Thursday, 29 June 2017

My drug is better than low hanging fruit. Rituximab better than CRAB

Spelman T, Frisell T, Piehl F, Hillert J.Comparative effectiveness of rituximab relative to IFN-β or glatiramer acetate in relapsing-remitting MS from the Swedish MS registry. Mult Scler. 2017 Jun 1:1352458517713668.

OBJECTIVE:To compare treatment effectiveness and persistence in relapsing-remitting multiple sclerosis patients who initiated rituximab versus glatiramer acetate (GA) or interferon-beta (IFN-β).
METHODS:A total of 461 patients from the Swedish MS registry in the rituximab arm were propensity score matched on a 1:2 basis with 922 patients from the IFN-β/GA comparator, between April 2005 and November 2015. Annualised relapse rate (ARR) was compared using the Poisson method. A marginal Cox model was used to analyse time to first relapse, 3-month confirmed disability progression and treatment discontinuation in the matched sample. A signed-rank test was used to compare Expanded Disability Status Scale (EDSS) change from baseline.
RESULTS:Rituximab was associated with a reduction in ARR (0.003; 95% confidence interval (CI) = 0.001, 0.009) relative to IFN-β/GA (0.026; 95% CI = 0.020, 0.033) ( p < 0.001). Rituximab was associated with an 87% reduction in the relapse rate (hazard ratio (HR) = 0.13; 95% CI = 0.04, 0.41) and an 85% reduction in the discontinuation rate (HR = 0.15; 95% CI = 0.11, 0.20) relative to IFN-β/GA. EDSS regression from baseline was greater in the 

rituximab group at 12 and 24 months.
CONCLUSION:Rituximab appears to be superior to first-generation disease-modifying treatments (DMTs) with respect to relapse control and tolerability, whereas superiority on disability outcomes is less clear.


I tear my hair out when a DMT is tested against a placebo, meaning in this day and age it is oK to give someone nothing, when you have nearly twenty active treatments. 

The next worse thing is that you test your agent against placebo-plus. 

No disrespect to people taking beta interferon or copaxone as they are the Worlds most popular treatments, but we know their level of efficacy. It is not high and to test rituximab against beta interferon or copaxone is a non-contest. 

Howeve,r it may lose if we look at the  side -effects  as the outcome as the CRAB drugs are well tolerated

We can do an off-label assessment against a CRAB, but why not do the rituximab against fingolimod, or alemtuzumab and give the drug a run for its money.

The ethics committees/funders need to get some jajce (eggs) to stop these practice of placebo controlled relapsing MS trials. I know it makes it easier to get a result  

However, if this particular case it was not a trial of one verses the other it was assessing in real life. For every one rituximab pwMS they selected to control it with 2 people taking CRAB

10 comments:

  1. This is very sad, it's not only sad that brave people are wasted as unnecessary test cases but also sad that we are still working on DMTs that we must know are less effective than current market leaders.

    ReplyDelete
    Replies
    1. Please note these people are assessed by their presence in a registry, it is not a formal clinical trial and I guess people taking beta interferon chose to have this drug.

      I think my post was misleading and I will change it

      Delete
    2. Most people are totally ill informed. Nobody would take something as utterly worthless as beta interferon or glatiramer acetate if properly educated, especially as most brands of it must be painfully injected.

      Delete
    3. If most patients are ill informed, and drugs are the most popular MS sellers world wide, then what does that make the neurologists?

      I can't help it, even though I have personally met 2 neurologists who are good doctors, the 6 I have met who are poor excuses for human beings let alone doctors always make me enjoy some good ole 'neuro bashing'.

      Delete
  2. Replies
    1. https://www.dropbox.com/s/11rmqwwfd2yevxs/1352458517713668.pdf?dl=0

      Delete
    2. I think this and other studies in Sweden are being done because there is a debate going on in Sweden weather or not it is legal to use Rituximab as a DMT. Big pharma is saying no... there not so much funding going on so you can make a proper trial. So they are using our MS-register to try to prove the point that Rituximab is good enough. It's the most used DMT i Swezen right now. So I must say that I think you missed the point on this one MD... one of the reasons so many people still ate taking CARBS is sadly because they do what their neuros tell them and all neuros aren't of the same opinion. You can see a clear difference between the north and south of Sweden. That might also be way they are comparing them, to put a bit leverage so more people can be prescribed Rituximab... I think it's a good thing they are doing in taking on Big Pharma. It would be a sad day for us in Sweden if we where to lose the right to prescribe Rituximab.

      Delete
    3. Thanks a lot ...Prof. Baker... truly appreciate...Luis

      Delete
  3. If I type jebem ti jajce will this get published?

    Lol foreign swear words aside, my partner's breast cancer treatment was paid by a clinical trial 10 years ago, which was testing the then best treatment tamoxifen v. what they hoped would be the new best treatments.

    In my mind, it is a travesty that the ms world is doing AND accepting placebo and low efficacy drug trials. I honestly believe that anyone who does a placebo trial for MS dmts at anytime between 2012 and today should be put into jail.

    Unfortunately, I'm not the judge and the executioner.

    ReplyDelete
  4. Yesterday i was in an consultation with hematologist she does 60 Ahsct per year mostly for malignacies
    She said that in her experience with rituximab even at low doses 100mg 4 to 6 days course the cd20 b cells are completely wipe out for a long time .Also i talk to her about b cell overshoot in Ahsct and Alemtuzumab and taking rituximab to prevent that overshoot she said that it seen to be not much of a consensus regarding that.
    Since your immune system already depleted you should be carefull not to over depleted further wich can cause you problem in the long run

    ReplyDelete

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