Thursday, 2 October 2014

Long-term effect of Copaxone

This retrospective cohort study from Spain aims to analyse the long term outcomes of patients on Copaxone. 

The main headline findings are the following

  • 85% of patients remained free from disability progression (as measured by EDSS)
  • Stable EDSS over the study period (i.e. no significant change from the beginning to the end of the period)
  • Reduction in annual relapse rate 
  • Reduction in T1 Gadolinium enhancing lesions

What does all this mean?

Well at first glance, if I were on Copaxone I would feel pretty reassured by this data but there are a number of factors to consider when looking at the small print. 

Firstly, this study was funded by Teva. Who are Teva I here you ask? Well they are the manufacturers of Copaxone with a vested interest in demonstrating the efficacy of their drug. 

Secondly, (see my previous post on cohort studies) this is a retrospective observational study which comes with its own limitations - we are relying on case note review which is often unreliable

Thirdly, there is no control group to compare with which can be problematic

The study defines 'clinical effectiveness' as being disability free for 5 years but we must remember the natural history of MS - it can take many years to go from RRMS to SPMS and therefore these people may have been simply captured early in their disease course. This becomes more relevant when one thinks about the fact by 9 years follow-up, the study only had data on less than 50% of the cohort.

The MRI data is also a cause for concern - comparing Gd-enhancing lesions from onset of treatment to last date of follow up is deceptive; these lesions do not represent long term acquired disability but recent areas of inflammation. Indeed, we would expect less of these in any case at the later stages of MS as relapses tail off and disability builds up. 

All in all, this is an interesting study, however I would have liked to have seen it done by an independent group who did not have a vested interest in Copaxone. 

Arnal-García C, Amigo-Jorrin MD, López-Real AM, Lema-Devesa C, Llopis N, Rosa RS; XPERIENCIA-5 Study Group. Long-term effectiveness of glatiramer acetate in clinical practice conditions.

J Clin Neurosci. 2014 Sep. pii: S0967-5868(14)00490-1. doi: 10.1016/j.jocn.2014.05.045. [Epub ahead of print]

Glatiramer acetate currently represents one of the main treatments for relapsing-remitting multiple sclerosis (RRMS). However, the information available about its long-term effect in clinical practice is still limited. Thus, this multicenter retrospective cohort study aimed to assess the long-term effectiveness of glatiramer acetate in this setting. 

The study population included RRMS patients treated with glatiramer acetate for at least 5years after its marketing authorization and the primary endpoint was long-term clinical effectiveness, defined as absence of disability progression for at least five consecutive years. A total of 149 patients were included into the study, who had received glatiramer acetate for a mean of 6.9±1.4years (5years, n=149; 6years, n=112; 7years, n=63; 8years, n=32; 9years, n=21). 
More than 85% of patients remained free from disability progression through years 1 to 9 of glatiramer acetate treatment, and 75.2% showed absence of disability progression for at least five consecutive years. Expanded Disability Status Scale (EDSS) scores were maintained, with most patients showing stable/improved EDSS and 92.6% sustaining EDSS <6. Decreased annual relapse rates and increased proportion of relapse-free patients were maintained during the whole glatiramer acetate treatment compared to the year prior to its authorization (p<0.001). The number of gadolinium-enhanced T1-weighted lesions also decreased from pre-glatiramer-acetate assessment to last follow-up whilst on glatiramer acetate (p<0.05). 
In conclusion, administration of glatiramer acetate shows long-term clinical effectiveness for RRMS treatment; its effect under clinical practice conditions slowed disability progression and reduced relapse occurrence for up to 9years.


  1. Does that mean we cant believe any of your findings because of team gs vested interests?

    1. Any conflicts of interest team G may have are clearly stated. You can make up your own mind on whether you believe any findings or not.

  2. No, it just means you need to look at these things with a critical eye and evaluate as appropriate. Which is why I said it would have been better if the study had been carried out independently.

    1. There seems to be an uncritical eye with the drugs used where Team G has a financial interest:

      So tell me, why does the Copaxone trial necessitate your critical eye where the Alemtuzumab doesn't? They are both open label, retrospective trials.

  3. And if you scroll down the article, it clearly states COI-Multiple.

    1. And if you look at the sponsors for the Alemtuzumab trial, it is Genzyme.


    2. Well seeing as they make Alemtuzumab that's not exactly earth-shattering.
      A difference in the 2 studies is that for the Copaxone study above, some of the authors are direct employees of Teva, the manufacturers of Copaxone. Not sure that this is the case for the Alemtuzumab trial you quote but if there are and it is clearly stated then you can make your own mind up.
      A full list of Team G's potential conflicts of interests (funding etc) can be seen if you click the conflicts button at the top of the page.

    3. The sudy that this post is about has similar conclusionsituation to the longterm extension study of the pivotal trial for Copaxone:

      Since none of the authors are direct employees for Teva either as you proclaim for the Alemtuzumab trial, then the results of either trial cannot be questioned according to your logic.

      As a Copaxone users I am glad that the latest analysis gives credence to the effectiveness of Copaxone. As for Team G's analysis, the biased conclusions raise question about motives.

    4. Look, you make up your own mind as to how independent/partial the studies are. COI statements help you to do this.
      You seem quite keen about Copaxone but can we be sure you don't work for Teva?
      If you believed everything that Copaxone is claimed to do, I'm surprised it hasn't been claimed to be a cure for Ebola!

    5. You might want to look at the Charcot project to cure Ebola since this disease as well as MS is caused by a virus. If only the lemmings would see the light!

    6. Oh that made me laugh .. Copaxone as an add on therapy to cure Ebola, I can see it now. While I don't want to add any fire to this discussion, I will say that I injected copaxone for four years, and it made not a jot of difference, except some bad injection site reactions, tiredness and weight gain (went up to UK size 16/18) Since stopping it some four years ago, no tiredness, no lipatophy and all weight lost (back to UK size 8, hurrah) And the MS is same as prior to and on copaxone. What works for some, doesn't for others.

    7. "You might want to look at the Charcot project to cure Ebola since this disease as well as MS is caused by a virus."
      I think a vaccine against Ebola would be more efficacious (currently in development I understand). On a similar note re Charcot project, I've alsways wondered why there isn't a vaccine against EBV, it's not as if it's a trivial disease for some and if it was the cause of MS, then over time (probably 30 years or so) you'd expect to see MS gradually die out in EBV vaccinated populations. It'd put us all out of a job but I'd willingly accept that and how great would that be?

    8. Anonymous 2.11 pm
      Glad you got a laugh!
      Careful you don't upset our visitors from Teva!

  4. not sure what you mean the in financial interest in alemtuzmab are you profGs stock broker

  5. Prof. G and Mouses 1 and 2 have worked very hard over the past few years to teach us how to read these studies more closely. Even with COI's, this paper has some very concerning data loss between year 1 and year 9. In fact 6 of 7 subjects are gone. Where did they go? Does their disappearance relate at all to them not doing so well on Copaxone? Did those 6 subjects get dropped when they failed Copaxone? Could there be some cherry picking going on here? Even if this paper was written by a marketing intern at Teva, it's conclusions still seem weak.

    I really appreciate these kinds of posts, Arie. Because, later someone is going to send me a magazine article about how almost nobody gets disabled on Copaxone, and it will conveniently leave out the attrition data.

    As for Team G's credibility, there are plenty of other MS bloggers out there ready to call foul on their mistakes. Moral of the story? Read widely.

  6. "As for Team G's analysis, the biased conclusions raise question about motives".


  7. It looks like Copaxone can take up to 6 months to become effective. This can be problematic for those who have active disease since they are likely to stop before this time. But it is good to know that if you can stick with it, it will likely halt disease progression as 53% had stable or improved EDSS score and 65% did not transition to SPMS after 15 years of continuous use.

    This is comparable to the 5 year results of the Alemtuzumab trial. The difference being there is a percentage of people that need to be retreated (some several times) to stabilize the disease.

    Since the goal of Team G is to achieve NEDA, Alemtuzumab would look very ineffective if it was judged after one treatment. After all, if you are not NEDA damage is ocurring and thus the therapy is a failure per the Team Dogma.

    So yes a critical eye needs to be used when evaluating data and comments presented on this site.

    1. As we don't have long-term data for Alemtuzumab treated MSers compared to this Copaxone study the jury is still out on Alemtuzumab's efficacy in slowing progression long-term.
      My money would be on it (and the other HEDMTs) being superior but we'll have to wait and see.
      This study has MSers who have received Copaxone for a number of years so, for this group it must be doing something as they wouldn't still be taking it ie enriched for responders. It fails to take into account the large numbers for which Copaxone does little or nothing.


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