Wolinsky Jerry S
University of Texas Health Science Center at Houston, 6431 Fannin Street, Houston, TX 77030, USA.
Mult Scler. 2004 Jun;10 Suppl 1:S65-71; discussion S71-2. doi: 10.1177/135245850401000112.
The PROMiSe trial is a multinational, multicentre, double-blind, placebo-controlled trial evaluating the effects of glatiramer acetate treatment over 3 years in patients with primary progressive multiple sclerosis (PPMS). A total of 943 patients were enrolled, and all those remaining on-study had completed at least 24 months as of October 2002. Baseline clinical and MRI characteristics and select correlations are reported here. A total of 3.9% of patients exhibited confirmed relapse over 1904 patient-years of exposure, indicating success of efforts to exclude relapsing MS types. Of the 26.3% of patients who have prematurely withdrawn from the study, only 36% discontinued after meeting the study primary endpoint of disease progression. The progression rate in patients in the low Expanded Disability Status Scale (EDSS) stratum (3.0-5.0) observed thus far is markedly lower than the 50% annual progression rate estimate used for determining size and statistical power of the trial; progression was observed in 16.1% of patients with 12 months of study exposure. These early findings raise some concern about the ability of the trial to demonstrate a significant treatment effect, and suggest that the short-term natural history of PPMS may not be as aggressive as previously assumed.
PROMiSe试验是一项跨国、多中心、双盲、安慰剂对照试验，旨在评估醋酸格拉替雷治疗原发性进展型多发性硬化症（PPMS）患者3年的效果。共招募了943名患者，截至2002年10月，所有仍在研究中的患者均已完成至少24个月的研究。本文报告了基线临床和MRI特征以及选定的相关性。在1904患者年的暴露时间里，共有3.9%的患者出现确诊复发，这表明排除复发型多发性硬化症类型的努力取得了成功。在提前退出研究的26.3%的患者中，只有36%在达到疾病进展的主要研究终点后停药。到目前为止，在低扩展残疾状态量表（EDSS）分层（3.0 - 5.0）患者中观察到的进展率明显低于用于确定试验规模和统计效力的50%的年进展率估计值；在接受12个月研究暴露的患者中，有16.1%观察到病情进展。这些早期发现引发了对该试验证明显著治疗效果能力的一些担忧，并表明PPMS的短期自然病程可能不像之前假设的那样具有侵袭性。
