Monday, 27 February 2012

Treatment switch for suboptimal response

Rio et al. Change in the clinical activity of multiple sclerosis after treatment switch for suboptimal response. Eur J Neurol. 2012 Jan 31

Background: Therapy for multiple sclerosis (MS) has a partial efficacy, and a significant proportion of treated patients will develop a suboptimal response with first line disease-modifying drugs (DMD). Therapy switch in patients with MS can be a strategy after a treatment failure. We studied the change in clinical activity after switching of first-line DMD because of a treatment failure.

Methods: Relapsing-remitting multiple sclerosis (RRMS) patients treated with interferon-beta (IFNB) or glatiramer acetate (GA) were divided into (i) patients without change in DMD, (ii) patients with a change in DMD because of a poor response, and (iii) those with a change in DMD without relation with response. Annualized relapse rate (ARR) and relapse-free proportions were analyzed.

Results: We identified 923 patients with RRMS. Of the 180 who experienced a change because of suboptimal response, 90 switched to another first-line DMT, 38 to mitoxantrone, and 52 to natalizumab. Median ARR in the pre-DMD period on first DMD and second DMD was the following: 1, 1, and 0 for switchers from IFNB to another IFNB (P = 0.0001); 0.67, 1, and 0 for switchers from GA to IFNB (P = 0.01); 1, 1, and 0 for switchers from an IFNB to GA (P = 0.02); 1.1, 1.5, 0.2 for switchers from IFNB or GA to mitoxantrone (P = 0.0001); 0.9, 1, 0 for switchers from IFNB or GA to natalizumab (P = 0.0001).

Conclusions: In patients with RRMS who have a poor response, switch to another DMD may reduce the clinical activity of the disease.


"This study shows that when first line DMDs (IFN-beta and GA) do not have optimal response it is worth switching to another treatment. As expected, a switch from first line DMD to natalizumab or mitoxantrone was beneficial. But it was interesting that even a switch from one IFN to another IFN, higher and even lower dose, can reduce the relapse rate. It is important to note what treatment failure/ disease breakthrough/ sub-optimal response is considered: a single mild relapse in the first months of treatment does not qualify."

15 comments:

  1. I have PPMS and was given mitoxantron 3 years ago. It made no difference to the progression. The consultant later told me he didn't think that mitox would work for me yet he decided to put me on it. Mitox has bad side-effects and if there was no conviction that it would help curb my progression then I think it was wrong to have put me on it. Now I can't qualify for other trials due to the fact I've been on mitox. This is an example of bad science as far as I'm concerened. Shame on the profession.

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  2. Re: "I have PPMS and was given mitoxantron 3 years ago."

    I am not sure why you were put on Mitoxantrone; there is very little evidence that it helps non-relapsing progressive MS. The only possible exception being if your MRI showed multiple Gd-enhancing or active lesions; in other words your MRI showed evidence of active inflammation. Sometimes clinicians feel they should be doing something rather than nothing; it can be a difficult call. I would prefer to offer someone like you the option of a trial.

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  3. "This is the definition of placebo effect."

    This is the definition of a lazy (trolling?)comment by someone who couldn't be bothered to read the article but has their own agenda (and we all know what that is)?

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  4. "But it was interesting that even a switch from one IFN to another IFN, higher and even lower dose, can reduce the relapse rate."

    Can you explain this without using the term PLACEBO? And then, can you weight your answer against placebo and prove it of, at least, equal probability?

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  5. Re - " I would prefer to offer someone like you the option of a trial."

    If I've been on mitox in the last 3 years can I still get on a trial?

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  6. Is this the same type of placebo effect that could have occurred in

    Beelen R, Maene L, Castenmiller P, Decoene V, Degrieck I. Evolution in quality of life and epidemiological impact after endovascular treatment of chronic cerebro-spinal venous insufficiency in patients with multiple sclerosis. Phlebology. 2012;27 Suppl 1:187-9.

    see recent blog posts.

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  7. Is there any scientific reason why switching IFNs reduces when the switch is to a lower dose?

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  8. MD, if you wanted my opinion you could allow comments on ccsvi posts. Here, i am only questioning the reported effectiveness of a drug change.

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  9. Re: "If I've been on mitox in the last 3 years can I still get on a trial?"

    Mitoxantrone treatment disqualifies you from all the current PPMS DMT trials.

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  10. "MD, if you wanted my opinion you could allow comments on ccsvi posts."

    Sorry VV, this isn't a helpline for the deluded!There's plenty of other places where you guys can share your insights.

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  11. Re: "Can you explain this without using the term PLACEBO? And then, can you weight your answer against placebo and prove it of, at least, equal probability?"

    Yes, the statistical term is regression to the mean or average; i.e. if you select MS'ers because of disease activity their disease is likely to become less active with time.

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  12. Regression to the mean will happen even without a change in treatment.
    I think VV makes a valid point about a placebo effect here

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  13. "you could allow comments on ccsvi posts"

    Yes we could.... and we would get lots of abuse and a variety of threats from misguided people who unfortunately spoil things for others.

    We have alreasy been there and the experiment failed. Research is about learning, we learned from the experience not to invite comments.

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