Saturday, 13 February 2016

ClinicSpeak: are you avoiding the Big Issue?

Is it time to stare-down the beast of SPMS? #ClinicSpeak #MSBlog #MSResearch

"Time for a rant; apologies upfront if the following post upsets you."

"We have had so many problems recruiting for the PROXIMUS trial that I beginning to doubt the wisdom of doing the trial. The idea is simple enough; try and add-on neuroprotective drug in early secondary progressive MS (SPMS) to see if it can stop, or at slow down, the neuroaxonal loss that underlies progressive phase of the disease. The primary outcome is neurofilament levels in spinal fluid. As you know neurofilaments are released when axons degenerate and raised levels predict a poor outcome. What we are testing is whether or not a putative neuroprotective drug can reduce neurofilament levels."

"What I have now discovered that many of my fellow healthcare professionals are reluctant to to discuss the PROXIMUS trial with their patients as it means that have to mention the dreaded topic of secondary progressive MS. Why have the conversation if you don't need to? A lot of people with MS who are on DMTs know they are gradually getting worse; they notice their cognition, walking, balance, sphincter function, etc., deteriorating, month-by-month or year-by-year. Why would they want to deny it? Is SPMS such a taboo?"

"I have argued many times before the pathological processes that drive progressive disease are present in the majority of pwMS from the outset. This is why we are starting to measure brain volume changes and CSF neurofilament levels in routine clinical practice; we need objective information to tell people that their MS is progressing despite them not being aware of it. There is no point ignoring the elephant in the room. If want to change the natural history of the progressive phase of this disease then we are going to have to get our heads around diagnosing progressive disease as early as possible. There is no point waiting for the shredder to take you to EDSS 6.0 before you accept you have SPMS. It is better to face-up to the possibility early on so that we can try and do something about it."

"The natalizumab in SPMS trial was negative, simply because the majority of pwMS went into this study with an EDSS of 6.0 (walking stick) or more. The ocrelizumab in PPMS trial was positive because the majority went into the trial with an EDSS of 5.0 or less. The message from these two studies is clear; the earlier you target progressive MS the greater the chances of us doing something about it. So if you are on a DMT and have not had a relapse in the last 6 months and you feel as if you may be getting worse you may be interested in participating in the PROXIMUS trial. How are we going to improve the lot for pwSPMS if don't get the community to wake-up to the fact that progressive MS is something to be discussed and tackled head-on; it is not something to be ignored and denied until it is too late to do something about it."


"For those of  you who have SPMS or PPMS and have already lost leg function, don't get despondent. We are in the process of designing treatment strategies to protect your upper limbs and bulbar function (speech and swallowing). We don't think we should give-up on you simply because MS has affected your walking. We would also encourage Pharma and the Regulators to think again about this; why should we write-off arm function simply because leg function has been lost? When someone loses the ability to walk their arms and hands become their legs. This is why it infuriates me when I seen non-evidence based DMT stopping criteria based on EDDS; i.e. if you get to EDSS 7.0 you have to stop your DMT. What about arm function, what about bulbar function? What people don't realise is that although the natalizumab in SPMS trial was negative it had a major impact on preserving arm function. Surely we should be focusing on that positive? An holistic approach to MS requires us to remove the EDSS blinkers and focus on what is important to pwMS and that is a moving target depending on the stage of the disease (no disability to severe disability)."

CoI: multiple and I am the chief investigator on the PROXIMUS trial

28 comments:

  1. What is the difference between Proximus and MS SMART as they seem to be nearing their target if they are closing in April?

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    1. Proximus - you have to be on disease-modifying treatment and you receive a neuroprotectant as an additional treatment.
      MS-SMART - takes those not on treatment and tests three neuroprotectants.

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  2. Part of the problem is that no clinician will put their head on the block and say what the final consequences will be. You are suggesting that there is an inevitable pathway that needs to be recognised. The unpredictable part is the rate of progress

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    1. The rate of progress is the same once you have hit progression - I refer to the natural history studies by the late Confavreux and Ebers. But why publicise what is essentially bad news, we should be looking at ways of solving this.

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    2. can you link those studies? i'm not sure i understand the comment that the rate of progress is the same once you have hit progression

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    3. Confavreux - graph on p270 (http://www.direct-ms.org/pdf/EpidemiologyMS/Confavreux%20MS%20Risk%20Facotrs%20CON%2007pdf.pdf).

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    4. Thanks! I really enjoyed the paper and understood all of it except for the graph on page 270 lol... I'm sure I'm not reading the two graphs correctly, but they look confusing. The time of progress for PPMS to DSS 6 should be the same in both graph - (a) since the onset of MS and (b) since onset of progressive phase, but they don't seem to match?

      Given that they are median figures it seems there is still room for individual variability. Why advertise bad news? Imagine a cancer patient having 50:50% chance of dying in the next 8 years and an oncologist not telling the patient this as it is essentially advertising bad news lol.

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  3. How many have you recruited so far and how many more to go?

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    1. PROXIMUS or SMART?

      Lots if you are eligible please consider for both,

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  4. I guess we're all doomed, then. One day this blog states that MS is now curable, the next we hear that even whilst on DMTs we're headed for SPMS.

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  5. Re:"There is no point waiting for the shredder to take you to EDSS 6.0 before you accept you have SPMS. It is better to face-up to the possibility early on so that we can try and do something about it." Aye there's the rub........what can we do about it? Once patients are heading down that slippery slope of disability clinicians just seem to throw their hands in the air and state you are now in the progressive phase and the DMTs are of little use. I also get the feeling that Pharma seems content on peddling the current crop of drugs. They are generating a healthy profit seeing that patients are on them for 10-15 years before progression sets in. They can test current MS drugs for efficacy in SPMS but I think deep down they know they are of little use. At this stage of the game progression should be the main focus in MS research. Let's hope (using that word again) that something breaks on the progressive MS front. Good luck with Proximus and SMART.

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  6. Mad world when those who get a grim disease are blamed for a lack of progress in finding effective treatments for the progressive forms of the disease. Surely the blame lies with the researchers who can't work out what this disease is about. We have more powerful MRIs, unbelievable computer processing power, and the internet to share ideas / findings at the click of a button. Where is the progress? We are just taking punts on back of fag paper ideas and drugs which can never make it to market. CUPID trial, Charcot 1, Tysabri for SPMS...

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    1. Given the human race has been around for over 125,000 years, we have done rather well since the development of the scientific method. And in the last 50 years a great deal has been learnt. That said some problems are hard and the existence of hardware is not what you need, what is needed is new ideas or just one piece of information that helps you explain everything. Every idea is built on top of the last idea, there are no short cuts. Researchers are not magical, they cannot magic the jigsaw to completion.

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    2. AnonymousSaturday, February 13, 2016 10:39:00 pm I do understand the frustration, but the blog entry specifically names the "fellow healthcare professionals" as being responsible (because they are the gatekeepers of information).

      '"What I have now discovered that many of my fellow healthcare professionals are reluctant to to discuss the PROXIMUS trial with their patients as it means that have to mention the dreaded topic of secondary progressive MS. Why have the conversation if you don't need to? A lot of people with MS who are on DMTs know they are gradually getting worse; they notice their cognition, walking, balance, sphincter function, etc., deteriorating, month-by-month or year-by-year. Why would they want to deny it? Is SPMS such a taboo?"

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  7. I would volunteer for Proximus if I could but don't fit the criteria :-( I'm sure there are many more like me. Very pleased that you are trying to help with upper limb and cognitive issues, and yes it is a travesty that so much rests on EDSS which is so influenced by a person's ability to walk. It doesn't show a real understanding of people's lived experience.

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    1. Yes but i think there are also alot of eligible people that are not being informed of the possibility or are being put off the idea because it is not explained properely

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  8. I have gone through hell and back with 5 neuros over the last 12 months, of which 2 were good and 3 scare mongerers.

    I honestly didn't think I could reach a new low of despair in this misery called the MS industry, but this one has made me want to bang my head against a very hard surface... What is wrong with your colleagues? I've been searching for an answer since my partner's diagnosis (the MS has been a charm to deal with in comparison with the neuros)... but do these people live on planet Mars with cotton wool inside their ears going "lalallalala"?

    "What I have now discovered that many of my fellow healthcare professionals are reluctant to to discuss the PROXIMUS trial with their patients as it means that have to mention the dreaded topic of secondary progressive MS. Why have the conversation if you don't need to? A lot of people with MS who are on DMTs know they are gradually getting worse; they notice their cognition, walking, balance, sphincter function, etc., deteriorating, month-by-month or year-by-year. Why would they want to deny it? Is SPMS such a taboo?"

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  9. i'm starting to think that the majority of neuros out there believe ms is about them, not their patients....

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  10. My partner has had breast cancer and MS, in that order. She regularly annoys her neuro by telling the neuro that her cancer medical experience was far more favourable and easier to deal with than the MS.

    Recently, a little boy in Australia died from cancer. This was his (world renowned) oncologist's eulogy at the boy's funeral.... I think it's relevant.

    “When I was asked to speak at Rafael’s funeral, my first inclination was to say no. But I felt that we had an unfinished journey together and I agreed to speak to express my thanks to involve me in your wonderful family.

    My last eulogy was not that long ago for my 93 year old father. I said at the time that my father had a long life lived well. I can say that Rafael had a short life but lived brilliantly. You might think that death represents the ultimate proof of the impotence of medicine in the face of cancer. Some doctors avoid the funerals of their patients, seeing it as a manifestation of personal failure.

    I am afraid, I can’t see it that way at all. For me, medicine isn’t about preventing death, which is inevitable. It is about prolonging and enhancing the life, not only of the patient, but the family who goes with them. A patient of mine described the prospect of dying of cancer being like standing on the edge of the Grand Canyon and looking down, realising there is only one final destination, but two ways of getting there: over the edge or by the donkey trail. He reflected with gratitude before he died that despite the occasional bumpy and uncomfortable road, the later was much more preferable, as long as one takes the time to admire the view on the way down. Raphael also took the scenic route and what a great ride he had!”

    Recently a man with MS from Australia decided to end his life by refusing further treatment. The man gave so much to the MS society and the MS society refused to discuss the issue.

    So much gutlessness around people with MS. Is it any wonder people with MS are angry?

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  11. VERY VERY WELL WRITTEN Prof. G. Question is what can be done regarding this in the patient (preferably global) population??? Tell us what we need to do in order to start bringing this issue to LIGHT. SPMS scares the crap out of every RRMSer including myself. HOW do we have this discussion globally? What can we do to foster it happening?

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  12. Perhaps it should have been promoted more widely - as an MS Nurse, I have been kept abreast of MS SMart from the outset - not so with PROXIMUS

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    1. You're right on the ball with this, getting the word through is a failing of many investigator led studies. Normally, only the patients under the host site and related centres are aware.

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  13. Why are you only recruiting people who are EDSS 6 or lower for this trial?

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    1. If you read the article above you will understand that its easier to measure a neuroprotective effect if the EDSS is lower. This was shown in the cannabis CUPID trial. Thats not to say we're giving up on those with EDSS of 6 and above, far from it but we need studies like PROXIMUS to show what are effective neuroprotectants before we can proceed.

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    2. Am I Correct that one cannot participate in the PROXIMUS trial unless in the UK? Any chance of trial in US?

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  14. It's strange, the different perspectives on this disease. I have had very limited experience of flares, of something of what "RRMS" must be like - random temporary symptoms that then resolved. That, for me, was _much_ more frightening than my plodding, slow, most of the time not doing a lot (touch wood) "PPMS".

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