Bensimon G, Lacomblez L, Meininger V
Department of Clinical Pharmacology, Hôpital de la Pitié-Salpêtrière, Paris, France.
N Engl J Med. 1994 Mar 3;330(9):585-91. doi: 10.1056/NEJM199403033300901.
Amyotrophic lateral sclerosis is a progressive motor neuron disease for which there is no adequate treatment. Some research suggests that the excitatory amino acid neurotransmitter glutamate may be involved in the pathogenesis.
To evaluate the efficacy and safety of the antiglutamate agent riluzole, we conducted a prospective, double-blind, placebo-controlled trial in 155 outpatients with amyotrophic lateral sclerosis. The dose of riluzole was 100 mg per day. Randomization was stratified according to the site of disease onset (the bulbar region or the limbs). The primary end points were survival and rates of change in functional status. The main secondary end point was change in muscle strength. Analyses were undertaken after 12 months of treatment and at the end of the placebo-controlled period (median follow-up, 573 days).
After 12 months, 45 of 78 patients (58 percent) in the placebo group were still alive, as compared with 57 of 77 patients (74 percent) in the riluzole group (P = 0.014). For patients with bulbar-onset disease, one-year survival rates were 35 percent (6 of 17) with placebo and 73 percent (11 of 15) with riluzole (P = 0.014), whereas for those with limb-onset disease one-year survival was 64 percent and 74 percent, respectively (P = 0.17). The survival advantage with riluzole was smaller (37 percent [29 of 78] with placebo vs. 49 percent [38 of 77] with riluzole) at the end of the placebo-controlled period, but it remained significant in the overall population (P = 0.046) as well as in the patients with bulbar-onset disease (18 percent [3 of 17] vs. 53 percent [8 of 15], P = 0.013). The deterioration of muscle strength was significantly slower in the riluzole group than in the placebo group (P = 0.028). Adverse reactions to riluzole included asthenia, spasticity, and mild elevations in aminotransferase levels. Twenty-seven patients in the riluzole group withdrew from the study, as compared with 17 in the placebo group.
The antiglutamate agent riluzole appears to slow the progression of amyotrophic lateral sclerosis, and it may improve survival in patients with disease of bulbar onset.
肌萎缩侧索硬化症是一种进行性运动神经元疾病，目前尚无有效的治疗方法。一些研究表明，兴奋性氨基酸神经递质谷氨酸可能参与其发病机制。
为评估抗谷氨酸药物利鲁唑的疗效和安全性，我们对155例肌萎缩侧索硬化症门诊患者进行了一项前瞻性、双盲、安慰剂对照试验。利鲁唑的剂量为每日100毫克。随机分组根据疾病起始部位（延髓区或肢体）进行分层。主要终点为生存率和功能状态变化率。主要次要终点为肌肉力量变化。在治疗12个月后以及安慰剂对照期结束时（中位随访时间为573天）进行分析。
12个月后，安慰剂组78例患者中有45例（58%）仍存活，而利鲁唑组77例患者中有57例（74%）仍存活（P = 0.014）。对于延髓起病的患者，安慰剂组的一年生存率为35%（17例中的6例），利鲁唑组为73%（15例中的11例）（P = 0.014），而对于肢体起病的患者，一年生存率分别为64%和74%（P = 0.17）。在安慰剂对照期结束时，利鲁唑的生存优势较小（安慰剂组为37%[78例中的29例]，利鲁唑组为49%[77例中的38例]），但在总体人群中（P = 0.046）以及延髓起病的患者中（18%[17例中的3例]对53%[15例中的8例]，P = 0.013）仍具有显著意义。利鲁唑组肌肉力量的恶化明显慢于安慰剂组（P = 0.028）。利鲁唑的不良反应包括乏力、痉挛和转氨酶水平轻度升高。利鲁唑组有27例患者退出研究，而安慰剂组有17例。
抗谷氨酸药物利鲁唑似乎可减缓肌萎缩侧索硬化症的进展，并且可能提高延髓起病患者的生存率。
