Effect of glatiramer acetate and implications
http://brain.oupjournals.org/cgi/content/abstract/124/9/1803
Brain, Vol. 124, No. 9, 1803-1812,
September 2001
Marco Rovaris1, Giancarlo Comi2,
Maria A. Rocca1, Jerry S. Wolinsky3, Massimo Filippi1 and and the The European/Canadian
Glatiramer Acetate Study Group,*
1 Neuroimaging Research Unit and
2 Clinical Trials Unit, Department of Neuroscience, Scientific Institute
and University Ospedale San Raffaele, Milan, Italy, 3 The University of
Texas–Houston, Health Science Center, Houston, Texas
Correspondence to: Massimo Filippi,
Department of Neuroscience, Scientific Institute Ospedale San Raffaele,
via Olgettina 60, 20132 Milan, Italy E-mail: filippi.massimo@hsr.it
The assessment of brain volume change
with serial MRI provides an objective measure of an important component
of the pathology of multiple sclerosis.
Glatiramer acetate (GA) has a beneficial
effect on clinical and MRI measures of disease activity and burden in patients
with relapsing–remitting (RR) multiple sclerosis.
This study investigated the impact
of GA treatment on the development of brain atrophy in RR multiple sclerosis
patients.
The study consisted of a 9-month,
double-blind, placebo-controlled phase followed by a 9-month open-label
phase. Patients were randomized to receive either 20 mg GA or placebo by
daily subcutaneous injections and underwent brain MRI scans every month
during the first phase, and every 3 months during the second phase of the
study.
Using a semi-automated segmentation
technique based on local thresholding, brain volume was measured from seven
contiguous periventricular slices from the scans obtained at baseline,
the end of the double-blind phase and the end of the study.
From the original trial cohort, image
sets from 113 out of 119 patients randomized to GA, and 114 out of 120
randomized to placebo treatment were evaluated. Brain volume was significantly
correlated with patients' disability at each time-point.
No significant differences between
placebo- and GA-treated patients were found for baseline brain volume and
rate of brain volume change over the study, even though a possible late
trend for treatment with GA to retard the loss of brain volume was observed.
There was a significant, but modest,
correlation between MRI activity during the double-blind phase, and brain
volume change over the entire study among patients originally treated with
placebo.
The modest correlation between enhancement
frequency and brain atrophy loss indicates that the suppression of inflammatory
activity in RR multiple sclerosis patients is not fully and rapidly associated
with a similar effect on the global neurodegenerative processes.
This study also suggests that any
effect of GA in preventing brain volume decrease is not evident early following
institution of treatment.
Copyright © 2001 Oxford University
Press.