results from the 15-year analysis of the US prospective open-label study of glatiramer acetate

[doublevision1]

The ongoing US Glatiramer Acetate (GA) Trial is the longest evaluation of continuous immunomodulatory therapy in relapsing–remitting multiple sclerosis (RRMS). The objective of this study was to evaluate up to 15 years of GA as a sole disease-modifying therapy.

Two hundred and thirty-two patients received at least one GA dose since study initiation in 1991 (mITT cohort), and 100 (43%, Ongoing cohort) continued as of February 2008. Patients were evaluated every 6 months using the Expanded Disability Status Scale (EDSS).

Mean GA exposures were 8.6 ± 5.2, 4.81 ± 3.69, and 13.6 ± 1.3 years and mean disease durations were 17, 13, and 22 years for mITT, Withdrawn and Ongoing cohorts, respectively. 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  0.5 points); 65% had not transitioned to secondary progressive multiple sclerosis (SPMS); 38%, 18%, and 3% reached EDSS 4, 6, and 8.

For all patients on GA therapy (the mITT cohort), ARRs declined from 1.18 ± 0.82 to 0.43 ± 0.58 per year; 54% had stable/improved EDSS scores; 75% had not transitioned to SPMS; 39%, 23%, and 5% reached EDSS 4, 6, and 8.

In conclusion, multiple sclerosis patients with mean disease duration of 22 years administering GA for up to 15 years had reduced relapse rates, and decreased disability progression and transition to SPMS. There were no long-term safety issues.

[shoshin]

That's interesting, but it's hard for me to parse out exactly what it means. It doesn't seem to be a whole lot to go on if the 100 remaining participants were almost half the trial. I get the impression that it's hard for these ongoing studies to compensate for their open label state and also for the differences between those who stay on the drug, those who stop, and those who are lost to follow up. How much difference is there really?

It seems like the more I read, the less I know when to believe any studies. I've even seen arguments that the studies that looked at the CRABs in PPMS were too underpowered to prove that they didn't work, although that seems to have become conventional wisdom.

Of course, it doesn't help that they don't know the extent that the things they can measure relatively easily (lesions on MRI, enhancing lesions, relapses) correlated with the things they want to measure (accumulation of damage and disability). It's also hard to measure disability because it tends to accumulate so slowly (at least from a point that can be reliably measured by outsider), it isn't a linear process, and it happens on many fronts in various ways in different people. I saw where at least one early PPMS trial was messed up by the fact that the placebo arm progressed too slowly for the researchers to make an accurate assessment of anything.

Quix posted something somewhere referring to a commentary by Charles Poser on the effectiveness (or lack thereof) of the DMDs (http://content.karger.com/produktedb/produkte.asp?typ=pdf&file=000151525). I really loved the quote from George Schumacher that he ended with: "When somebody finds an effective treatment for MS, you’ll know it without the need for sophisticated statistical calculations."

Sorry, I guess I went off on a tangent from where you started.

sho

[HVAC]

First of  all we have to realize this is Teva's study of the most profitable drug it has ever made. Thanks to Copaxone Teva boasts a cash flow of a billion dollars.

Now if GA is so safe and affective if we could only get Novartis's Capaxone, (GA) in the U.S.. Teva is still fighting it the courts as of this month. Then we could have some competition. Teva goes around getting sued by every drug maker for breaking there patents with generics and pays the drug makers to settle.