Saturday, 1 August 2015

Unrelated Blogger Comments-August 2015

       What to say something unrelated to the thread. Here you go

54 comments:

  1. Please explain the purpose of rebaselining, particularly as it applies to the Lemtrada extension study.

    All it appears to do is make the stats look more impressive. But I want to know how effective it was for everyone, from day zero! Why eliminate those who fail & then recalculate on the successful cases or on those who required re treatment?

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    1. Re: "Rebaseling"

      All drugs take time to work. Therefore we need to reset the clock of MS disease activity after the DMT has had sufficient time to work. For most drugs this is ~3 months. For induction therapy there is no point doing the rebaseline scan until it is time to check whether or not they need additional courses. For alemtuzumab this will at the end of year 2. If you do a scan there an there are active lesions (Gd-enhancing) you will go ahead and give a third course. If there are no Gd-enhancing lesions you will then use this scan as the baseline scan for the next annual scan at the end of year 3. At year 3 you not only look for active (Gd-enhancing lesions), but also new T2 lesions (white scars) when compared to the scan at year 2. New Gd-enhancing or T2-lesions are indication to retreat.

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    2. Thanks Prof G,

      That explains it from a retreatment perspective, but not from a success perspective. I don't see any HSCT studies rebaselining (granted it's a one time treatment). A single rebaselining at year 2 would be justified, otherwise where does it stop? It's incredibly misleading from a statistical point of view where readers want to know success rates amongst the starting population.

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    3. If the DMT stops swelling then you get pseudoatrophy rather atrophy due to nerve loss. So if you dont rebaseline your NEDA-4 can fail for the wrong reasons. HSCT is not planned to be repeated and people doing it tend to be highly active.If you look at the ORACLE opticneuritis cladribine data for MRI for the first 3 months there was an increasese in MRI lesions then it more or less flstlines after that.

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    4. MD, even a NEDA-3 statistic would suffice. Yet I have seen none published in the extension study. NEDA-3 needs to be based on the starting population, not on a select cherry-picked subset of that population. It appears that rebaselining is merely a tactic employed by the drug company to make results look better than they are.

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    5. I am not sure that pharma have been re-baselining their studies,.so you are being cynical for the sake of the the argument.

      This is profG saying that that is what should be done. All you have to do it state after x months of an individual treatment you re-scan.....no skullduggery.

      As to NEDA and extension study, it is not hardwired, maybe the NEDA data was not good....maybe some neuros have been retreating too much.

      However, monitoring NEDA is not going to be simple in the future due to the FDA questioning the repeated use of gadolinium.

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    6. 'However, monitoring NEDA is not going to be simple in the future due to the FDA questioning the repeated use of gadolinium.'

      Oh dear god, I missed this. I've had quite a few MRIs over the years, I've just convinced my rather sceptical GP to refer me for a dexa scan to check for avascular necrosis after the all the steroids I've taken, and now this. What fresh hell would the gadolinium bring? Having MS seems to mean having iatrogenic medicine/treatment at its finest:(

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    7. A Lemtrada vs HSCT debate? Man, there's not been one of these on here for ages! I'm fit to burst! :)

      I get what both sides are saying on this - and I think it relates primarily to the Lemtrada studies (rather than any other MS drugs). I fully get rebaselining and why it's important if you're a doc treating a patient. That makes perfect sense. And also why it's important to record this in a trial setting.

      My only thought would be that the way NEDA results are sometimes reported (and compared) in relation to clinical trials can give a (beneficially) distorted view of the efficacy of the treatment to your average MSer.

      For example, if I'm looking at treatment options, and I see on this blog (or elsewhere) that Lemtrada has a NEDA rate of 70% (or whatever it is). To me, that means that 7 out of every 10 patients who went on this treatment did not show any signs of disease activity against a pre-treatment baseline. Or, in other words, on the strong balance of probability, I'm not going to have any progression/lesions/relapses if I go down this route! Yay!

      But, sadly that's not what it means at all. Because, as the actual trial data shows after CARE MS-1, only 40% were NEDA at 2 years. Which ruins my stats party, cos now on the balance of probability, I AM going to have progression/lesions/relapses if I go down this route (not yay!), though admittedly if I keep on being retreated the outlook of avoiding further relapses beyond that may become progressively brighter and eventually reach 70% - but this is NEDA against (potentially) post-treatment additional relapses/lesions/progression.

      That's why it can be a bit misleading if your goal (as an MSer) is to achieve NEDA based on your EDSS/lesion count today - cos a substantial proportion of these NEDA people in the trial data actually have accrued additional lesions/EDSS progression before they reached a point after 3, 4, 5 years of retreatment where they hit a period of stabilisation.

      I don't think it's skullduggery particularly, but I do think that it's not always particularly well explained to MSers. Certainly as more therapies with potential to induce NEDA arrive on the market, there will need to be some care taken as to how efficacy is compared on a like-for-like basis.

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  2. I've asked this a few times in the past but haven't received a reply :(

    Does anyone else have pressure/tightness in the temples on a daily basis? Is this also MS related?

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  3. Anon 10:08am: may I suggest a general Facebook forum or the like? They are comprised solely of patients & you are more likely to find others experiencing similar symptoms there.

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    1. Oh yes, apparently not MS-related, well, that is main reason it took so long to get an official diagnosis, as had this from age 15.. However, I checked every conceivable thing from eye strain to migraine first and it wasn't any of these.
      Can't obviously say what you experience is the same thing. I now have TN - a world of difference from the temple tightness, which I still have (idiopathic facial pain), mainly on relapse for some 34 years now.

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    2. Thanks Anon 11:43 for your response - is there anything that you find helps with this tightness or has it just gotten worse without much relief? Or maybe you got used to it a bit?

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    3. Hi again, it has got better over the last ten years and now I mainly have it on relapse, so the best thing is not to have relapses:).

      I've tried mindfulness with a clinical psychologist -sort of works but I can't really judged because of the TN pain, which I have a lot more often (and I'm not really adept at being mindful when all I want to do is take a hammer to my face:)).

      Warm autogenic relaxation helps somewhat (the psychologist's suggestion, you can find lots on YouTube, google the name plus keyword "pain").

      I've also taken gaberpentin but the side effects far outweighed the benefits for me, possibly the carbemezepine for the TN, but again I can't really judge as the temple tightness is now more transient.

      Have you checked you eye sight and for migraines to be sure it is not this? Otherwise, perhaps the warm autogenic relaxation is a good place to start as it's unlikely to do any harm and might help (hope so).

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  4. Anon 11:24 yes of course - thank you very much for your suggestion :) have a great day!

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  5. What are the effects of Monosodium Glutamate (MSG) on an MSers brain? Should we avoid Chinese food?

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    1. I don't think its good for anyone regardless of having MS.

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    2. I went for a really enjoyable lunch with work colleagues at a lovely Chinese restaurant. I didn't drink alcohol. As I stood up at the end of the meal I had an almighty migraine, ended up in the firm's sick bay and a colleague had to drive me home. I don't think it affected my MS, but it sure gave me a headache. I still eat Chinese at places that don't use MSG.

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    3. MSG can trigger headaches, so can chocolate, caffeine, chilly - life's too short...

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  6. Another interesting one
    http://news.virginia.edu/content/scientists-id-cause-movement-balance-problems-multiple-sclerosis

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    1. http://www.cell.com/immunity/abstract/S1074-7613(15)00120-X
      Published in April.

      Missense mutations in the nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing family of gene 12 (Nlrp12) are associated with periodic fever syndromes and atopic dermatitis in humans. Here, we have demonstrated a crucial role for NLRP12 in negatively regulating pathogenic T cell responses. Nlrp12−/− mice responded to antigen immunization with hyperinflammatory T cell responses. Furthermore, transfer of CD4+CD45RBhi Nlrp12−/− T cells into immunodeficient mice led to more severe colitis and atopic dermatitis. NLRP12 deficiency did not, however, cause exacerbated ascending paralysis during experimental autoimmune encephalomyelitis (EAE); instead, Nlrp12−/− mice developed atypical neuroinflammatory symptoms that were characterized by ataxia and loss of balance. Enhanced T-cell-mediated interleukin-4 (IL-4) production promotes the development of atypical EAE disease in Nlrp12−/− mice. These results define an unexpected role for NLRP12 as an intrinsic negative regulator of T-cell-mediated immunity and identify altered NF-κB regulation and IL-4 production as key mediators of NLRP12-associated disease.

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  7. Please excuse my ignorance. How is PPMS diagnosed? What is the criteria?

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    1. As a person with PPMS, I found this booklet extremely helpful. (It was the first information booklet on MS that brought clarity to me: All the stuff I'd read about MS relapses was alien and didn't sound anything like what I had.)
      http://www.mstrust.org.uk/downloads/primary-progressive-multiple-sclerosis.pdf

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    2. Just read this document, thank you. The author states that the Macdonald criteria was revised by another neurologist called Ian Macdonald, is this right? I thought it was the same person. They used to call him Mr MS UK. Any neuros out there have the answer?

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    3. Originally they had the poser criteria and then we got the macdonald criteria. This was named after the NewZealander Ian MacDonald who was prof at queen square in london. There have bèen other criteria such as the Barkhof criteria but the MacDonald criteria is the main one used at the moment. This has been revised since it was first used and mixes imaging withvthe clinical profile.

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  8. Article by Aussie / NZ neuros on new treatment era. Worth reading.

    http://www.msra.org.au/australasian-neurologists-review-new-era-ms-treatment

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  9. Mediterranean Diet May Preserve Brain Structural Connectivity (news 7 August )

    http://www.medscape.com/viewarticle/849205

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  10. Having become allergic to all dairy products and beef as an adult - after my PPMS symptoms began to become apparent - and now that I am also beginning to suspect egg whites of triggering migraines, I am wondering if anyone knows of any research into the interrelationship between allergies and MS? I wonder whether certain protein allergies are a common by-product of the disease process. Or has one absolutely nothing to do with the other...

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    1. I have Cealics Disease, which according to my neurologist often occurs with MS. Before I was diagnosed it was sometimes very difficult to distinguish an MS relapse from eating gluten as the neurological symptoms are so similar. I have allergies to many things from childhood (thankfully not dairy) and often wondered if this was related to some/any extent to the MS.

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  11. Activity of entire central nervous system captured on film for first time
    Wow, just wow!

    http://www.theguardian.com/science/2015/aug/11/activity-of-entire-central-nervous-system-captured-on-film-for-first-time

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  12. Taking DMDs in SPMS to slow down future worsening of symptoms - is this something that is/will be worked on, do you know? Ref ProfG's opinion that SPMS trials have not run for long enough, in the past.

    Have tried posting this a few times before, without success, sorry to keep repeating the same question. It's not always easy to distinguish soups/bread/pasta etc in the verification dialogue!

    Thanks, Bouncy

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    1. The problem of having long triaĺs is the cost. I think the ascend trial is being extended, so the answer is maybe. I think if we had a cheap induction therapy this could beca backdrop to layer protective and repair agents.

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    2. Thanks for your reply, MD.

      Is it possible/feasible to go back to the original people onthe trial and see how they are doing now, or is htat completely off the wall?

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    3. I am sure it is but whether they decide to do this is another matter.

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  13. When are we going to here about the inspire trial? Or more on the viral hypothesis? Everything appears to have gone very quiet ...

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  14. I'm hearing about more and more people accessing HSCT on the NHS (outside a trial). Have I missed something? and is there any news re ZEUS plans?

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  15. I spotted Prof G in in the MS Trust's Open Door Mag - great to see, early, aggressive treatment is gaining momentum.

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  16. Team G, am I the only MSer to make a comment and it doesn't get posted? It's been a few days since I left the comment and no can see. It has happened before.
    The comment does not state peoples names or company names, it's not about marketing or advertising and I am not asking for personal advice.
    I spent maybe 10 mins writing the comment.

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    1. When was the comment posted and what was it about?
      I have not deleted any comments besides the usual spell caster, Herpes spam. MS Unites had got themselves straight to spam and these have been launched.

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  17. Posted Thursday. The post was about Employment and MS. My comment discussed how my working life has changed since being diagnosed with MS. I was suffering from stress for years during my job when I was well. Then I had major life changes, a series of unfortunate events and my first MS symptom showed.

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    1. There is nothing in spam for 20th and of the posted comments I can't see anything that has the same subject matter. So sorry I don't know where the comment went

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    2. Anon - I got caught out a few time when I first posted comments as sometime when you have the green tick showing after proving that your are not a robot you then need to scroll down a bit further to see the Publish button. If you do not click on the Publish button your comment will not get uploaded for clearance by the blog moderators. Once you have clicked on Publish you should see a note about "Your comment will be visible after approval". If you don't see this, then I suspect that your comment has not uploaded.
      Glitches happen occasionally, and I now take the precaution of highlighting my entire comment and copying the text (Hint: Ctrl A + Ctrl C) before proving my non-robot status. That way if the cyber gremlins have a go at me I can simply re-enter my comment.

      Just some thoughts that might help you.

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    3. Thanks Anon for the tips. Good idea to copy the text, I will try to remember that. Though I do remember seeing the pizza pictures for my non robot status.

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  18. There is a trial still recruiting people with secondary progressive MS in Australia and New Zealand

    https://clinicaltrials.gov/ct2/show/NCT02228213

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  19. BBC news article today about about low vitamin D genes link to MS.
    People genetically prone to low vitamin-D levels are at increased risk of multiple sclerosis, a large study suggests.
    http://www.bbc.co.uk/news/health-34055529
    Good to see it in the news raising awareness of MS.

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  20. Maybe you've already commented on it but I saw that in Medical News today NIH have developed an Epstein Barr virus vaccine that produces potent neutralising antibodies in mice and other animals They use nanoparticles and target gp350 whcih helps EBV attach to B cells? Hope it's the beginning of the end for future MS

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  21. Team G my local wellbeing centre is running free talks on subjects such as coping with stress and anxiety, boosting your immune system. The stress and anxiety talk is a great idea.
    Do MSers need to avoid boosting their immune system?

    Many thanks

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  22. Curious, you have recently posted an blog post about patients being unable to make treatment decisions and gave a specific alemtuzumab vs nataluzmab example. Whilst I agree it can be very difficult for patients to make those decisions, I find it amazing that doctors don't tell the full truth regarding drug trials and 'spin' facts to support their own arguments, which I think is disgraceful.

    Regarding Alemtuzumab, (which I am currently taking) if you ask many neuros and read this site and others, you hear of its 70% efficacy, but that is NOT fully supported by the trial data.

    Neither of the two major trails fully support this, in fact CARE MS trial, after 2 years only 40% of people reported no relapses or progression, this does change after you re-baseline but it means in simple terms. If you are a 1 on a EDSS Scale, there is a 60% chance that you will have another relapse and accrue further disability whilst the medicine is 'working.' Then if we need to re-treat youwe re-baseline our results and then you get close to 70%. If you tell patients that, and then give the same HONEST stats about Nataluzmab (which I don't have to hand) is it not easier for the patient to make a decision?

    Is it not also time you took down 'wishful thinking' media saying 'some drugs that almost offer a cure I think - one of the drugs I've been working on is alemtuzumab....' FACULTI video with Prof G on YouTube. I think it's irresponsible to say things like that when you have NO evidenced of the RRMS SPMS effectiveness of alemtuzumab, and we know that alem does not stop progressive disease

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    1. in CARE trials the efficacy in relapse rate was not as good as phase ii where it was 80% better than beta interferons in the CARE trials are against beta interferons they should be 30% active so that needs to be factored in as it is not against placebo.

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