Achiron Anat, Fredrikson Sten
Multiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer, and Sackler School of Medicine, Tel-Aviv University, Israel.
J Neurol Sci. 2009 Feb 1;277 Suppl 1:S19-24. doi: 10.1016/S0022-510X(09)70007-3.
For over a decade, four immunomodulatory therapies have been available for the treatment of relapsing remitting multiple sclerosis. However, few direct comparative data were available to facilitate the choice of treatment. This choice has been influenced by the perception that interferon-beta preparations have greater efficacy than glatiramer acetate, due to apparently more rapid and robust reduction of gadolinium-enhancing lesions seen on magnetic resonance imaging in the pivotal trials of these agents. This situation has changed in the last year, with the outcomes of three randomised clinical trials comparing the efficacy and safety of glatiramer acetate with that of a high-dose interferon-beta in relapsing remitting multiple sclerosis. These are the REGARD, BEYOND and BECOME trials. In the REGARD trial, 764 patients were randomised to treatment with either interferon-beta 1a sc 44 microg or glatiramer acetate for 96 weeks; no significant difference in the time to first relapse was observed. The largest of the three comparative studies, the BEYOND trial, compared treatment with interferon-beta 1b sc 500 microg, interferon-beta 1b sc 250 microg or glatiramer acetate for two years in 2,244 patients. The hazard ratio for multiple relapses was close to unity for comparisons between all groups, indicating equivalent efficacy in all three treatment arms. Relapse rates (around 0.3 relapses/year) in all these studies were much lower than anticipated and lower than those reported a decade previously in the pivotal trials of beta-interferons and glatiramer acetate. No unexpected safety issues were identified in any of these studies. The completion of these direct comparative studies has considerably enriched the clinical evidence database by contributing large numbers of patients. This provides an invaluable contribution for helping the physician make an informed choice about treatment. The results of the direct comparative studies provide evidence that glatiramer acetate and high-dose interferon-beta preparations have comparable clinical efficacy.
十多年来，有四种免疫调节疗法可用于治疗复发缓解型多发性硬化症。然而，几乎没有直接的对比数据来帮助选择治疗方法。由于在这些药物的关键试验中，磁共振成像显示钆增强病变的减少明显更快、更显著，人们认为β-干扰素制剂比醋酸格拉替雷更有效，这一观念影响了治疗选择。去年情况发生了变化，三项随机临床试验比较了醋酸格拉替雷与高剂量β-干扰素在复发缓解型多发性硬化症中的疗效和安全性。这些试验分别是REGARD试验、BEYOND试验和BECOME试验。在REGARD试验中，764名患者被随机分配接受皮下注射44微克的β-干扰素1a或醋酸格拉替雷治疗96周；首次复发时间没有显著差异。三项比较研究中规模最大的BEYOND试验，在2244名患者中比较了皮下注射500微克的β-干扰素1b、皮下注射250微克的β-干扰素1b或醋酸格拉替雷治疗两年的效果。所有组之间多次复发的风险比接近1，表明三个治疗组的疗效相当。所有这些研究中的复发率（约每年0.3次复发）远低于预期，也低于十年前β-干扰素和醋酸格拉替雷关键试验中报告的复发率。在任何一项研究中都未发现意外的安全问题。这些直接对比研究的完成，通过纳入大量患者，极大地丰富了临床证据数据库。这为帮助医生做出明智的治疗选择提供了宝贵的贡献。直接对比研究的结果提供了证据，表明醋酸格拉替雷和高剂量β-干扰素制剂具有相当的临床疗效。
