The first is a patient with quite advanced MS who was reasonably well controlled on fingolimod. She moved to London to join her husband from a European country. She, unfortunately, ran out of fingolimod tablets before seeing me and by the time she arrived in our service she had rebound disease activity with severe brainstem and spinal cord disease activity. She was off her feet with the loss of bowel and bladder function.
The second case was also a European who has been living in the UK for 10 years. His first attack was a brainstem attack that occurred almost 2 years ago. He was initially seen in accident and emergency department of a district hospital. It took him almost a year to see a neurologist and then 6 months for a diagnostic workup to be completed before being referred to me. It took me just shy of 3 months to see him in my new patient MS clinic. By the time I saw him it was 21 months since he had his initial attack. His EDSS was 4.5. He now has bladder and bowel problems, unsteadiness of gait, double vision, weakness in his legs, incoordination in his limbs and depression. He has also lost his job and is unlikely to be able to resume work. His MRI is a full house of poor prognostic factors; high lesion load, Gd-enhancing lesions, posterior fossa and spinal cord lesions, black holes on T1 imaging and some early brain atrophy.
What did we do? We have put both these patients on natalizumab as part of our #BrainAttack paradigm, i.e. to get on top of the MS disease activity before we even have their JCV serostatus back. If they turn out to be JCV positive we can derisk their PML risk, by switching their treatment or offering them extended interval dosing (EID).
All MSologists have patients who have had catastrophic relapses whilst waiting for a diagnostic workup and/or DMTs. We also know that MS activity tends to be clustered, i.e. one of the best predictors of a relapse is a recent relapse. Instead of putting patients with possible early symptomatic MS at risk from having to wait why don’t we to treat them all with natalizumab to protect their brains and spinal cords? This is analogous to treating stroke.
Why natalizumab? It is one of our most effective DMTs, it works very quickly, it is given as an IV infusion, hence there is no problem with adherence and is very safe for up to 12 months. It is also relatively safe in pregnancy. During this 12 month period, the neurologist and the patient can then decide what strategy they want to pursue in the long-term. This could be to continue natalizumab long-term or to switch to another DMT, or in the case of an alternative diagnosis the drug can be stopped.
At Barts-MS we want to promote the #BrainAttack strategy and to potentially do a trial. Please note that if you adopt the #BrainAttack paradigm you need to commit to at least 6 months, and potentially 12 months, of natalizumab treatment, to prevent patients from developing anti-natalizumab or anti-drug antibodies. We rely on the continued administration of natalizumab to trigger high-zone tolerance and to switch off NAB development. We learnt about this when natalizumab was initially pulled from the market in the US after the initial PML scare. Those patients have 1, 2, 3 or 4 infusions were much more likely to become persistently NAB-positive and if this occurs they can never be treated with natalizumab again.
Please note that another issue with these two MSers is that they were both foreigners who grew up outside the UK and simply did not know how to navigate the NHS systems. I think everyone who lives in the UK knows how to navigate the NHS and to be more demanding. I am sure if these MSers had been native to the UK they would have found a way to expedite their appointments. This is no excuse. The tragedy for me is that both these MSers have acquired significant disabilities as a result of NHS systems. I now going to explore the possibility of setting-up an urgent DMT assessment clinic to try an avoid this from happening again.
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48 thoughts on “Why is Prof G dissatisfied?”
This sounds like an irrelevant trial. What would be your hypothesis? treating early is better than treating late?Please stop wasting tax payer money. This commercial endeavour should be financed completely by the direct beneficiary, i.e. Biogen.Please stop wasting your time. This irrelevant work can be done by lesser capable people. Real science and real research please (enough with the observational crap).
I also have a hypothesis that starting natalizumab early may alter the biology of MS, i.e. it prevents the maturation of the B-cell and plasma cell response with the CNS and it may actually disrupt the plasma cell niche. I think the #BrainAttack trial has a lot going for it. Biogen are not going to support it; they have too many other irons in the fire at present and then there is the problem of PML.
The evidence is there that we should start treatment early. No need to more time and money proofing this.On the other hand, how many natalizumab add-on trials are you running looking for an complementary agent protecting the brain from accelerated atrophy?
Re. I think everyone who lives in the UK knows how to navigate the NHS and to be more demanding."I'm not so sure about this, this comes with time and experience. Experience of family and friends and their NHS care, if not your own NHS care. There's also wishful thinking, denial, assuming symptoms are something less important and being unaware and unassertive that can hold pwMS back from being demanding. Thank you for all your hard work Prof G.
wow… this is reality… but… another reality is that out in the parochial hospitals it's even worse. I got myself referred to your team after reading the Brain Health info and looking for as close to the ‘gold standard’ in treating, supporting and managing my MS and all its associated symptoms as I can get in the UK. I have well over an hour’s travel (and cover 80 odd miles) thankfully only 3 times a year, but the financial cost, loss of working hours, the energy (and recovery) needed are worth it. I compare the difference between coming down to London and seeing my local neuro as between seeing a local back street garage (who’ll say well I guess we can get you through another MOT, but next year… who knows?) and taking your car to a dealership (who looks at and thinks about the full life time of your motor!) keep fighting the good fight… affecting change from the inside is easier than from banging on the walls outside the system.
"only 3 times a year"Which drug do you take?
You think in miles?
Good article Prof G. But without sounding like Maria Antoinette. WHEN I suspected in had MS before any doctor and my spinal MRI showed suspect lession. I booked a private appointment and test to get into the system and started treatment within 3 weeks. Ok it cost me £5000. Are we really saying this is a huge sum when y9ur faced with something as devastating as MS? I think cast majority of people in Europe can afford this for their health and family sake.
This is a ludicrous position to hold. What are you suggesting? That every time someone pulls a muscle in their leg they book themselves into a Harley Street clinic to have all the tests done to ensure it is not ALS, MS, Parkinson's etc. and only then can they access a health system that is supposed to be free for all and blind to income levels? Yes, your test proved positive, but you are forgetting that many people have issues that have nothing to do with MS but might present (in the eyes of someone with just MS glasses on) as an MS symptom.
Nope that's not what I'm saying. There's a big difference between neurological disease and pulling a muscle. I was 100% sure what I had before the doctors was because not of dumb luck but educating myself of all the possible causes of the symptoms. MS was top of list so I got appointment for 200 with priv Neuro and MRI for 600 and course of ateriods. I was on the list for his appointment in 3months. I chose to spend money to get ahead of the queue. What's your problem with that? NHS is running out of money.
If you don't see the problem with the idea that the only way to ensure you have a quick treatment on the NHS is to go private, then this isn't a debate that would be cleared up on this blog. And, in terms of symptoms, for many there isn't that much of a difference in terms of presenting symptoms between neurological disease and pulling a muscle. Read the anecdotes of many people who have been diagnosed with MS. I'm sorry that you had to get diagnosed this way, but to thinking it is odd that I have a problem with the idea that in order to get rapid treatment you have to go private… well, I think 90% of people who work in the NHS would disagree with you.
Unfortunately its the world we live in. I blame Donald trump. Also private care is also there for reason. And I was suspect ms on nhs hence 3 month wait to see Neuro. I got the confirmation I need privately. Ps I love the NHS and would gladly pay extra taxes to have the service u talk about. Not one that now only exists in our imagination. But thank you for taking the time to respond to my post. Live long and prosper….
Good news is the Cleveland Clinic is opening up in London. Some healthy competition for the NHS? They don't allow their patients to wait for anything.
Just as long as your wallet is big enough.
Private healthcare is not regulated to the level the NHS is. The NHS is highly regulated. What might seem a fancy flash private hospital may not be so high standard in other aspects and watch out for the unnessessary tests, investigations and treatments in private healthcare. It's about profit with private healthcare.
Also if anything goes seriously wrong, it's off to the NHS to sort it out.
If it was hard to follow up on pills, imagine how hard it would be to follow monthly hospital visits. If Biogen has other things to do other than PML, do you have a way -the money- to solve this problem for good? Would you give a stroke patient Tysabri?Anyway, my question is, would you start a patient on Tysabri from the beginning with the 6.3 weeks dosing since it seems to be equally effective and PML-wise safer?
Natalizumab could be given subcutaneously; Biogen have the data on the sc route. It could also be given 6 weekly, but to do that we need more data on its efficacy, the current data is not good enough. We are already using EID in our centre, but not from the beginning; only later on after it has time to work. Regarding stroke there is a trial going on at the moment to look at its efficacy in this indication. So until we had the evidence no.
Surely giving it subcutaneously would increase the likelihood of generating an immune (neutralising antibody) response to natalizumab? Loads of professional antigen presenting cells in the skin (Langerhans cells).
Can I suggest you consider ‘rebranding’ your #BrainAttack treatment paradigm (which I love) into something like #AttackMS? It will get more traction from the community and won't be confused with stroke.
Very good idea. I think #AttackMS is an excellent name for this initiative and gets away from the issue that MS is not only a brain disease.
I agree #AttackMS is the better descriptor of what you are trying to achieve.
ProfG have you got your 'MOJO' back? This is the kind of post that made this blog a daily read for me. I sincerely hope you are back for good.
I never lost my mojo. Blogging takes an enormous amount of time and effort and I wear many hats. I simply cut back on blogging to focus on other things. However, several people approached me at ECTRIMS to ask why I had withdrawn from the blog, but I haven't just freeing up space for others.
Dear Prof G, I am completely in line with you (B-cell maturation etc.) and would even go further: What about alemtuzumab upon the earliest sign of inflammation? Natalizumab ain't having a bad concept, but surely the clinical data is not good enough (what is NEDA on that?). If you nuke the system once with alemtuzumab very early and prevent B-cell from infesting the brain, chances are people would have a completely normal life with the add-on effect for families and society. Why not doing a "Stop MS in its tracks" study instead of a "hit a bit harder study"? I guess your institution will soon be overrun; they say the incidence rate is 0,0016%, but I bet with you that the real incidence rate has increased to at least 0,16%. How can the official numbers be off by at least two orders of magnitude?
The concept about the #AttackMS (formerly #BrainAttack) paradigm is that it allows you to treat MS and to then step back to think and educate the person with the disease to make the correct long-term decision. Alemtuzumab may be our most effective treatment, but it is irreversible and it is not something you can just do. You have to get the person on board with the treatment strategy and this takes time, not to mention the baseline tests that need to be done. The other problem is MS mimics, you don't want to give someone with an MS mimic alemtuzumab.
Hello Prof G,I am a doctor recently registered at the GMC, I will have a job soon in UK and relocate with my wife and children. My wife has MS and she is currently on rebif. She has mild ataxia from the last attack while she was pregnant 5 months ago. I am asking, how fast will she be put on the DMTs? And, will she be prescribed rebif or else?Her last mri during the attack showed black holes but no recent mri.
To enter the NHS for a chronic disease you first need to register with a local GP and ask for a referral to an MS centre. The management of MS is quite variable in the UK, which is why we are holding a national meeting on variance in the provision of MS services in the NHS in early November. So the treatment options offered will depend who your wife sees. Some MSers are stable and do well on Rebif, i.e. NEDA, therefore, a decision to switch treatment depends on whether she has active MS or not.
"I think everyone who lives in the UK knows how to navigate the NHS and to be more demanding. I am sure if these MSers had been native to the UK they would have found a way to expedite their appointments."Completely disagree with this point! At the time I was diagnosed (a decade ago) I had no idea how to expedite an appointment, navigate the NHS system or even that as a patient I had rights to request which hospital and MS team I was seen by regardless of where I lived. It all comes with time and experience. I see many people from the UK posting on social media their frustrations with the NHS and clearly having no idea how to solve the issues they're facing, which says to me there are plenty of people out there who don't know. Plus not everyone has the confidence to be more demanding – that also comes with experience and health education, or ultimately frustration!
I think we need to design and run an online course called 'Navigating the NHS' for newly diagnosed people with MS and their families. If we did would you use it?
I would have done, yes :))
There's a book published along the same lines, something like 'getting the best from the NHS'.I would use the course you mention, but this sounds a bit like parts of the of NHS EPP Expert Patient Programme.
I am still learning the best way so I think it will be invaluable. Must be done from the patient perspective
PLEASE do go ahead and provide the online course, only please allow for the PwMS experience of things being presented as fact when that may not be the case:For the first 6-9 months post diagnosis I was completely ignorant, not just of how my NHS care should proceed, but also how to effectively research online. I was repeatedly told by a neurologist that I should receive Tecfidera and this was put in writing to my GP, where it was stated: 'I would not describe her as having highly active MS, according to NHS England guidelines' Fortunately, I'd been seen by a neurosurgeon via private health cover, who referred me on to a neurologist. Consequently I was diagnosed as a private patient and the neurologist who diagnosed me mentioned, in writing, my receiving Fingolimod. Consequently, I went back online. I now have a file with sections such as: NHS Constitution on Patient Rights and Choice Framework 2015/6.DOH Referral to Treatment: Consultant-led Waiting Times Rules Suite 2015.Definitions: MS – Treatment: NHS Choices and also Clinical Commissioning Policy: DMTs for Patients with MS 2014.I could go on! Sadly, both neurologists presented the escalation approach as the only one to be applied in regards to MS, and if I hadn't the advantage of Fingolimod having been put forward as a DMT option I would have ended up on Tecfidera for sure!My research led to two things: an understanding that I met the NHS definition of highly active MS and (Thank C****t) stumbling across one of your YT vids ProfG on Alemtuzumab.I pushed back at the neuro who wanted me on Tecfidera and was referred to my third neuro in London. I went to my initial appointment armed with everything in writing as to a) my right to have b) my reasons for wanting to have Alemtuzumab.The MRI of my brain in Dec 2017 was NEDA. This is even more significant in view of the fact I was diagnosed a full 12months before receiving any treatment, other than steroids following two relapses within six months of each other.No one should have to go through this kind of experience with the NHS, but I know it's all too common, and others could provide you with examples of far worse experiences. But, until we become truly informed and knowledgeable patients we will always be vulnerable to falling victim to the system! Before referring me on to a London hospital Mr Tecfidera neuro also repeatedly told me that cost was a factor – that my local health authority couldn't afford some expensive DMTs – nuff said!!!!On a positive note: my care is now excellent and I'm 100% confident that this Blog has assisted in that 😊
HiI also disagree with the notion that people residing in the UK know how to get the best out of the NHS. I was diagnosed with PPMS in 2007 – and was told to expect completely unpredictable progression. My stability and motor control had decreased enough to prompt me to get a referral to a neuro in 2016 – again I was told there there was no treatment and to wait for deterioration.I discovered your MS Ireland 2016 'MS Healthy Brain and Time Matters' on youtube aprox 2 months ago and since then this blog. Your approach makes a lot of sense to me.My point is that over the last 2 months I have been trying to work out how to get even get a referral to the Barts-MS team – I am generally proficient with web searching, hold a degree and until very recently a national sales job – however I still cannot even find an answer to how to get to this first 'trivial' step on the path to sensible treatment.The news that I have probably 'used my reserve up' fills me with sadness – apart from my initial MRI I have had no monitoring or discussion of brain shrinkage etc – I have just been left outside the system.Thanks for your efforts – this blog seems like the best resource currently available.
Hit hard and early!This strategy sounds good, please check the EMA switching label. If you switch from Natalizumab to Alemtuzumab you have to wait for – at least – 3months. So, what you prevent (treating Natalizumab immediately), maybe you lost this switch strategy, and the situation is the same (a real chanche to have a chatastrophic relapse).So pw agressive MS need to have so-so lucky!
In JCV seropostive patients who have been on Natalizumab greater than 12 months we switch to alemtuzumab via a fingolimod bridge to derisk carry-over PML.
Dear ProfG!And what is the optimal switch-strategy from fingolimod to alemtuzumab?
In Scotland, sadly MS capital of the world, you cannot easily change MS teams and just opt to go to a neurologist and MS nurse you would prefer, for whatever reason. It requires a fuss and probably a complaint … meaning a lot of stress whether you stay with a team not helping adequately or attempt to find one that would be better. Will there be a review of NHS services for MS patients north of the border taking account of their experiences too? It is badly needed!
This would be important to cover on the course then, how to diplomatically change your neurologist.
Yes, I think the idea of a course, as suggested by Dr G is a great one, as long as it takes account of the differences between England and Scotland, and perhaps Wales and NI too. Crazy as it seems, in the hotbed of MS that is Scotland there is much poorer access to neurologists with MS specialism and this is made even worse by the fact that many live very remotely. London provision is far better in so many ways … the fact you can even physically get to a neurologist is amazing, let alone choose one you whose approach suits. For whatever reason, the escalation approach appears to THE approach in S, regardless of severity on presentation … but perhaps a topic for another blog.
Brilliant post Prof. G. Re: "I think we need to design and run an online course called 'Navigating the NHS' for newly diagnosed people with MS and their families. If we did would you use it?"Hell yes. Bring it on. I'd happily contribute tips and advice as well as taking it. NHS has amazing services for MSer's, but finding them is the trick. 4 years since diagnosis and I'm finally getting the hang of it. Its not just the NHS though – local councils (disabled facilities grants, council tax reductions), benefits (PIP's, etc.) and grants from support organisation are all a minefield. That being said, this blog is the best placed to cover the NHS minefield. For "Annoymous on Sunday Oct 20th @ 12:53" – RE: How to diplomatically change your neerologist?I did this, well, but perhaps not so diplomatically. I was not geting the kind of support I wanted and expected, and was given annual meetings basically checking I was still alive and still getting worse – to paraphraze my then neuro "your disease is progressive, there is no cure, and we can't do anything other than watch it progress, and if you want advce about medicines, as the MS nurses…"). This left me demoralised and feeling that there was no hope – this was not for me. This bozo had given up on my behalf and I was not going to be a passenger on THAT ride. Here's how I did it: 1. Talk to your existing consultant and say why you are not happy with the situation. I did, he did nothing, so I left. I have no regrets other than I should have done this earlier. 2. Talk to other pwMS and ask who they have as a neurologist and enqure abtou what they are doing with their patients. If its just talk, move on. If you want to move, find out who and where you want to move to.3. Talk to your GP and ask for a referral to another neurologist, hopefully specifying someone or a department in a different hospital. They will outline what you can and can't ask for a refferal for – its not straight forwards. Mine was to question the original diagnosis as some of the symptoms I had did not match. Well, they probably did, but its a way in and a way of having a new batch of tests to actually see where you are in terms of disease activity and progression. My GP was open about this process – the new neurologist/hospital are probably already over-stretched, and lets face it, the good neurologusts probably get a lots more referrals than they can posible deal with. A factor to be aware of is that NHS funding is regional so a referral within your region is more likley to be successful. 4. Like other philosopher's, there is NO number 4. 5. Be persistant. Phone the chosen neurologists secretary/pa and politely ask if there is any news on your referral. At least they know that you are keen. OK, so this probably won't do any good whatsoever, but, it sure as heck makes you feel that you are trying your best and doing something positive and re-take control. Doing something is always better than doing nothing when your conndition is degenerative. 6. If your referral does not work, try again somewhere else. My advice is that if your neurologist is not actively looking for ways to treat your disease activity, it is in your best interests to change this by giving them a prod in the right direction, or moving. Bruce (the Philosopher)p.s. who let the first comment onto the blog? This kind of negative dross does not deserve the space, specially as an opening comment trying to nail the coffin of progression shut.
Re 'Bruce the Philosopher's' comments above. This is all very helpful for other people with MS to read.You do not mention what part of the UK you are in though and the situation and resources/expertise are very different if you live in the Outer Hebrides as opposed to Central London – despite the former having many more MSers per capita. The NHS systems are different, the medical culture and access is different and possibly the PwMS are different too in a general way (another topic altogether). So, def a need for an on line, accessible course which is by and for MSers in all parts of the country, with hopefully the fantastic and dedicated team behind this blog coordinating and advising?!
Annonymous@ Sunday, October 21, 2018 10:34 Am:There is a lot of information out there already on NHS referrals – see:https://www.nhs.uk/using-the-nhs/nhs-services/gps/referrals-for-specialist-care/Your GP will be able to provide advice on the process and is the person who makes the referral.
The book I mentioned is called Staying Alive: How to get the best from the NHS, by Dr P. Hammond. Can borrow it from many public libraries.
I live near Phil Hammond (Somerset) and went to a brilliant talk 'playing games with your doctor' at a local pub a couple of years ago. Think he's doing something similar now if anyone's near any of these venues:http://www.drphilhammond.com/blog/events/Very funny speaker and great advice on how to get the best out of the NHS
When I moved to the UK from the US (having an existing diagnosis and being already on DMF – a frontline treatment here), it took me 7 months to see a neurologist (in Scotland). When I moved here I was told that I couldn't get medicine for that 7 months but that "if I were to progress, I could get seen earlier and then they would do something." But given the time delay from damage to clinical outcome, and the fact that this is permanent f**king brain damage, I was not impressed with this answer. Thankfully, after 3 followup calls with my GP, the neurologist prescribed the medicine for me without having been seen. But it was a struggle and if I didn't fight, I'd be like those stories above. Now I just moved to England (Oxford) and the wait here is 4 months, but at least I was provided with enough medicine to last that time.