Friday, 8 September 2017

Think before you switch. Think before you start.

Yamout BI, Said M, Hannoun S, Zeineddine M, Massouh J, Khoury SJ. Rebound syndrome after teriflunomide cessation in a patient with multiple sclerosis. J Neurol Sci. 2017 Sep 15;380:79-81.
We report a case of relapsing remitting multiple sclerosis (RRMS) with severe rebound syndrome 12weeks following discontinuation of teriflunomide therapy. The patient developed severe clinical relapses with significant increase in the number of brain and spine magnetic resonance imaging (MRI) lesions. She responded well to intravenous and oral steroids and was later maintained on rituximab.


DMTs stop relapses and so if you stop your DMT, relapses can come back. 

If they come back with a vengeance, Neuros call them rebounds. They are becoming increasingly associated with drugs that inhibit migration. Stop the drug and the pathogenic cells are there. Teriflunomide is not a migration inhibition drug. 

So if you switch from teriflunomide this is something to think about.

You have been asking about features that help you select a treatment. 

Obviously there is safety, efficacy and convenience but before you start a drug you need to consider how you will end that drug. 

What will you switch to? and how long will be the wash out before you start the new one? and how quickly does the new on take to work? 

In this case 12 weeks was too long a wait.

25 comments:

  1. "DMTs stop releases". Do you mean "relapses"?

    Also DMDs don't stop relapses, they sometimes lessen, sometimes reduce.

    One of the main reasons I refused DMDs is because I asked myself "what would make me stop"?

    You just bounce from one drug to another, caught in the cycle of dependence and fear of stopping due to rebound.

    ReplyDelete
    Replies
    1. I am now convinced you are deluded. Don't you realise HSCT is also a DMT. HSCT is not a cure, most people eventually have a return of disease activity given sufficient time.

      Delete
    2. You didn't have to, all your previous posts indicate your direction of travel.

      Delete
    3. I've had ms for 15 years. I made the decision to avoid dmd's before I even knew what hsct was. For precisely the reason I mentioned.

      Delete
    4. I agree with Anon that HSCT is nothing but a potent DMT. The stem cells are given to help your bone marrow recover from aggressive chemotherapy.

      Delete
    5. I am fully aware of how hsct works and it's various components. I am aware that many post protocol drugs are the same as regular dmd's. But I also believe that dose and intensity is vital for tipping the balance in favour of ablation.

      Delete
    6. If you tar your flag to mast, it sticks....I'm afraid.

      I can change predictive text and spelling so no-one understands the whinge;-)

      Delete
    7. Give that ablation is different from suppression. I'm not sure the conclusion your draw or parallels between hsct and dmd's is valid.

      Delete
    8. Given that both ablation and depletion with agents such as rituximab, alemtuzumab and cladribine or mitoxantrone etc are essentially the same, the only difference is the repopulation kinetics ie with stem cells or allowing repopulation to occur naturally.
      So the parallel is valid

      Delete
    9. I don't agree with that. The chemotherapy is a crucial difference. I'm not sure where the hostility to something that clearly follows logic of existing treatments, comes from.

      I stayed away from dmd's before I knew about hsct, because of the rebound and lack of convincing NEDA.

      I support hsct for the same reasons. To be hsct is a logic step on from dmd's. As this very site has stated 'hit ms hard and early'.

      Delete
    10. Cladribine and mitoxantrone are chemotherapy agents, the monoclonals essentially achieve the same thing and were originally used for leukaemias, the difference with HSCT is in how aggressively they are used. So, it's a question of degree essentially.
      Surely that isn't too hard to understand?

      Delete
    11. Absolutely agree. Its a question of degrees. Hence confusion over the contradiction that is "hitting MS hard and early" (backed by plenty of research, as well as this site)... but then promoting DMDs over HSCT.

      Hitting MS hard and early.
      Suppression over ablation.

      ... there is a rather basic contradiction there.

      Delete
    12. Not a contradiction, a range of options.

      Delete
    13. Hsct is also use for:
      Severe Aplastic Anaemia
      Autoimmune Diseases
      Acute Leukaemia
      Lymphoma
      Solid Tumours

      Delete
    14. Re: "but then promoting DMDs over HSCT."

      It is about promoting first-line and/or licensed treatments. HSCT is not licensed and we can't use it first-line. It is about the reality on the ground in the NHS.

      We use HSCT when it is indicated.

      Delete
    15. The more dmd's are prioritised over hsct, the harder licensing will become and good data. You're way too intelligent to not see that.

      Reality on the ground does not justify a laissez faire approach to the pain people live with every day.

      Delete
    16. "It is about promoting first-line and/or licensed treatments."

      But some Dmd recently approved are class 2 evidence and they did´nt had the gold standart ,Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial that you are allways talking about

      Delete
    17. Klaus SchmiererTuesday, September 05, 2017 8:18:00 pm

      We have been using various drugs based on phase II evidence,

      Obrigado
      Luis

      Delete
    18. Re: "It's about promoting first-line and/or licensed treatments. HSCT is not licensed and we can't use it first-line. It is about the reality on the ground in the NHS."

      It sounds like the NHS is being a bit too passive and would be wise to license HSCT. It may save the NHS money in the long term.

      Delete
    19. some agents you cant blind e.g alemtuzumab as it causes infusion reactions

      Delete
  2. I think Prof Gavin just said "horses for courses" some horses don't want to be disappointed when the percentage that don't respond to DMT is them. I don't live in fear by taking a DMT - I live in hope that I am going to keep galloping. Bearms like many before them are not deluded but they have a propositional fallacy (affirming the consequent).

    Ps grammar pedants I am using the gender neutral pronoun ;)

    ReplyDelete
    Replies
    1. A propositional fallacy is an error in logic that concerns compound propositions. In order for a compound proposition to be true all the simple propositions in it have to be true and validly related as the logical connector (, , , , ) suggests.

      Delete
  3. Why do a washout at all? With different mechanisms of action and similar few month washout and effectiveness timescales, why not just switch immediately and let the lingering effects of the first bridge to the second?

    ReplyDelete
    Replies
    1. if you have pre clinical PML and you delpete the immune system there is no way back...there have been deaths because of this

      Delete

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.