Therapy - immunomodulation - Part IThursday, September 29, 2005, 15:30 - 17:00
Long-term follow-up of patients treated with glatiramer acetate: a multi-centre, multi-national extension of the European/Canadian double-blind, placebo-controlled, MRI-monitored trialM. Rovaris, G. Comi, M.A. Rocca, D. Ladkani, P. Valsasina, E. Pieri, G. Shifroni, J.S. Wolinsky, M. Filippi (Milan, I; Petah Tiqva, IL; Netanya, IL; Houston, USA)
Background: Glatiramer acetate (GA) is effective in reducing clinical and MRI activity in relapsing-remitting (RR) MS. Serial MRI data on a long-term basis were never obtained for large samples of GA-treated patients.
Goals: To investigate the long-term evolution of clinical and MRI findings in patients with RRMS who participated into the GA 9003 trial, in order to explore the correlates of long-term GA treatment.
Methods: The 9003 study consisted of two consecutive phases, each lasting nine months. The first treatment phase was randomized, double-blind and placebo-controlled. The second was an open-label, active treatment phase for all patients. Treatment consisted of daily administration of 20 mg GA subcutaneously. All patients underwent brain MRI at screening (to be included, they had to have one or more enhancing lesions), baseline, every month during the double-blind phase and every three months during the open-label phase. Clinical assessment included neurological visits with Expanded Disability Status Scale (EDSS) score rating. For the long-term follow-up (LTFU), dual echo, pre- and post-gadolinium T1-weighted brain MRI scans were obtained with the same acquisition scheme as for the original trial and a neurological assessment was performed. Total T2-hyperintense and T1-hypointense lesion volumes, as well as normalized brain volumes (NBV) and percentage BV changes (PBVC), were measured.
Results: One hundred and forty-two of 224 patients who completed the 9003 study (63.4%) underwent the LTFU after a mean period of 5.8 years. Seventy-three of them had been treated with GA since the study initiation. At 9003 baseline, there were no significant differences between patients who subsequently came at LTFU and those who did not. Among the former ones, MRI measures of disease burden and activity, as well as brain volume changes, at LTFU did not significantly differ between patients originally assigned to placebo and those who were always treated with GA. The proportion of patients who did not reach relevant locomotor disability (EDSS >= 6.0) at LTFU was significantly greater in patients treated with GA during the first nine months of the 9003 trial (p = 0.03). PBVC at LTFU was significantly correlated with T2 lesion volume at study entry.
Conclusions: This study indicates that the earlier initiation of GA treatment in patients with active RRMS might have a favorable impact on the long-term disease evolution.