Wednesday, 9 January 2013

Treat-2-Target: NEDA (no evidence of disease activity)

"I would appreciate your comments on the following beta version of a treatment or monitoring algorithm for relapsing MSers. The idea is to adopt the strategy of treating-2-target; the target being NEDA or no evidence of disease activity. This approach has being adopted from the rheumatologists who developed this strategy about 15 years ago to treat rheumatoid arthritis (RA). In general, rheumatologists treat RA very early, and very aggressively, and escalate treatment rapidly to the more active biological therapies if there is no response to 1st-line treatments. Their aim is to prevent joint damage occurring from ongoing inflammation. This approach has worked for RA very well; there has been a major drop-off in RAers needing joint replacements. The difference between MS and RA is that we don't have the option of replacing the brain and spinal cord; there is no fall back option for MSers."

"The aim of the algorithm is for neurologists to do the same for relapsing MSers as rheumatologists do for RAers. If we adopt this active/aggressive approach will MSers do better when compared  to MSers managed more conservatively or less actively, for example allowed to have disease activity on 1st-line therapies or have a significant delay when starting treatment? We won't know unless we try! The problem is getting the MS community to move in this direction and to make sure we all monitor the MSers in our care or at least provide them with the tools to monitor themselves."

"Neurologists are generally quite a conservative bunch, whereas rheumatologists have always been more aggressive. I think this relates to rheumatologists having had DMTs for several generations. May be the field is ready for a change?"

16 comments:

  1. I had a little activity of rrms on copaxone still, particularly in the first three months but then a little calmer and also some "subclinical" activity which I did sort of notice (felt like waves of inflammation coming and going - have experience of this due to juvenile polyarthritis in the past). At the end of month 3 (more active phase) I was offered to go on Tysabri but felt it was too dangerous (because of its potentially deadly/irreversible side effects) but opted for Gilenya about six months later when it became available, although ms activity had calmed down, but not as much as I thought was good by then. I think I went onto G as a case of active rrms rather than highly active - and I am glad I did and my neuro "let" me even though I am her first patient on it. Btw I feel that maybe Gilenya/fingolimod does not quite belong in the same group as natalizumab/mitoxantrone - they seem stronger and (so far) more dangerous to me ... and it seems some docs/patients feel the same as I hear plenty of anecdotal evidence of people getting Gilenya/fingolimod as first line.

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    1. Unfortunately, fingolimod is not licensed as a first-line treatment in Europe. In the UK we can only use it second-line in MSers who have failed interferon-beta.

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  2. I don't quite get the logic, if you are a no responder to current 1st line and you do ´t have a very active disease then why contiune your treatment? and how do you know that someone is a no reponder if they are disease free? furher more shouldn´t the nab+ve test be in the the no responder arm/leg..if the treatment is working why test for nabs..
    Also I´m missing the probably MS entrance, I'm not quite sure on how its related to CIS but I think you can find it in the Mc´Donalds criteria. my neuro told me they are not the same..
    I suggest you rethink the right part of your chart with the first line treatments and I don´t get the SPMS loop, it just seems to shorcut itself.
    Perhaps we can discuss this on MS Research day..
    Best wishes
    //Swedish Sara

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  3. This is really helpful for me, thanks. I have long assumed that when you talk about early aggressive treatment, you meant RRMS? >>> Alemtuzumab. But it looks like you think there is still a role for 1st line therapies, with 6-12 months of treatment to see if one is a responder. That's good to know.

    I know my neurologist (in the U.S.) will first line natalizumab for new diagnoses who have evidence of a lot of disease activity. But not me.

    This makes me feel a lot better about taking Copaxone for now. Maybe I'm not missing out while my disease smolders away after all?

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    1. Horses for courses. Some MSers are risk adverse and some have a good prognostic profile and don't want to take the chance of developing side effects from an aggressive therapy and would prefer to see how they do on a 1st-line treatment.

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  4. I think the chart is too complicated but as far as I understood it is a good idea to assess after 6-12 whether the treatment works and if not to escalate. In my particular case I get relapses but they are not detectable on MRT so my guess is they happen in the grey matter but it's extremely difficult to convice neuros of that so I stick to fumarate for the time being (although they would prefer the old route of interferons and GA). Not idea what to do???

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  5. the very right hand side of this algo is a closed loop!

    but the idea is there...

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    1. Are you sure? You can get out if you develop, NABs, are a non-responder (active or highly-active disease) or enter the non-relapsing secondary progressive phase of the disease (no licensed treatments at present).

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  6. Who is going to decide active or highly active disease? Would there be set criteria, or would it be down to the individual neurologist to decide?

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    1. In the UK NICE have defined two groups of so called "highly-active" MS:

      Natalizumab (Tysabri, Biogen Idec and Elan Pharma International Ltd) has a marketing authorisation as a single disease-modifying therapy in highly active relapsing–remitting multiple sclerosis for the following groups:

      • Patients with rapidly evolving severe relapsing–remitting multiple sclerosis defined by two or more disabling relapses in 1 year, and one or more gadolinium-enhancing lesions on brain MRI or a significant increase in T2 lesion load compared with a previous MRI. This patient group is referred to as the ‘RES group’.

      • Patients with high disease activity despite treatment with beta interferon. This group is defined as patients who have failed to respond to a full and adequate course of a beta interferon. Patients should have had at least one relapse in the previous year while on therapy, and have at least nine T2-hyperintensive lesions in cranial MRI or at least one gadolinium-enhancing lesion. This patient group is referred to as the ‘suboptimal therapy group’.

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  7. Re 'Radiologically Isolated Syndrome' - will these be detected by chance during MRI scans for other problems?

    What decides if there is a 'High risk of conversion' for RIS & CIS?

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    1. Yes, RIS is picked-up by chance when scans are done for another reason. In some countries people with RIS are on DMTs. This would not be possible in the UK.

      The best predictor of conversion from RIS/CIS to MS is the lesion load and/or the presence of active Gd-enhancing lesions.

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  8. The chart really demonstrates the lack of treatments for SPMS after all those loops and possibilities for RRMS.
    Lousy disease.

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  9. Is this done with UK NHS/NICE policies in mind?
    It would be better to have a general 'ideal' algorithm. Whether or not you can follow it is a different matter. It could be modified for diffenent systems or countries.


    There are pathways leading to 'escalation therapy'. No pathway for 'induction therapy'? Some patients will certainly be willing.


    Diagrams for computer program algorithms are quite standard. I don't know if there is any standard protocol for diagrams of medical algorithms.
    But I think the flowchart has some problems - for example, it uses rectangles both for 'events' (e.g. CIS) and treatment decisions (e.g. first-line therapies

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    1. Page 4 of this document has a better flowchart
      http://www.psycard.com/psycardservice/admin/UploadArticleFiles/2009531161955890.pdf

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    2. I agree, much better. This is a beta version. I plan to make this algorithm interactive and with more content! But I need some IT help; I simply don't have the time to code it myself. Any volunteers?

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