Sunday, 17 August 2014

ClinicSpeak: switching from interferon to glatiramer acetate

GA has life in it yet. Does long-term safety trump short-term efficacy? #ClinicSpeak #MSBlog #MSResearch

"The following study shows that MSers who are not responding to IFNbeta and are switched to GA have the potential to do relatively well. This open-label study comes quite late in the life-cycle of GA and is unlikely to change clinical practice. Recent data presented at the American Academy of Neurology from MSBase showed that MSers switching from IFNbeta to fingolimod did better on average than patients switching from IFNbeta to GA. If we all adopt treat-2-target of NEDA to try and prevent end-organ damage I suspect very few neurologists and MSers would choose GA, an injectable, over fingolimod, a tablet. What would you do? Some argue that the safety profile of GA is so good who would take a chance of using a newer agent with an unproven long-term safety record? I would also remind you that there are no tests we can do to determine who will be a GA-responder of non-responder. The only way to assess the latter is by putting you on the treatment and monitoring you over a 6-24 month period. The danger of the latter approach is that damage acquired during the observation period of say 24 months is probably irreversible; we know this from the extension studies of numerous phase 3 trials. This post highlights the complexities of MS DMTs and the decision-making that underpins them. It is really a brave new world."


Epub: Ziemssen et al. A 2-year observational study of patients with relapsing-remitting multiple sclerosis converting to glatiramer acetate from other disease-modifying therapies: the COPTIMIZE trial. J Neurol. 2014 Aug 14.

Background: Studies suggest that patients with relapsing-remitting multiple sclerosis (RRMS) who do not benefit from other disease-modifying treatments (DMTs) may benefit from converting to glatiramer acetate (GA). 

Objectives: COPTIMIZE was a 24-month observational study designed to assess the disease course of patients converting to GA 20 mg daily from another DMT. 

Methods: Eligible patients had converted to GA and had received prior DMT for 3-6 months, depending on the reasons for conversion. Patients were assessed at baseline and at 6, 12, 18, and 24 months. 

Results: In total, 672 patients from 148 centers worldwide were included in the analysis. Change of therapy to GA was prompted primarily by lack of efficacy (53.6 %) or intolerable adverse events (AEs; 44.8 %). Over a 24-month period, 72.7 % of patients were relapse free. Mean annual relapse rate decreased from 0.86 [95 % confidence interval (CI) 0.81-0.91] before the change to 0.32 (95 % CI 0.26-0.40; p < 0.0001) at last observation, while the progression of disability was halted, as the Kurtzke Expanded Disability Status Scale (EDSS) scores remained stable. Patients improved significantly (p < 0.05) on measures of fatigue, quality of life, depression, and cognition; mobility scores remained stable. 

Conclusions: The results indicate that changing RRMS patients to GA is associated with positive treatment outcomes.

CoI: multiple

9 comments:

  1. Again, this would be up to the individual concerned... but given that GA is daily s.c. injections, I think the choice would almost always be fingolimod.
    Isn't retention of interferons beyond three years relatively low because of needle fatigue? And that is not daily injections...

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  2. How about a post comparing fingolimod and tecfidera? They seem to both seem to be an intermediate step between interferon/GA and tysabri/alemtuzumab ...

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  3. Prof G,

    Given that highly effective treatments are now available, why would a neuro even consider offering copaxone or one of the interferons? The efficacy of these treatments is moderate at best. It's the equivalent of a car mechanic offering you the choice of drum brakes or disc brakes, or a mobile phone salesman offering you the choice of a brick mobile phone from the 1980s or the latest smart phone. It's almost criminal that neuro are still offering these treatments - I suspect that in some cases it is laziness or too many freebies from the pharma companies. I wonder if this happens in other diseases i.e. The doctors still prescribes the first generation treatments (20 years after being licensed) and not the latest much more effective newer treatments. I wonder if this occurs in arthritis? The issue of safety is a bit of a smokescreen. I'd rather protect my brain and take my chances with a secondary autoimune treatment which in most cases is treatable.

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    1. I was recently diagnosed, and to my astonishment, my neurologist essentially refused to give me anything except the interferons or GA. Her exact reasoning was the "proven" safety point of the injectables, and she thought I was being entirely unreasonable by pushing for the stronger drugs since I don't yet have any serious disability and haven't even tried the injectables. I thought the whole point of the better drugs was to *remain* without any serious disability?

      Needless to say, I'm calling another neurologist to get a second opinion.

      Delete
    2. MS patient on GA here... thought I'd chime in with a situation such as mine, where GA might be an appropriate option.

      Since my conversion from CIS to MS, I've had only one episode, which was over a year ago. MRIs are relatively clean and show lack of progression. My neurologist and I discussed all of the treatment options and standard of care at length at the the time of my diagnosis. I don't have a problem with daily injections and the safety profile of GA/lack of side effects were extremely important to me. If I experience progression/lack of response to GA, I will definitely be willing to take on a little more risk and try one of the newer drugs, but at this stage in my disease, GA (especially with the new 3 times/week formulation) is a treatment that I am happy with. I realize that waiting for the first 12-24 months after starting to see what happens was a risk, but I was more comfortable with that risk than the potential side effects of some of the newer drugs.

      So, to answer Dr. G's question at the beginning of this post... yes - GA's long-term safety did trump short-term efficacy in my decision making process.

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    3. Dear Anon 11.52
      I am happy that you are happy and please do not take offence but it sounds like a Teva rep's response...Teva rep here...please buy my drug.

      Delete
  4. Not everyone tolerates fingolimod. A bad infection and hospitalization would cause someone to think twice. But it's still a good option for many.

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  5. To Anonymous 11:58
    No, actually we do not start with the newest, most expenisve, most fancy drug we have for the treatment of rheumatoid arthritis. Both because of the potential risks, marginal benefits, inconvenience of use ( newer drugs tend to be injectables/infusions) and the cost.
    Newest is not always the best in the pharma world, the molecules are often slightly tweaked when the patent expires and sold at a new price with some new fantastic claims as to efficacy/safety/convenience etc.
    Talking of drugs for arthritis - does anybody remember Vioxx and how it was promoted? And where did it end...

    J.

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  6. I also am on Copaxone and am not a Rep for Teva. After and Extreme initial attack I was wheelchair bound for 3 months. My residual effects are that I have to self catheterize so I chose Copaxone since does not effect your lymphocyte count as other drugs do. You have to get over a period of 6 months until you can judge if it is working which for me has halted relapses and MRI activity.

    Im staying with the daily shots because the trial for the 40mg dose 3 times a week only looked at relapse rate. This does not directly translate to longterm effectivness as has been shown wit h Copacone for more than 20 years.

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