Filippi Massimo, Wolinsky Jerry S, Comi Giancarlo
Neuroimaging Research Unit, Institute of Experimental Neurology and University Ospedale San Raffaele, Milan, Italy.
Lancet Neurol. 2006 Mar;5(3):213-20. doi: 10.1016/S1474-4422(06)70327-1.
Parenterally administered glatiramer acetate reduces the frequency of relapses and the formation of active brain lesions seen with MRI in multiple sclerosis. This study assessed whether two doses of glatiramer acetate given orally could improve clinical and MRI measures of inflammation and neurodegeneration in a large cohort of patients with relapsing-remitting multiple sclerosis.
1912 patients with relapsing-remitting multiple sclerosis were screened and 1651 were randomised to receive 50 mg or 5 mg of glatiramer acetate or placebo by daily oral administration over 14 months. The intention-to-treat cohort consisted of 1644 patients who took at least one dose of study medication (50 mg glatiramer acetate [n=543], 5 mg glatiramer acetate [n=553], placebo [n=548]). After baseline investigation, clinical assessments were done every 2 months and MRI was obtained for all patients at baseline and at study exit. Additionally, MRI was undertaken every 2 months for a cohort of 486 patients. The primary outcome was the total number of confirmed relapses observed during the study period. Several prespecified clinical and MRI secondary and tertiary outcomes assessed treatment efficacy on inflammation and neurodegeneration due to multiple sclerosis.
The cumulative number of confirmed relapses did not differ between the two active treatment groups and the placebo group. Relative to placebo, the rate ratio for the 50 mg glatiramer acetate treated group was 0.92 (95% CI 0.77-1.08, p=0.30) and for the 5 mg glatiramer acetate treated group was 0.98 (0.83-1.15, p=0.76). No drug effect was seen for any of the secondary and tertiary endpoints. The study drug was safe and well tolerated.
5 mg and 50 mg glatiramer acetate administered orally on a daily basis do not affect relapse rate or other clinical and MRI parameters of disease activity and burden in patients with relapsing-remitting multiple sclerosis. Treatment with oral formulations of glatiramer acetate at the doses tested cannot be recommended.
肠胃外注射醋酸格拉替雷可降低多发性硬化症患者的复发频率，并减少MRI显示的脑部活动性病灶的形成。本研究评估了口服两剂醋酸格拉替雷是否能改善一大群复发缓解型多发性硬化症患者炎症和神经退行性变的临床及MRI指标。
对1912例复发缓解型多发性硬化症患者进行筛查，1651例患者被随机分配，在14个月内每日口服50mg或5mg醋酸格拉替雷或安慰剂。意向性治疗队列由1644例服用至少一剂研究药物的患者组成（50mg醋酸格拉替雷[n = 543]，5mg醋酸格拉替雷[n = 553]，安慰剂[n = 548]）。在基线调查后，每2个月进行一次临床评估，并在基线和研究结束时为所有患者进行MRI检查。此外，对486例患者每2个月进行一次MRI检查。主要结局是研究期间观察到的确诊复发总数。几个预先设定的临床和MRI次要及三级结局评估了治疗对多发性硬化症引起的炎症和神经退行性变的疗效。
两个活性治疗组与安慰剂组之间确诊复发的累积数没有差异。相对于安慰剂，50mg醋酸格拉替雷治疗组的率比为0.92（95%CI 0.77 - 1.08，p = 0.30），5mg醋酸格拉替雷治疗组的率比为0.98（0.83 - 1.15，p = 0.76）。在任何次要和三级终点均未观察到药物效应。研究药物安全且耐受性良好。
每日口服5mg和50mg醋酸格拉替雷不会影响复发缓解型多发性硬化症患者的复发率或疾病活动及负担的其他临床和MRI参数。不推荐使用所测试剂量的醋酸格拉替雷口服制剂进行治疗。
