL. I reverted to my original neurology department when the one I attended would not even let me have an MRI when I offered to pay. I had been with that department 6 years and never been offered a scan. Now I have had one in 2020, the first since 2014 but am told I shan’t need another. It’s as if I don’t count. I know a low Tesla scanner can’t do much to I/D BVL but what ca I do to protect myself especially as my running days are over as far as my knees are concerned. I swim and gym as often as possible but I don’t have a clue how I’m actually doing. My neurologist is co-author of Brain Health; Time Matters and though we chatted at the Torquay MS Information Day, I don’t see him at my clinic. In fact I last saw an NHS consultant in 2004. The MS nurses are great but I am effectively invisible.

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Sep 26, 2021Liked by Gavin Giovannoni

Do you find neuro services in the SW accessible? (sounds maybe not)

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Sep 27, 2021Liked by Gavin Giovannoni

Not “horoscope”. I wrote something else. Stupid predictive spelling changed it.

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Sep 27, 2021Liked by Gavin Giovannoni

In the far SW. , yes. I transferred to another clinic in another county when my neurologist Prof Z moved to Scotland. To get straight on to it, I opted to pay to see the neurologist but never saw him subsequently. I saw an MSnurse annually for 3 years and then one annual phone call for 3 years. When I suggested an MRI last year I was told it would not be possible even if I paid, so I returned to my former NHS neurology department which could provide one. I’m ineligible for any treatment anyway. While living abroad just after diagnosis, I was referred to “…the best MS clinic in Europe.” It probably was judging by the extraordinarily intense full day I spent there but that’s another story. My MRI W

was59 euros and the gadolinium 72 euros with instant written report, verbal feedback and horoscope of my scan which I still have. My 1st and only visit to my replacement department, the MS nurse was fascinated to see my MS Plates as they aren’t allowed to see MRIs in England and Wales!!

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Thank you very much for this...not sure why you requested an MRI if you are ineligible for treatment anyway? Were you hoping somehing would be found that would mean you would be eligible?

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I need an MRI for comparison with earlier ones to monitor BVL. In any event, annual MRIs are considered good practice by many neuros. Aaron Boster is always going on about his patients having their annual MRI. My MS nurse agreed yesterday when she rang to carry out my annual check up. She has put in my notes that I'm OK with having a scan less than once a year, but that I would like one in 2-3 years. My last 2 were 6 years apart and show no brain atrophy, but that might change. Also scanners will get better and be of higher resolution as time passes, enabling more data to be harvested from higher tesla machines in the future.

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All good reasons to request one :-) good that you have an MS nurse and that she is putting you forward for the scans you request

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I think you may be a victim of an under-resourced NHS.

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This is not an excuse, but the harsh reality of what most of us have come to accept living in the UK. This is why I am slowly becoming more political. Who knows my next role in life may that as a healthcare politician.

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Sep 25, 2021Liked by Gavin Giovannoni

We need people like you in politics- so please seriously consider it!

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yes, we do!!

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Not general politics, health politics, possibly working for a non-governmental.

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Sep 26, 2021Liked by Gavin Giovannoni

I understand that through successive governments the NHS may be under-resourced, but please do not exclude one of the reasons being that consultants and GP's are now working part-time because their tax bills would be too high, due to their pensions and increased salaries. The NHS needs reorganisation. I know, I used to work in the organisation and witnessed much waste, and under- resourcing of equipment and staff.

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Sep 26, 2021Liked by Gavin Giovannoni

Each year since 2010, the NHS had only one quarter of its average annual increase for its whole lifetime. So the guff about 'biggest funding increase in its lifetime' recently is meaningless after 10 years of that. Yes I've worked in it too and it has its faults but the only reason it is even still doing any patient work is the dedication and going the extra mile of clinical staff and i believe that is at all levels. That and the parts still a public service, it s just a different ethos and the time and motion managerial types and their internal market just don't get anyone doing anything for anything but money.

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Aug 29, 2022Liked by Gavin Giovannoni

I am not eligible for any treatment and manage m MS through diet (OMS programme), regular exercise, physical therapy (Dr Gretchen Hawley) and meditation. I have inactivity on my MRI and. My Neuro is very much a ‘watch and wait’ kind of Doctor. I have not had a relapse ever and live a clean life. I have tried to swap my Neurologist bur wasn’t allowed. I just keep ticking along.

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All sounds good. In my clinic, in the NHS, you would not be eligible for DMTs either. We would also be watching and waiting to see if your MS remains inactive or becomes active and would trigger a review to offer you a DMT.

Please note on the NHS we can only treat active MS. Contrary to many peoples' expectations I don't have every patient with MS in my clinic on a DMT. I estimate that about 30% (3 out of 10) patients are not a DMT for this reason.

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Nov 28, 2021Liked by Gavin Giovannoni

Hi Prof G

I've just re-read this excellent article, 2 months on. As someone currently on a "Wait & See" treatment plan, and having observed numerous posts on MS forums, I am concerned that overstretched MS Teams are using W.A.S. as an opportunity to either buy themselves some time or abdicate from the responsibility of making a diagnosis. It is appreciated that to someone on the inside of "the system" such a suggestion would be seen as inflammatory, but perhaps it might warrant a review of the reasons why W.A.S. is at times. a valid medical approach in MS treatment?

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Graeme, thanks for this. Yes, I will write an MS-Selfie Newsletter on 'Wait-and-See' or as I prefer to call it 'Watchful Waiting'. Yes, I think there are circumstances when this may be necessary and justified in the management of MS.

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Thank you. However, I would take issue with the word watchful. To patients being kept at arms length by zoom consults, no email addresses volunteered and "leave a message and we will try to respond within 2 days" for phone calls, it feels more like kicking the can down the road rather than a suggestion of attentiveness. Not all Neurology Departments are the same...

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Sep 26, 2021Liked by Gavin Giovannoni

What another interesting article . I have SPMS for about 5 yrs . MS diagnosed 1992. Would you advise the use of DMT’s in what they call benign or inactive Ms Professor?

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