Will we ever learn? Just need to Read and Assimilate. Is it too much to Ask?

Results of a mycopheylate study in PPMS

Looks like mycophenolate is down the tube as far as progressive MS goes?

I wonder are Neuros doing their upmost to ensure that we don’t deliver treatment options

Fakih R, Matiello M, Chitnis T, Stankiewicz JM. Efficacy and safety of mycophenolate mofetil in progressive multiple sclerosis patients. J Neurol. 2018. doi: 10.1007/s00415-018-9050-1. [Epub ahead of print]

OBJECTIVES: There are increasingly effective therapies for relapsing forms of multiple sclerosis (MS); however, the options for the progressive patient population are limited. The effect of mycophenolate mofetil (MMF), a disease-modifying agent for several autoimmune diseases, in progressive MS has not been explored effectively. We performed a prospective study to assess the safety and efficacy of MMF in progressive MS patients.
METHODS: We identified 64 patients enrolled in the comprehensive longitudinal database at the Partners MS Center, who fulfilled our inclusion criteria. They were exposed to MMF for at least 1 year with recorded clinical outcomes. Efficacy was assessed by comparing the absolute relapse rate (ARR), and the mean Expanded Disability Status Scale (EDSS) and timed 25 foot walk (T25FW) test scores before and after MMF treatment.
RESULTS: At the start of MMF, 78% of patients (n = 50) were in the 4-7.5 EDSS range. There was a slight increase in mean EDSS from 5.49 ± 1.65 (n = 48) 1 year before MMF start to 5.85 ± 1.56 (n = 48) 1 year after (p = 0.020). The mean T25FW score increased 1 year before MMF from 12.3 ± 9.6 s (n = 38) to 15.6 ± 12.3 s (n = 38) 1 year after (p = 0.009). The ARR in the 2 years pre-MMF period was 0.30 ± 0.63, which decreased to a 0.09 ± 0.29 (p = 0.022) 2 years post MMF.
CONCLUSION: MMF did not affect disease progression but did influence relapse rate. We believe that other medication options should be considered before MMF in advanced progressive patients.

We just seem to be a load of Ostriches who stick our heads in the sand and plough-on without learning anything. 

Maybe because we are incapable of reading other people’s work and assimilating what these papers say, we seem to go from one failed progressive study to the next when using immunosuppressive agents.

I don’t think I am that bright, but at least I can read just about (OK I’m dyslexic).

I would be very surprised if we did not get the results presented in this paper, as we have seen them over and over again.

We know that relapses respond to immunosuppressive agents and indeed that was suggested. 

You can see effects of DMT on gadolinium enhancing lesions within 6 months and relapses within a year, but for progression there is no chance.

So, likewise it was found that there was worsening of lower limb function, which is found in people taking alemtuzumab, ocrelizumab and HSCT, etc. etc, etc., etc., ugh!. 

However, a trial of 64 people is too low to make any firm conclusions and a 12 month trial is too short to detect any meaningful change on lower limb function. 

Although this isn’t a trial and there can be further follow-up, no doubt this paper will now be used to show that mycophenolate is of no value to control progressive neurodegeneration.

Maybe that is the case, maybe it isn’t

Maybe it would be if the study was longer and different outcomes (e.g hand function) were used and importantly if a neuroprotective/repair agent was put on top of the immunosuppression. I guess they can come back in 2 years time and give us the answer.

However, without some control arm will we know if a slowing of worsening occurred.

Why do I say this?

Behind the scenes we have been looking for agents to control progression, but the question I pose is, will we learn from the past or plough-on with the same old trial design..regardless.

However it does show that there is benefit to be had in so-called progressive MS as the relapsing elements clearly respond. However we need to be laying treatments within the therapeutic pyramid, probably with an induction therapy/immune-reconstitution therapy on the bottom

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  • Yet another progressive MS study that doesn't differentiate between patients with active inflammatory disease and those without. Seems to me that mixing these two groups makes for a very murky stew.

    We see this with almost every progressive MS study done. Even the studies involving Ocrevus, which I believe were the most comprehensive progressive MS studies done to date, blurred the lines (deliberately, I think) between those patients with active inflammation and those without. How are we to know the true efficacy of any of these drugs on patients without inflammation if study after study makes no effort to separate the two groups?

    My gut tells me that if the Ocrevus studies had been designed to be able to differentiate between subgroups, we might have found that the "noninflammatory" PPMS group showed far less benefit than those with signs of active inflammation. This goes for studies involving HSCT and any other immunosuppressive/immunomodulatory treatment.

    Thus, those of us stuck in the noninflammatory abyss are left chasing false hopes and, ultimately, to bang our heads against the wall in a so far fruitless search for any kind of treatment to help us. Yes, we are problem children, but it is unfair to toy with our emotions…

  • "fruitless search for any kind of treatment to help us"

    "Neurological function remained stable in the majority of patients.
    Progression-free survival was 69% at three years."

    Lymphocyte reconstitution following autologous
    stem cell transplantation for progressive MS

    DOI: 10.1177/


    • Thanks for the reference, but I believe it pertains primarily to patients with secondary progressive disease. Not sure exactly what study you're quoting from, but all of the autologous HSCT studies I've read display far worse results for people with noninflammatory PPMS than those with SPMS, who very likely have some inflammatory component of their disease still intact.

      If you can show me research that shows significant efficacy in noninflammatory PPMS patients I'll happily change my tune. Until then, I will continue banging my head against the wall and lamenting the current state of affairs.


    • Dear WK
      I think the problem on whether things like ocrevus works in non-active disease is the first question you ask. However, the trial seems to be done in such a way that this can never be properly answered, allowing for a broader licence (in the USA) than simply active disease.

      It will await an academic study and a few more years to answer this..frustrating

    • In this population with high baseline EDSS, a significant proportion of patients with
      advanced MS remained stable for as long as 7 years after transplant. Non-inflammatory events may have contributed to
      neurological worsening after treatment. HDIT/AHCT may be more effective in patients with less advanced relapsing/remitting MS

      17 secondary progressive, 8 primary progressive, 1 relapsing/remitting)

      Bone Marrow Transplantation (2012) 47, 946– 951; doi:10.1038/bmt.2011.208

    • Yesterday was my 5 year stem cell Birthday!!! Five years ago I underwent a Hematopoietic Stem Cell Transplant , which is a chemo procedure to reboot my immune system and hopefully put my Primary Progressive Multiple Sclerosis in remission. Well it worked, and I’m still in remission 5 years later. Here’s a short video I did for my 3 year post HSCT. I’m probably a little stronger now, and have more endurance, but basically the same

    • Luis, first let me offer a hearty congratulations on your HSCT success story, and tremendous wishes for continued success moving forward.

      Thanks also for the studies you cited, very informative. I do question some of the methodology involved, especially when assessing patients with higher EDSS scores.

      I don't think the EDSS scale is fine-tuned enough to pick up neurological progression at higher EDSS levels. For instance, in my case neurologic exams may show that I have been "stable" for the past two years or so, while in reality I know that I have progressed significantly in ways that wouldn't be picked up by EDSS standards.

      My right side remains paralyzed and my left retains function, a situation that hasn't changed over the last several years. However, my right side has certainly weakened significantly, but I'm not sure this would show up in EDSS standards, as my mobility situation has not been tremendously affected by this weakening (it sucked three years ago and it still sucks).

      That said, those with lower EDSS scores might certainly show benefit. What's in dire need are large-scale studies of HSCT on patients with progressive ms, both early-stage and more advanced. These studies need to be quite granular, able to distinguish between patients with active inflammatory and non-inflammatory disease, as well as powered enough to identify just which patients would be proper candidates for a treatment that is not without its risks.

      Strictly judging by your video, it would seem that you would fall into the category of a patient well suited for HSCT; younger, still mobile, and otherwise healthy enough to undergo the rigors of the treatment.

      Again, I'm thrilled at your success, and wish you only more of the same…

    • "It will await an academic study and a few more years to answer this..frustrating"

      Mouse Doc..will only confirm the obvious..if people improved word would have spread. A nurse asked youtuber how he got ocrevus and
      he confirms was in phase 3 trial. He has more wisdom than some
      MD Phd overlooking the obvious.

      "hi I was part of the phase 3 trial for(Ocrevus)it seems to have promise yet it's 1 more drug therapy that only really worked for a small amount of people the rest were little to no benefit. Frankly I'm surprised that it passed worth a shot for sufferers of PPMS.."

    • Let's see what happens after STAT2 completes a phase III study, which I doubt would pass the regulators to approve.

      This is because they have not done a dose-response to establish lowest effective dose and the 80mg simvastatin dose is way above the standard statin dose and does cause side effects in some people that a lower dose may not.

      So if this is positive will everyone start using it. It is unlikely to halt progression completely but more likely to change the rate of progression.

  • Loll

    Thats not me

    That is Vicky Taylor

    2 years ago (agust 2016) i show that video to my neurologist and

    he was speechless

    I said what kind of treatment do you have for this woman ?

    He said




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