Saturday, 16 September 2017

#NeuroSpeak: biennial neuroinflammation meeting in Keele

How do we balance the risks and benefits of DMTs? #NeuroSpeak

I am on the train travelling to Keele to present a talk on the benefits and risks of DMTs. The challenge is getting the balance right and being able to communicate all the relevant information in 30 mins. Other restraints relate to the fact that it is a pharma-sponsored symposium so I can't talk about unlicensed products and my presentation has numerous disclaimers. 

The core message is that there is increasing complexity in the DMT space with several key attributes to take into account when personalising treatment decisions.  I note that as my talk has evolved on this topic I have dropped the section on the risks of not treating active MS. I should probably include this section in future so as not to upset pwMS who choose not to be treated with DMTs. Other versions of this talk have included slides on HSCT, which is a treatment option in the UK. 



CoI: multiple

19 comments:

  1. Very helpful presentation. Thank you. Waiting for a more complete version including Ocrevus and HSCT. Wonder how many neuros will find your presentation radical :P

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    1. lol wonder how many neuros still believe continuous immuno suppressants won't cause sec malignancies... had that argument with a neuro my partner calls oyster in 2015

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    2. Hope that means they had pearls of wisdom inside.

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    3. lol no it means that they were unnecessarily mean and tried to herd the patient away from a decision by making up crap :)

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  2. Prof G!
    (If patient have posterior fossal, and brainstem lesions and t1 hypointensity with 3,5 EDSS, the switch and prevent to possible rebound is very-very important. This 28 year old patient use Fingo, and her disease seems to be stable but want to be a pregnant,)
    Very complex problem to switch from Fingo to Alemtuzumab. If patient is JC negative, could be switch first from Fingo to Natalizumab, and after to Alemtuzumab.
    It might have a better chance to prevent the MS rebound, and ensure to Alemtuzumab to have a maximal effect.

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    1. I sure you are aware that we cannot comment on individual cases, as this is not the forum to use but switching treatments is a complex issue. There has been a suggestion that fingolimod may influence the chance of alemtuzumab working, so this needs to be discussed with our neurologist. There are a number of posters at ECTRIMS 2017, whether they agree or disaggree will be known when we can see the content on 25th october.

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  3. " The challenge is getting the balance right and being able to communicate all the relevant information in 30 mins"

    Show them this relevant Dmds Neda paper

    RESULTS:

    A total of 99 of 215 patients (46.0%) had NEDA for clinical and MRI measures at 1 year, but only 17 of 216 (7.9%) maintained NEDA status after 7 years. No differences were found in NEDA status between patients with early vs established MS. A dissociation was found between clinical and MRI disease activity. Each year, 30.6% (64 of 209) to 42.9% (93 of 217) of the cohort had evidence of either clinical or MRI disease activity but not both. NEDA at 2 years had a positive predictive value of 78.3% for no progression (Expanded Disability Status Scale score change ≤0.5) at 7 years. Only minor improvement was found in the positive predictive values with additional follow-up of 1 to 3 years.

    CONCLUSIONS AND RELEVANCE:

    NEDA is difficult to sustain long term even with treatment. NEDA status at 2 years may be optimal in terms of prognostic value in the longer term. Our results provide a basis for investigating NEDA as an outcome measure and treatment goal and for evaluating the effect of new MS drugs on NEDA

    https://www.ncbi.nlm.nih.gov/pubmed/25531931

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  4. "but only 17 of 216 (7.9%) maintained NEDA status after 7 years"

    Talk about eficacy

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  5. Thanks Luis. This is very damning of the current neuroinflammatory only model of treatment of MS. RRMS patients should not fear relapses as much as they fear progression. Please, if possible, MD review this paper as this is very disturbing trend and explain.

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    1. No it says that the softly softly approach with low efficacy agents is not what we want...I accept the NEDA rates with HSCT appear to be better than any pharmacological agent, it should be that way as HSCT is the ultimate sledgehammer. I'll have a look and report

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  6. As a layman it's obvious that surpression is less effective than ablation. This is why I have great difficulty reconciling this blog's bias against hsct. I was really re-reading the oldest hsct post on their blood the other week... Those views already seen outdated and shortsighted.

    As hsct becomes a common or garden first line defence, and hopefully as pwMS are treated earlier in their disease, the views of academics and researchers here will seem embarrassingly dogmatic.

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    1. You say "bias against hsct". That's not true I would suggest a balanced view based on the latest available evidence, which continues to be collected and will enable a firm conclusion to be drawn.

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  7. (As the previous commenter said "as a layman") This is not the exact right place to add this comment, but please correct me. B-cell treatments have the best NEDA we have from a drug till now. They work great at RRMS, but no so great at the progressive forms. The drug does not penetrate the BBB, do not affect plasma and I found it hard to find the brain atrophy rates at the official page. I found something between 18-25% b.a. reduction (less than Gylenia). Is it possible that the great progression free rates are coming from protecting the spinal cord but the brain atrophy is the main reason for the secondary progression, so not much can be done with this treatment too to prevent SPMS?
    Doesn't it this make HSCT again the only real answer, where brain atrophy is stabilized?

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    1. Or Alemtuzmab that may be safer than HSCT?

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    2. Maybe less hassle but not necessarily safer

      "In a recent meta-analysis TRM(ortality) was 0.3% in procedures performed after 2005 and nil in patients treated with a low-intensity conditioning regimen. To put these numbers in perspective, TRM in phase II and III studies for alemtuzumab was 0.3%, and the risk of contracting progressive multifocal leucoencephalitis in JC virus-positive patients treated with natalizumab is about 1% per year"

      http://jnnp.bmj.com/content/early/2017/09/02/jnnp-2017-316271

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  8. HSCT can be ablation but it can also be non ablation.


    As to bias against.....you are talking tosh.

    We report on the research news. If there are HSCT papers we report them. There are not many HSCT papers. If there is one I am sure you will alert us to it.

    I don't work on HSCT at the moment and we have not got any money to do so, we have applied for grants with the guys from Sheffield and we have trained staff so the people in Sheffield can do there own stuff. So to suggest bias against is not the case.

    Does the HSCT affect memory cells yes it does and so may answer a question. Do the wonder stories in the media today help your cause...yes they do.

    Is it good reporting no because it lacks balance as it is all fantastic and can't fail but you and I know that it can

    Is it going to change what I do...not yet. If I want human mice it could do.

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  9. "Although NEDA status may strongly predict good long-term outcomes, loss of NEDA status is not necessarily a poor prognostic sign. Clinical experience indicates that patients may have a relapse or new MRI lesion and do well in the long term, and the low NPV of NEDA in our study is consistent with this. Studies27,28 have suggested that inflammatory activity in MS does not always correlate with the rate of later disability progression."

    So is Neda useful?

    You tell me

    Obrigado
    http://jamanetwork.com/journals/jamaneurology/fullarticle/2048956

    Who

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