Glatiramer Acetate Effects on MRI and Disease Activity in MS
Abstracts & Commentary
Sources: Comi G, et al. European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging-measured disease activity and burden in patients with re-lapsing multiple sclerosis. Ann Neurol. 2001;49:290-297; Filippi M, et al. Glatiramer acetate reduces the proportion of new multiple sclerosis lesions evolving into "black holes." J Neurol. 2001;248(suppl 2):112; Rovaris M, et al. Effect of glatiramer acetate on brain volume in patients with relapsing-remitting multiple sclerosis. J Neurol. 2001;248(suppl 2):27.
In this controlled multicenter study, 239 patients with relapsing MS (including patients with 1 or more relapses in the past 2 years, and 1 enhancing lesion on screening MRI) were randomized to either a glatiramer acetate (GA) treated group, or a placebo group. Patients underwent monthly MRIs and clinical assessments over 9 months. Treatment with GA caused a significant reduction in the total number of enhancing lesions compared with placebo (-10.8, P = .003), approximately a 29% reduction, as well as a number of new enhancing lesions (P < .003), monthly change in volume of enhancing lesions (P = .01), change in volume (P = .006), and a number of new lesions seen on T2-weighted images (P < .003). There was a decrease in relapse rate of 33% in GA-treated patients (P = .012), with 0.51 relapses/subject, vs. 0.76 relapses/subject in the control group. Steroid treatments were required in 33.6% of GA patients vs. 39.2% of patients in the placebo arm. All effects increased slowly over time, with significant separation from the control group after 6 months. As expected for the short study period, there were no significant differences in the disability scores between the 2 groups.
Additional MRI data from the same clinical trial presented last month at the European Neurological Society Meeting in Paris showed that while GA appeared to reduce the number of "black holes" being formed on T1 brain MRI, it did not seem to reduce the process of brain atrophy compared to placebo controls in the 9-month study period.
Commentary
Several large clinical trials have been published on the treatment of relapsing forms of MS with different preparations of interferon-beta, documenting consistent benefits for attack frequency, and highly significant reductions in disease activity on brain MRI that could occur within 3 months of drug treatment. It is helpful to have this large series of patients in this controlled clinical trial of GA by Comi and colleagues for comparison. In the study design, changes in disease activity on brain MRI were primary and secondary outcome measures, while relapse rate and other clinical measures were actually tertiary. The study was appropriately powered to demonstrate a benefit within a 9-month period, although effects of a longer treatment period would have been of interest given the long-term nature of such drug therapies. As discussed by Comi et al, the relatively delayed MRI effects of GA may reflect the mechanism of action, whereby induction of regulatory T cells are required to migrate to sites of inflammation in the brain. Interferon-beta, in contrast, may more directly inhibit proliferation and migration of lymphocytes into the central nervous system. Nonetheless, this current study reinforces the MRI and clinical benefits of GA in relapsing MS that had previously been presented in smaller numbers of patients. —Brian R. Apatoff
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