Saturday, 19 September 2015

ClinicSpeak: 5-year extension data for fingolimod

Fingolimod seems to be doing the job. Why can't we have it 1st-line? #ClinicSpeak #MSBlog #MSResearch

"The following paper describes the long term (5-year) extension results of the fingolimod trials. As expected MSers are doing very well with a significant proportion free of clinical and MRI activity. It would be helpful to know how many are NEDA after rebaselining at 12 months. I note that about 1 in 10 of treated subjects withdrew due to adverse events; this is quite high. It would be interesting to know how many withdrawals were due to opportunistic infections the most worrying emerging adverse event with fingolimod. On balance fingolimod seems to have an acceptable benefit:risk profile; it is a great pity we can't use it first-line in Europe. I suspect MSers living in countries where  a significant proportion of treated with fingolimod first-line will do better than average than MSers living in countries where access to the drug is second-line. The reason why I say this is that fingolimod is the oral agent with the greatest impact on end-organ damage (brain atrophy). The data that is emerging linking brain atrophy to cognitive impairment and poor outcome in MS is very compelling. Who wouldn't you want to slow your rate of MS-related brain atrophy down and preserve brain? It is a no-brainer!"



Background: Fingolimod safety and efficacy data in relapsing-remitting multiple sclerosis (RRMS) are available up to 5 years, from an extension of a randomized, placebo-controlled, double-blind, phase 2 study, at a dose higher (5.0/1.25 mg) than the approved dose of 0.5 mg. 

Objective: The objective of the study is to present the end-of-study data (>7 years) from the open-label extension of the phase 2 study. In the core phase (6 months), patients (N = 281) were randomized to placebo or fingolimod 1.25/5 mg. In the extension, placebo patients were randomized to fingolimod 1.25/5 mg. 

Methods: All patients received open-label 1.25 mg fingolimod after month 24 and 0.5 mg after month 60. Clinical visits were performed every 3 months, expanded disability status scale (EDSS) every 6 months and magnetic resonance imaging (MRI) annually. 

Results: 122 (48.8 %) patients completed the extension study; overall fingolimod exposure was 1230.7 patient-years. The most common (>10 %) reasons for study discontinuation were adverse events (19.6 %) and consent withdrawal (16.4 %). Fingolimod treatment for >7 years was associated with sustained low clinical and MRI disease activity. Over 60 % of patients remained relapse free and about 80 % were free from any MRI activity. Overall annualized relapse rate was 0.18. Long-term fingolimod treatment was not associated with new safety concerns. 

Conclusions: Long-term fingolimod was well tolerated and associated with a sustained low level of disease activity.

CoI: multiple

14 comments:

  1. 80% MRI activity free va 60% relapse free kind of strikes me .. How common are relapses with no associated MRI changes ?

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  2. "Who wouldn't you want to slow your rate of MS-related brain atrophy down and preserve brain? It is a no-brainer!""

    On the surface, nobody wants to progress but those patients and Neurologists who look at the current crop of DMD's and don't jump on the bandwagon does not mean they do not want to stop the disease. It just means they don't consider themselves innovators as you do in the hopes a real solution will become available.

    http://www.ncbi.nlm.nih.gov/pubmed/22383793

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  3. Comparing the 15 year extension study of Copaxone, it seems Copaxone has surpassed the effectiveness of Fingolomod at 5 years:

    "For Ongoing patients, annual relapse rates (ARRs) maintained a decline from 1.12 +/- 0.82 at baseline to 0.25 +/- 0.34 per year; 57% had stable/improved EDSS scores (change < or = 0.5 points); 65% had not transitioned to secondary progressive multiple sclerosis (SPMS); 38%, 18%, and 3% reached EDSS 4, 6, and 8."

    http://www.ncbi.nlm.nih.gov/pubmed/20106943

    Sinc e theses are both open label observational studies how can you come to the conclusion that Fingolomod is "highly effective"?

    Since Copaxone has a better safety record including its effect on pregnancy, one has to wonder what is driving your bias.

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    Replies
    1. If you compare apples with pears you get lemons the people going into copaxone trials 15 years ago are different from people going into tials 5 years ago....

      What is driving our bias....reading and digesting...what is driving yours?....Teva rep?

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    2. Yes, the people on Fingolomod are different people and no doubt not treatment naive so the question is why isn't Fingolomod vastly superior at 5 years compared to single agent patients continuously on Copaxone for 15 years?

      So, I guess if someone questions the logic of Team G, they must be a Teva rep? Interesting conclusion and it is not a surprising retort for someone who has to be on the defence when marketing new DMD's.

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    3. Questioning logic of TeamG......You don't have to be a TEVA rep but it helps when dealing copaxone:}.

      As you your claim about marketing new DMD you can see my conflicts/

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    4. It doesn't matter what your conflicts are you are part of Team G which has one voice, one opinion, one mind.

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    5. RE: "It doesn't matter what your conflicts are you are part of Team G which has one voice, one opinion, one mind."

      MouseDoc and I often have different opinions about things; for example I am supporter of the viral hypothesis of MS, MouseDoctor is a sceptic. Debate and more debate is good for science. Having one mind is not good. We don't agree on a lot of things.

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    6. Interesting, differing views on MS etiology. MD if you are a viral skeptic what is your countering opinion on the MS trigger?

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    7. I think Prof G means is the target for MS a virus (all the time)-ProfG view) or is it a virus trigger to drive autoimmunity (rest of the World view).

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    8. You guys must debate in private because what comes across is everyone is in lockstep agreement. I suspect Mouse doctor fears for his job if he publicly goes against the grain.

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    9. Re: "You guys must debate in private because what comes across is everyone is in lockstep agreement."

      You obviously missed our online debate on the outcome of the fingolimod PPMS trial.

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    10. ProfG likes to make his views public and if wrong is prepared to take the resultant abuse, coming his way. I on the other hand prefer the silent approach....it makes life simpler

      However, we do debate in private...it's called talking and listening and if we send too much of a mixed message it is simply going to be confusing...is MS wasn't confusing enough already.

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