Is a "trend" in beneficial results less impressive than regular stastically significant results? That word "trend" worries me.


Neurology. 2007 Mar 20;68(12):939-44.

Randomized, double-blind, dose-comparison study of glatiramer acetate in relapsing-remitting MS.

Cohen JA, Rovaris M, Goodman AD, Ladkani D, Wynn D, Filippi M; 9006 Study Group.
Mellen Center for MS Treatment and Research, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. cohenj@ccf.org

OBJECTIVE: To evaluate the safety, tolerability, and efficacy of glatiramer acetate (GA) 40 mg daily vs the approved 20-mg formulation in relapsing-remitting multiple sclerosis.

METHODS: Eligibility criteria included clinically definite multiple sclerosis, Expanded Disability Status Scale score 0 to 5.0, no previous use of GA, at least one relapse in the previous year, and 1 to 15 gadolinium-enhancing (GdE) lesions on a screening MRI. MRI was repeated at months 3, 7, 8, and 9, and neurologic examinations were performed at baseline and months 3, 6, and 9.

RESULTS: Of 229 subjects screened, 90 were randomly assigned to GA 20 mg (n = 44) or 40 mg (n = 46). The groups were well matched at baseline for demographic, clinical, and MRI characteristics. The primary efficacy endpoint, total number of GdE lesions at months 7, 8, and 9, showed a trend favoring the 40-mg group (38% relative reduction, p = 0.0898). A difference between the two dose groups emerged as early as month 3 (52% reduction; p = 0.0051). There was a trend favoring the 40-mg group for relapse rate with benefit on proportion of relapse-free subjects (p = 0.0183) and time to first relapse (p = 0.0367). GA 40 mg was well tolerated, with an overall safety profile similar to that of 20 mg. Some features of injection site reactions and immediate postinjection reactions were more common and severe with the higher dose.

CONCLUSIONS: Glatiramer acetate (GA) 40 mg was safe and well tolerated. The overall efficacy results suggested that a 40-mg dose of GA may be more effective than the currently approved 20-mg daily dose in reducing MRI activity and clinical relapses.
PMID: 17372130 [PubMed - in process]

Wannabe,

These days, when a drug company wants to show some kind of positive result for a MS medication, it hires the Cleveland Clinic to run the trial !

I agree....the word "trend" is troublesome...if you can't statistically prove something, using this word is a nice alternative. I also notice how they "gloss over" the site reaction results from the higher dosage....."Some features of injection site reactions and immediate postinjection reactions were more common and severe with the higher dose." Lipoatrophy can be a big problem for many patients using Copaxone so why didn't they elaborate more on this by giving more detail and percentages?

Many of us have read what the Cochrane Group's opinion of Copaxone states...not effective in the treatment of MS.... makes you wonder why they are doing an open label trial by doubling the dose. I also would like to know if by doubling the dosage, the patient has to pay double the price!!

I'm thinking this is a Teva marketing department's attempt to bolster the market share of Copaxone in the very lucrative MS drug market.

Harry

Hello,

My fiance has choosen to be past of this study.

I use C and LDN and usually do C every other day. That creates a nice little "stash" of C. So, every now and then, I double up and inject twice a day.

Symptom-wise, I saw no difference between 1x, every other day or 2x, though.

Z

I would imagine that this would have no impact on symptoms since copaxone wasn't developed to impact symptoms at all, only slow the progression of the disease. So changing the frequency of injections "now and then" probably wouldn't be noticeable unless you seemed to develop new disease activity or something like that. But since Copaxone isn't supposed to affect existing symptoms, I don't think that should be your measure of how your chosen and variable dosing schedule is affecting you.

Probably simply a matter of semantics, but, if the disease progression is slowing, then sx manifestation will also be slowing/changing for the better. Mind showing me the source for your statement that C wasn't developed to impact sx?

Hi ZiaSolis,

This could just be semantics. But you couldn't notice a symptom difference because you can't compare what symptoms you haven't experienced as a result of copaxone to what you would have experienced if you had been untreated since you have no idea what symptoms you WOULD have experienced without copaxone or on a different dosing schedule.

So no, you couldn't make the statement that you "saw no difference symptom wise" and attribute that to your dosing regimen unless you could expect to have had an MS attack and therefore new symptoms on a different regimen or none at all.

And since copaxone is only estimated to prevent about 1 attack every 2+ years, I am not sure you can really make any determination on efficacy based on skipping doses, doubling doses, etc. unless you've done this over the long term. And then you'd need to compare it to how you would have done either with nothing, or with regular dosing, or regular double-dosing, etc. That's why there's clinical trials, because with such a variable disease, it's almost impossible to have a reliable pattern of cause/effect for just one person.

I can't offer you evidence that copaxone doesn't affect existing symptoms except that none of the clinical trial data I've read even measured its impact on existing symptoms. So if the trials didn't measure its impact on symptoms, then I assumed that it wasn't developed to impact existing symptoms. The results talk about rates of disease progression and rates to reach certain EDSS points, but they don't talk about improvements in EDSS over and above what they were at the beginning of the trial.

But I agree with you that certainly copaxone is suppose to help prevent new symptoms from occurring. It's just not that good at it so you could still expect to see some disease activity, even if you were dosing at an optimum level. But to determine whether dosing is the cause of no disease activity, or copaxone at all, or just plain disease activity idiosyncracies, I think it would be impossible to attribute anything to one particular cause.