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醋酸格拉替雷与β-干扰素制剂在复发缓解型多发性硬化症中的疗效比较

Comparative effectiveness of glatiramer acetate and interferon beta formulations in relapsing-remitting multiple sclerosis.

作者信息

Kalincik Tomas, Jokubaitis Vilija, Izquierdo Guillermo, Duquette Pierre, Girard Marc, Grammond Pierre, Lugaresi Alessandra, Oreja-Guevara Celia, Bergamaschi Roberto, Hupperts Raymond, Grand'Maison Francois, Pucci Eugenio, Van Pesch Vincent, Boz Cavit, Iuliano Gerardo, Fernandez-Bolanos Ricardo, Flechter Shlomo, Spitaleri Daniele, Cristiano Edgardo, Verheul Freek, Lechner-Scott Jeannette, Amato Maria Pia, Cabrera-Gomez Jose Antonio, Saladino Maria Laura, Slee Mark, Moore Fraser, Gray Orla, Paine Mark, Barnett Michael, Havrdova Eva, Horakova Dana, Spelman Timothy, Trojano Maria, Butzkueven Helmut

机构信息

Department of Medicine, University of Melbourne, Melbourne, Australia and Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia

Department of Medicine, University of Melbourne, Melbourne, Australia and Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia.

出版信息

Mult Scler. 2015 Aug;21(9):1159-71. doi: 10.1177/1352458514559865. Epub 2014 Dec 5.

Abstract

BACKGROUND

The results of head-to-head comparisons of injectable immunomodulators (interferon β, glatiramer acetate) have been inconclusive and a comprehensive analysis of their effectiveness is needed.

OBJECTIVE

We aimed to compare, in a real-world setting, relapse and disability outcomes among patients with multiple sclerosis (MS) treated with injectable immunomodulators.

METHODS

Pairwise analysis of the international MSBase registry data was conducted using propensity-score matching. The four injectable immunomodulators were compared in six head-to-head analyses of relapse and disability outcomes using paired mixed models or frailty proportional hazards models adjusted for magnetic resonance imaging variables. Sensitivity and power analyses were conducted.

RESULTS

Of the 3326 included patients, 345-1199 patients per therapy were matched (median pairwise-censored follow-up was 3.7 years). Propensity matching eliminated >95% of the identified indication bias. Slightly lower relapse incidence was found among patients treated with glatiramer acetate or subcutaneous interferon β-1a relative to intramuscular interferon β-1a and interferon β-1b (p≤0.001). No differences in 12-month confirmed progression of disability were observed.

CONCLUSION

Small but statistically significant differences in relapse outcomes exist among the injectable immunomodulators. MSBase is sufficiently powered to identify these differences and reflects practice in tertiary MS centres. While the present study controlled indication, selection and attrition bias, centre-dependent variance in data quality was likely.

摘要

背景

注射用免疫调节剂(干扰素β、醋酸格拉替雷)的直接比较结果尚无定论,需要对其有效性进行全面分析。

目的

我们旨在比较在实际临床环境中,接受注射用免疫调节剂治疗的多发性硬化症(MS)患者的复发率和残疾情况。

方法

使用倾向得分匹配法对国际MSBase注册数据进行成对分析。在六项关于复发率和残疾情况的直接比较分析中,使用配对混合模型或针对磁共振成像变量进行调整的脆弱比例风险模型,对四种注射用免疫调节剂进行比较。进行了敏感性和效能分析。

结果

在纳入的3326例患者中,每种治疗方法匹配了345 - 1199例患者(成对删失随访的中位数为3.7年)。倾向得分匹配消除了>95%已识别的指征偏倚。相对于肌肉注射干扰素β-1a和干扰素β-1b,接受醋酸格拉替雷或皮下注射干扰素β-1a治疗的患者复发率略低(p≤0.001)。在12个月确诊的残疾进展方面未观察到差异。

结论

注射用免疫调节剂在复发率方面存在微小但具有统计学意义的差异。MSBase有足够的效能识别这些差异,并反映了三级MS中心的实际情况。虽然本研究控制了指征、选择和失访偏倚,但数据质量可能存在中心依赖性差异。

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