June 8, 2004
Source: Teva Neuroscience, Inc.
Doctor's Guide Publishing Limited
According to new data published in the April 27 edition of Neurology, Copaxone® (glatiramer acetate injection) significantly reduces brain atrophy in patients living with relapsing-remitting multiple sclerosis (RRMS). As brain atrophy is a sensitive measure of the neurodegenerative component of MS, there is an increasing interest in measuring this phenomenon on more accurate and sensitive MRI techniques.
The study utilized a post-hoc analysis of a fully automated, normalized technique for analyzing MRI scans. The technique, known as SIENA (structural image evaluation of normalized atrophy), reduces measurement error and increases the power to detect small but significant changes in brain volume by more than twofold compared to older techniques. There is continued interest in developing measurements, such as SIENA, to further assess brain atrophy.
The study included 207 RRMS patients randomized to Copaxone (n=102) or placebo (n=105) for a period of nine months, followed by a second open-label period of an additional nine months where all patients took Copaxone (n=194). In 13 patients, data loss was due to inadequate image quality for a reliable application of SIENA.
The reduction in brain volume expressed as percent brain volume change (PBVC) throughout the 18-month study was observed when comparing patients originally randomized to Copaxone and those originally randomized to placebo. During the initial double-blind phase, PBVC was slightly, but not significantly less in patients treated with Copaxone.
In the second period, between nine and 18 months, PBVC was significantly lower in Copaxone (glatiramer acetate injection) patients compared to those originally randomized to placebo (-0.6% vs. -1.0%, p=0.015). Moreover, for the whole 18 month period, PBVC was significantly less in patients originally randomized to Copaxone (- 1.5% vs. -2.0%, p= 0.037).
The results of this study reaffirm two previous studies. In the first study, a subcohort from the United States pivotal study with Copaxone, placebo patients (n=13) exhibited a nearly threefold greater annual decline (p=0.0078) in brain volume after 24 months than the Copaxone treated patients (n=14) (1). The second study was the open label, long-term follow up to the placebo-controlled pivotal US trial of Copaxone. Those patients originally randomized to Copaxone (n=69) had 6.7 years of exposure to therapy and showed less brain atrophy than those originally randomized to placebo (n=66) (p=0.041) and only on active treatment for 4.0 years (2). Thus, Copaxone has shown an effect on brain atrophy in both short term trials and long term follow up.
Dr. Jerry S. Wolinsky, Bartels Family Professor of Neurology, The University of Texas Health Science Center at Houston, commented on the study findings. "Results from this study support an effect of glatiramer acetate on limiting brain atrophy. Evolving MRI analytic techniques are improving our ability to reliably detect brain volume change and the neurodegenerative components of the pathology of MS and to study an impact of treatment on this process." In the current study, both SIENA and an older semi-automated, non- normalized technique were used to assess brain volume from MRI images in study patients. Mean values for PBVC were similar using both techniques, but statistically significant reduction in brain atrophy with Copaxone was observed with the more sensitive and accurate SIENA method, but not with the old technique. "Using a technique with less measurement error and improved statistical power not only increases our confidence in study outcomes, but decreases the number of patients required in future studies," said Dr Wolinsky. "We also need to be aware of variances between measurement techniques in previous studies when comparing the effects of different MS therapies on slowing neurodegeneration."
Copaxone (glatiramer acetate injection) is indicated for the reduction of the frequency of relapses in relapsing-remitting MS. The most common side effects of Copaxone are redness, pain, swelling, itching, or a lump at the site of injection, weakness, infection, pain, nausea, joint pain, anxiety, and muscle stiffness. Copaxone is now approved in 42 countries worldwide, including the United States, Canada, Australia, Israel, and all European countries. In Europe, Copaxone is marketed by Teva Pharmaceutical Industries Ltd. and Aventis Pharma. In North America, Copaxone is marketed by Teva Neuroscience Inc.
Copaxone is a registered trademark of Teva Pharmaceutical Industries Ltd.
(1) Ge, Y. et. al. Glatiramer Acetate (Copaxone) Treatment in Relapsing-Remitting Multiple Sclerosis. Neurology, 2000, 54:813-817.
(2) Wolinsky, JS. et. al. United States Open-Label Glatiramer Acetate
Extension Trial for Relapsing Multiple Sclerosis: MRI and Clinical Correlates.
Multiple Sclerosis, 2001, 7:33-41 [JSW1].
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