Long-term follow-up of patients treated with glatiramer acetate: a multicentre, multinational extension of the European/Canadian double-blind, placebo-controlled, MRI-monitored trial

Abstract

Glatiramer acetate (GA) is effective in reducing clinical and magnetic resonance imaging (MRI) activity in relapsing-remitting multiple sclerosis (RRMS). Serial long-term MRI data are lacking for large cohorts of GA-treated patients. The European/Canadian GA 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 with daily administration of 20 mg GA subcutaneously for all patients. For the long-term follow-up (LTFU), dual echo, pre- and postgadolinium T1-weighted brain MRI scans were obtained with the same acquisition scheme as for the original trial and a neurological assessment was performed. Lesion volumes, normalized brain volumes and percentage brain volume changes (PBVC) were measured. One hundred and forty-two (63.4%) of the 224 patients who completed the two phases of the European/Canadian study underwent the LTFU after a mean period of 5.8 years (range: 5.3-6.4); 73 were treated with GA from study initiation. MRI measures at LTFU did not significantly differ between patients originally assigned to placebo and those who were always treated with GA, but the proportion of patients who did not require walking aids at LTFU was lower in the latter group (P=0.034). PBVC between baseline and LTFU was significantly correlated with lesion load at study entry. An earlier initiation of GA treatment in patients with active RRMS might, at least partially, have a favourable impact on long-term disease evolution.

Effects of early treatment with glatiramer acetate in patients with clinically isolated syndrome

“…11 Long-term (mean 5.8 years) follow-up of patients in the European/Canadian study showed that patients who received early treatment with GA were significantly (p = 0.034) less likely to require a walking aid than patients who received GA after a delay of only nine months. 18 Additionally, results of a small proton MR spectroscopy study during the double-blind treatment phase in a subset of patients in PreCISe suggest axonal protection by GA. 19 Despite significant improvements with early versus delayed GA treatment on multiple MRI measures, including brain atrophy, no significant difference between the GA early-and delayed-treatment groups was observed in the rate of confirmed progression of disability, which was reported for only 21% of patients in each group over the five-year study. This may be due in part to the low rate of progression during early MS, but may also reflect the study design, in which patients in the delayed-treatment group received GA immediately upon conversion to CDMS.…”

The heritage of glatiramer acetate and its use in multiple sclerosis

“…Long-term and real-word data Even with all the limitations of long-term extension studies, due to potential selection bias, available data suggest that the efficacy of GA is maintained over time [63][64][65][66][67][68][69][70][71]. Moreover, there have been no reports of rebound effect or delayed disease reactivation after treatment discontinuation in extensions of clinical trials or postmarketing studies [63,70,72,73].…”

“…Moreover, there have been no reports of rebound effect or delayed disease reactivation after treatment discontinuation in extensions of clinical trials or postmarketing studies [63,70,72,73].…”

“…Very long-term use of GA appears to be associated with stable disease activity (cumulative ARR = 0.2; 24.3 % of patients remained free of relapse for the entire period) and low levels of accumulated disability (mean EDSS score 3.1 vs. 2.4 at baseline). The extension of the European/Canadian MRI study offers serial long-term MRI data for a large cohort of patients treated with GA [70]. After the 9-month doubleblind, placebo-controlled phase, all patients entered an open-label, active treatment phase in which they received GA 20 mg/mL once daily for a further 9 months, with a long-term follow-up visit (LTFU) scheduled at least five years after study entry.…”

A place of first-line drugs in treatment of multiple sclerosis

“…Продолжен-ное наблюдение за пациентами в открытой фазе данного исследования (94% от изначального числа) установило снижение количества очагов на Т2-взвешенных изобра-жениях в группе с отсроченным началом терапии на 54% и дальнейшее снижение на 24,6% в группе раннего начала терапии [54]. Наблюдение в течение 5 лет за обеими груп-пами не выявило значимых различий в МРТ-картине, од-нако число пациентов без прогрессирования по шкале EDSS было достоверно больше в первой группе [55]. На основании данных долгосрочных наблюдений можно предположить факт установления иммунологической то-лерантности при длительном использовании ГА в группе пациентов, чувствительных к данной терапии.…”