醋酸格拉替雷治疗复发缓解型和临床孤立综合征多发性硬化的获益-风险分析。

Benefit-risk analysis of glatiramer acetate for relapsing-remitting and clinically isolated syndrome multiple sclerosis.

机构信息

OXON Epidemiology, Paseo de la Habana 169, Madrid, Spain.

出版信息

Clin Ther. 2012 Jan;34(1):159-176.e5. doi: 10.1016/j.clinthera.2011.12.006.

DOI:10.1016/j.clinthera.2011.12.006

PMID:22284996

Abstract

BACKGROUND

Glatiramer acetate (GA) and interferon beta-1 are licensed for treating patients with multiple sclerosis (MS). However, they have slightly different indications, side effect profiles, and tolerability.

OBJECTIVE

The purpose of this study was to assess the benefit-risk (BR) profile of GA in relapse-remitting MS (RRMS) and clinical isolated syndrome (CIS).

METHODS

MEDLINE, EMBASE, and the Cochrane Register were searched for randomized controlled trials and comparative observational cohort studies in patients older than 18 years who were treated with 20 mg daily of subcutaneous GA for RRMS or CIS. Uncommon risks of GA were assessed in the World Health Organization (WHO) global spontaneous adverse reaction (AR) reports database (Vigibase).

RESULTS

A total of 248 potentially relevant articles were identified by the search; of these, 11 studies were included in the review: 7 trials and 4 cohort studies with a total of 4759 patients. The proportion of studies included from the search was 4.4% of all titles, 9.3% of all reviewed abstracts, and 45.8% of all eligible articles for review. In patients with RRMS relapse-free rates were higher with GA than with placebo (relative risk [RR] = 1.35; 95% CI, 0.99-1.84) and similar to interferons (IFNs) (RR = 0.99; 95% CI, 0.93-1.06). There was a 33% reduction in clinical progression (RR = 0.69; 95% CI, 0.42-1.13) for GA compared with placebo and an 18% reduction (RR = 0.82; 95% CI, 0.68-0.98) compared with IFNs. Study discontinuations because of adverse events were similar for GA and IFNs (RR = 0.89; 95% CI, 0.57-1.41). In Vigibase, 1271 cases were identified with a suspected relation to GA. Several ARs were identified as statistically strong signals of disproportionate reporting for GA compared with IFNs. WHO critical ARs combined were similar between GA and IFNs, with a reporting rate of 69 per 100,000 person-years for GA. The relative net BR difference was 10.2% in favor of GA compared with placebo and 6.4% compared with IFNs.

CONCLUSIONS

GA reduced relapses and clinical progression compared with placebo or standard treatment and clinical progression compared with IFNs. Serious adverse events were comparable in GA and IFNs. The BR assessments that were based on these data found that the clinical benefits of GA outweigh the risks, although results differ, depending on the quantitative BR model used, and are limited by the absence of reliable data for assigning weights to the model.

摘要

背景

醋酸格拉替雷和干扰素β-1 已被批准用于治疗多发性硬化症（MS）患者。然而，它们在适应证、副作用谱和耐受性方面略有不同。

目的

本研究旨在评估醋酸格拉替雷在复发缓解型多发性硬化症（RRMS）和临床孤立综合征（CIS）中的获益-风险（BR）状况。

方法

检索 MEDLINE、EMBASE 和 Cochrane 注册中心，纳入 20 毫克每日皮下注射用于治疗 RRMS 或 CIS 的年龄大于 18 岁患者的随机对照试验和比较性观察队列研究。通过世界卫生组织（WHO）全球自发不良反应（AR）报告数据库（Vigibase）评估醋酸格拉替雷的罕见风险。

结果

通过检索共确定了 248 篇潜在相关文章，其中 11 项研究被纳入综述：7 项试验和 4 项队列研究，共纳入 4759 例患者。从检索中纳入研究的比例分别为所有标题的 4.4%、所有综述摘要的 9.3%和所有符合条件的综述文章的 45.8%。在 RRMS 患者中，与安慰剂相比，醋酸格拉替雷的无复发率更高（相对风险 [RR] = 1.35；95%置信区间，0.99-1.84），与干扰素相似（RR = 0.99；95%置信区间，0.93-1.06）。与安慰剂相比，醋酸格拉替雷可使临床进展减少 33%（RR = 0.69；95%置信区间，0.42-1.13），与干扰素相比减少 18%（RR = 0.82；95%置信区间，0.68-0.98）。由于不良反应而停药的情况，醋酸格拉替雷与干扰素相似（RR = 0.89；95%置信区间，0.57-1.41）。在 Vigibase 中，共发现与醋酸格拉替雷疑似相关的 1271 例病例。与干扰素相比，一些不良反应被确定为与醋酸格拉替雷不成比例报告的统计学强信号。醋酸格拉替雷和干扰素的 WHO 关键不良反应发生率相似，为每 100000 人年 69 例。与安慰剂相比，GA 的相对净 BR 差异为 10.2%，与 IFNs 相比为 6.4%。