How can RRMSers recognise it is time to switch DMT? Would this be after how many relapses and how many new lesions on MRI? I know we are aiming for NEDA but is that really realistic on many of the DMT's?
It depends on which DMT you are taking. Have the discussion with the neuro
1. New avenue for MS cause and future treatments?The study, “Structural Transition in Myelin Membrane as Initiator of Multiple Sclerosis,” was published in the Journal of the American Chemical Society (JACS)2. Why is there no discussion by the Bart's team for the ECTRIMS research presented re: alpha lipoic acid in treatment of progressive MS? That ALA showed 66% reduction in loss of brain volume on MRI compared to placebo (p < 0.004) should be big news, shouldn't it?
Simple I was not in the session because I was too busy doing other things.I have now watched the video and posted, it will be big news if this study is repeated in larger numbers with a clinical effect as brain volume has many issues. Too often we have a series of small neutriceutical trials going nowhere. I suspect these sort of reports make people take the neutriceutical, but the lacks the evidence base needed.
Reading about the trial of the HIV treatment which launches a two-stage “kick and kill” attack on the virus.The new therapy is unique in that it tracks down and destroy HIV in every part of the body —including in the dormant cells that evade current treatments. (The Independent) Does this mean anything Antiretroviral therapy trial for MS?
Interestingly this was published today: the first proof of a direct association between coronavirus and neurological diseasehttps://www.eurekalert.org/pub_releases/2016-10/indl-fpo100316.php
Not to pee on the bonfire - but I was expecting something from ECTRIMS about raltegravir.... and read that it had failed in one trial.“Raltegravir had no significant effect on MS disease activity as measured by either the number or rate of development Gd-enhancing lesions during the treatment phase compared with the baseline phase.”What does Prof G and others say of this....? http://www.hcplive.com/conference-coverage/ectrims-2016/hiv-drug-does-not-impact-ms-disease-activity#sthash.anIo9TuG.dpuf Was
The study was presented at ECTRIMS and it failed.Is it worth more page time as the headline result was given...when the study is published then maybe ProfG's may present it.
Coronavirus that causes respiratory infections, causing a similar encephalopathy MS... http://www.nejm.org/doi/full/10.1056/NEJMc1509458?rss=searchAndBrowse#t=article
Pretty surprising to find DMT to suppress cancerDimethyl fumarate restores apoptosis sensitivity and inhibits tumor growth and metastasis in CTCL by targeting NF-κB.https://www.ncbi.nlm.nih.gov/pubmed/27268084
https://elifesciences.org/content/5/e18246Some Mouse Doctors in the US are doing good stuff testing a drug for remyelination benefits. I think there is a trial in humans of this drug, but not sure.
Thanks well have a look, yes there has been a trial
http://www.cell.com/neuron/abstract/S0896-6273(16)30585-2?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0896627316305852%3Fshowall%3DtrueThe Calcium Channel Subunit Alpha2delta2 Suppresses Axon Regeneration in the Adult CNS>Alpha2delta2 pharmacological blockade through Pregabalin (PGB) administration enhanced axon regeneration in adult mice after spinal cord injury (SCI). As PGB is already an established treatment for a wide range of neurological disorders, our findings suggest that targeting Alpha2delta2 may be a novel treatment strategy to promote structural plasticity and regeneration following CNS trauma.Well Lyrica is safe and readily available medication.
whilst recently seeing the 6 year data for Alemtuzumab from in the CARE trials, I realised that the results that are published are almost a fabrication. They allow re-baslining into their results. Why do you and the trial owners think this is a good way to publish this data? As to me it looks like statistical manipulation to make a drug seem a lot more effective than it actually is.If I have 2 rounds of treatment, and then have no relapses for 6 years, that is the data that is relevant to the majority of MS'ers.However If I have 2 rounds of treatment, then no relapses for an additional 2 years, then have a relapse, another round of treatment and then 1 year relapse free do you think it is right that my results are included as being NEDA in years 1, 2, 3, 4 & 6 but not in year 5? That seems like a con to me, it also seems like a con when you say that HSCT and alemtuzumab have similar efficacy profiles, when in HSCT you rarely if at all re-treat and in alemtuzumab you have a 'if at first you don't succeed try again' approach, If you adopted the same approach with HSCT you think you will see even better results?Can you explain the logic in this? And why you don't interpret the data more honestly/clearly to give patients the maximum information around treatment?
Is this true? I thought Lemtrada had over a 50% chance of NEDA and was potentially a cure. What does rebaslining do to the results? I'm now confused...
I cant explain logic...sounds like....massaging data:-(
As alemtuzumab is an induction therapy you need to re-baseline prior to being able to give the third course. Therefore, NEDA rates in year 1 & 2 are not that important. When you look at cumulative NEDA rates over 4 years they are ~50%. It is important to note that if you break through on an induction therapy it is an indication to retreat and not necessarily and indication that you are a non-responder. I say not necessarily because there comes a point in time when, probably after 4 or 5 courses, that you will need to call it a day and say you haven't responded to the therapy. I will post on this issue when I get time; we presented the 4-year data at the AAN earlier this year.
Dr G, I have no problem with re-baslinging after you have finish the initial 2 courses, as during that year you are still within treatment cycles.The problem is that if after two rounds of treatment, you go NEDA for 2 years, then relapse, then re-treat, then go NEDA in year 6, Including that patient as NEDA in year six stats is just wrong, and very misleading. (Your colleagues imply that they understand or maybe even agree with me)As an MS'er who has finished my 2nd round of Alemtuzumab, if I relapse after two NEDA years, and need re treatment. I should be rebaslined to the beginning after re-treatment. It makes so much more sense and it so much more logical to say. (Using made up stats here and 100 patients as an example)2 Year Treatment ONLY50 patients has 2 courses of treatment and remainder NEDA (no additional treatment for 5 years)1 Additional Re-Treatment required (course 3)50 patients required 3 round of treatment, (10 after 1 year NEDA, 20 after 2 years NEDA, 20 after 3 years NEDA)Of the 10 1 Year NEDA and Re-treated with a 3rd course, 8 are NEDA for 3 yearsOf the 20 2 years NEDA and Re-treated with a 3rd course 15 are NEDA for 2 yearsOf the 20 3 year NEDA and Re-Treated with a 3rd course 10 are NEDA for 1 year2 Additional Re-Treatment required (course 4)Etc etc etc (details of the 17 listed as above)It's more complicated to write out (but much easier to show is a graph) and much more honest. It baffles me that we allow false statistics to be reported, (as as someone who works with numbers)I know how to massage figures, but as doctors and researchers I am surprised that You don't unpick it for your patients. (Not surprised Pharma act this way, as they are shareholder driven!)
You are describing a Kaplan-Meier curve, i.e. time to re-treatment. Cumulative NEDA rates on alemtuzumab are only about 50% at 4 years; the latter takes into account re-treatment. Because of this I have always said that an induction therapy such as alemtuzumab will never beat a high-efficacy maintenance therapy if the outcome is NEDA. With maintenance therapies not-NEDA would need to be the outcome for the survival curve and that is less likely, than NEDA, once you are rebase-lined. For example with ocrelizumab it is 80% at 2-years. Most of us who understand the way these treatments work have no issue with these differences. What you are trying to do is compare alemtuzumab to maintenance therapies using NEDA as the outcome; the answer is alemtuzumab will be inferior. If you flipped the coin as made the comparison long-term remission, i.e. time to re-treatment after stopping the treatment say at year 2 then alemtuzmab would be superior.
I appreciate your response, but wonder if you/most neurologists explain that to patients when they are making treatment decisions. Another question is around alwmtuzumab vs HSCT. You don't re-treat in HSCT (or very rarely) so it's not an induction therapy using that logic. Yet you compare the results to HSCT which is induction and state the results are very similar. Using the Kaplan-Meier result logic (as to compare these 2 treatments any other way would seem to be unfair) Do you stand by their similar efficacies that you have said before or accept in direct comparison HSCT is significantly more effective?Also - do you still believe that alemtuzumab has potential as a cure? (Or has it cured some patients already) or so you believe long term remission (then re-treat) is more accurate?
HSCT fulfills the working definition of an induction therapy. I have never said that HSCT and Alemtuzumab have similar efficacies. All I have stated is that they are both very high efficacy therapies and the only way we will be able to assess which is more effective is in a head-2-head study. There is a lot of discussion on this latter on this blog under the ZEUS trial. We the UK MS community put two grants into the NIHR on HSCT and got them rejected. One grant was to compare non-myeloablative HSCT to Alemtuzumab/Natalizumab and/or other emerging high-effiacy therapies (e.g. ocrelizumab). The second grant was to compare non-myeloablative to myeloablative HSCT. A lot of the questions that need answering re HSCT are about risks, mainly safety, and cost-effectiveness. If the procedure proves safe and cost-effective then a lot of units will be offering it under the NHS.
Re cure. I have put forward a working definition of this on the bog before. We haven't got there yet. It is 20 year experiment. We need to be patient.
Sorry ProfG, you have said that HSCT and Alemtuzumab have similar efficacy, see the below post published by you. I am sure I have read it more than once in this blog.http://multiple-sclerosis-research.blogspot.com/2015/01/clinicspeak-are-we-being-too.html'It is clear from reading comments on several recent posts, including yesterday's post, that a large number of you would prefer the option of non-myeloablative, or ablative, hematopoietic stem transplantation (HSCT) to alemtuzumab treatment. Is that correct? HSCT looks to have the same or higher efficacy than alemtuzumab treatment and seems to come with a lower risk of secondary autoimmunity.'What i fail to understand is that if they are already treating some patients for HSCT at or in conjunction with Imperial, (Dr Richard Nicholas et al) you have your test data right there, I am sure they have patients taking alemtuzumab in those hospitals as well! Surely a conversation within the neurology community could make that happen.Re: Cure. Do you know/treat any Alemtuzumab patients who are post 14/15 years since last treatment who have had no relapses/or progression in disability/not converted to SPMS. Do you have a Kaplan-Meier curve of the original test subjects from the early 2000's. (not a statisticial manuplication like CARE MS trials publishes the data) I have read that the average RRMS'er converts to SPMS at around 10 years (on this blog) I have also seen posted that roughly 30% of MS'ers have the inaccurately called benign MS and don't show any progression/relapses post initial lapse for 15 years. Are stats like the above, and many more taken into consideration when you are talking about a cure?
You are misquoting me. In the post you are referring to I state."HSCT looks to have the same or higher efficacy than alemtuzumab treatment and seems to come with a lower risk of secondary autoimmunity."I have always supported the need for a head-2-head study. The ZEUS trial, which we are trying to get funded, is exactly this. We simply can't make comparisons based on the current published data. There are too many biases etc. that make this impossible. In addition, many of the HSCT induction protocols include alemtuzumab as part of the treatment regimen. I don't know if patients who are NEDA 15 years post-HSCT, or alemtuzumab, are cured. I have proposed to a deep phenotyping study to address this: http://multiple-sclerosis-research.blogspot.com/2015/12/researchspeak-brainhealth-deep.htmlI have hypothesised that they need to be rendered OCB-ve; at present it looks as if neither HSCT, nor alemtuzumab, scrubs the CNS clean of OCBs. Unfortunately, delayed (>10 years) post-treatment CSF studies have not been done. I have been careful to use the term potential cure and not cure; there is an important distinction between the two. If you want to know why ask any oncologists. They stopped using the term cure years ago and now refer to NEDD (no evidence of detectable disease). Regarding HSCT in London. Barts-MS is part of the London HSCT Collaborative Group; Dr Turner sits on the MDT (multidisciplinary team). We refer our patients for HSCT via this MDT; this involves small numbers as most of our patients have disease that is controlled by licensed therapies. I think this is the experience of most MS centres; very patients need to referred for HSCT. http://multiple-sclerosis-research.blogspot.com/2016/02/clinicspeak-london-ms-ahsct.htmlWe simply can't offer HSCT to everyone with MS under the NHS. Like every other mainstream service in the NHS we have to be able to justify it and have a watertight business case. For the latter we need more data and we would also need to do an impact study to see how wider access to HSCT would impact on the provision of this treatment for other conditions, in particular haemoncology patients. It seems as if our discussion is going in circles, so I will signing off on this thread.
I find your thoughts on negative OCB as a possible definition for a cure in MS very interesting. I appreciate the difficulties in getting that data as in the 10 neurologists I saw form being diagnosed with NMO to rediagnosd with MS not once was a lumbar punchure discussed. Many thanks for your insight as always and apologies if you felt I misquoted you. I stand by my original point around alemtuzumab and rebaslining being statistical manipulation, and look forward to your post (if you find the time) on it.
Was the Brain health: time matters report distributed to individual neuro depts, their hospitals or to Trusts? If so, have you received any feedback and have NHS England put any of the recommendations in place?
I asked in reference to the 'what can you do' box. It would be helpful to know whether any neurologist I may speak to in the future had seen the report. If it is unlikely they will have maybe patients could take a print out with them to help the discussion. Or perhaps we should do that anyway.It may not make a difference but pwms could also write to NHS England with their views.
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