Brochet B
Service de neurologie, pôle des neurosciences cliniques, clinique de la SEP, CHU Pellegrin, 33076 Bordeaux, France.
Rev Neurol (Paris). 2008 Nov;164(11):917-26. doi: 10.1016/j.neurol.2008.02.045. Epub 2008 May 16.
Multiple sclerosis is a chronic progressive neurological disorder. For this reason, the clinician needs to have access to treatments that are effective and well-tolerated over decades. However, in the absence of long-term controlled clinical trials, it is difficult to assess the long-term benefit provided by currently available immunomodulatory treatments. The objective of this report is to review the strengths and limitations of available long-term data obtained in different phases of the randomized phase III clinical trial with glatiramer acetate collected over a 10-year period in particular.
Data were obtained from six published analyses of data from the phase III randomized clinical trial of glatiramer acetate performed at different times over a 10-year period. Initially patients were randomized to receive glatiramer acetate (n=125) or placebo (n=126) for 24 months under a double blind scheme, which was subsequently extended to up to 35 months. All patients were then proposed to continue glatiramer acetate treatment in an open-label prospective extension. Analyses of this extension study were performed at six and eight years after initial randomization. Finally, a pooled analysis was performed after a mean treatment duration of 10 years of all patients who had ever received glatiramer acetate during the study. Data were available for 68% of the original cohort at 10 years. At this stage, 108 patients (46.6%) had been continually treated with glatiramer acetate for a mean duration of 10 years.
After one year of treatment, the annualized relapse rate decreased by around 50% from 1.18 relapses/year before inclusion to 0.60 relapses/year. Thereafter, relapse rates continued to decline progressively, reaching less than 0.2 relapses/year from the ninth year of treatment onward. For 65% of patients, EDSS disability scores remained stable or improved over the entire treatment period, and 8% had reached a score of 6 on the EDSS scale (inability to walk unaided) after a mean continuous treatment duration of 10 years. With respect to safety, 23 patients (< 10%) needed to stop treatment due to an adverse event over the 10-year follow-up period. The most frequently encountered adverse events were local injection site reactions and systemic immediate postinjection reactions. No specific safety issue associated with long-term treatment was identified.
The information collected from prospective long-term follow-up of patients treated with glatiramer acetate extending out to 10 years provide clear evidence for the long-term efficacy and adequate safety of this immunomodulatory treatment in the treatment of relapsing-remitting multiple sclerosis over a period of at least 10 years.
多发性硬化症是一种慢性进行性神经疾病。因此，临床医生需要有能在数十年间有效且耐受性良好的治疗方法。然而，由于缺乏长期对照临床试验，很难评估现有免疫调节治疗的长期益处。本报告的目的是回顾尤其是在10年期间收集的醋酸格拉替雷随机III期临床试验不同阶段获得的可用长期数据的优势和局限性。
数据来自于对醋酸格拉替雷III期随机临床试验在10年期间不同时间进行的6次已发表的数据分析。最初，患者在双盲方案下被随机分配接受醋酸格拉替雷（n = 125）或安慰剂（n = 126）治疗24个月，随后延长至35个月。然后所有患者被建议在开放标签的前瞻性延长期继续接受醋酸格拉替雷治疗。在初始随机分组后的6年和8年对该延长期研究进行分析。最后，对研究期间所有接受过醋酸格拉替雷治疗的患者在平均治疗持续10年后进行汇总分析。10年后，原始队列中68%的数据可用。在此阶段，108名患者（46.6%）持续接受醋酸格拉替雷治疗，平均持续时间为10年。
治疗一年后，年化复发率从入组前的每年1.18次复发下降了约50%，至每年0.60次复发。此后，复发率继续逐渐下降，从治疗第九年起降至每年少于0.2次复发。65%的患者在整个治疗期间扩展残疾状态量表（EDSS）残疾评分保持稳定或改善，8%的患者在平均持续治疗10年后EDSS量表达到6分（无法独立行走）。在安全性方面，在10年随访期内，23名患者（<10%）因不良事件需要停止治疗。最常遇到的不良事件是局部注射部位反应和注射后即刻全身反应。未发现与长期治疗相关的特定安全问题。
对接受醋酸格拉替雷治疗的患者进行长达10年的前瞻性长期随访收集的信息，为这种免疫调节治疗在治疗复发缓解型多发性硬化症至少10年期间的长期疗效和充分安全性提供了明确证据。
