复发缓解型多发性硬化症中250微克或500微克β-1b干扰素与20毫克醋酸格拉替雷的对比：一项前瞻性、随机、多中心研究
250 microg or 500 microg interferon beta-1b versus 20 mg glatiramer acetate in relapsing-remitting multiple sclerosis: a prospective, randomised, multicentre study.
作者信息
O'Connor Paul, Filippi Massimo, Arnason Barry, Comi Giancarlo, Cook Stuart, Goodin Douglas, Hartung Hans-Peter, Jeffery Douglas, Kappos Ludwig, Boateng Francis, Filippov Vitali, Groth Maria, Knappertz Volker, Kraus Christian, Sandbrink Rupert, Pohl Christoph, Bogumil Timon, O'Connor P, Filippi M, Arnason B, Cook S, Goodin D, Hartung H-P, Kappos L, Jeffery D, Comi G
机构信息
St Michael's Hospital, Toronto, Canada.
出版信息
Lancet Neurol. 2009 Oct;8(10):889-97. doi: 10.1016/S1474-4422(09)70226-1. Epub 2009 Sep 2.
BACKGROUND
The aim of the Betaferon Efficacy Yielding Outcomes of a New Dose (BEYOND) trial was to compare the efficacy, safety, and tolerability of 250 microg or 500 microg interferon beta-1b with glatiramer acetate for treating relapsing-remitting multiple sclerosis.
METHODS
Between November, 2003, and June, 2005, 2447 patients with relapsing-remitting multiple sclerosis were screened and 2244 patients were enrolled in this prospective, multicentre, randomised trial. Patients were randomly assigned 2:2:1 by block randomisation with regional stratification to receive one of two doses of interferon beta-1b (250 microg or 500 microg) subcutaneously every other day or 20 mg glatiramer acetate subcutaneously every day. The primary outcome was relapse risk, defined as new or recurrent neurological symptoms separated by at least 30 days from the preceding event and that lasted at least 24 h. Secondary outcomes were progression on the expanded disability status scale (EDSS) and change in T1-hypointense lesion volume. Clinical outcomes were assessed quarterly for 2.0-3.5 years; MRI was done at screening and annually thereafter. Analysis was by per protocol. This study is registered, number NCT00099502.
FINDINGS
We found no differences in relapse risk, EDSS progression, T1-hypointense lesion volume, or normalised brain volume among treatment groups. Flu-like symptoms were more common in patients treated with interferon beta-1b (p<0.0001), whereas injection-site reactions were more common in patients treated with glatiramer acetate (p=0.0005). Patient attrition rates were 17% (153 of 888) on 250 microg interferon beta-1b, 26% (227 of 887) on 500 microg interferon beta-1b, and 21% (93 of 445) for glatiramer acetate.
INTERPRETATION
500 microg interferon beta-1b was not more effective than the standard 250 microg dose, and both doses had similar clinical effects to glatiramer acetate. Although interferon beta-1b and glatiramer acetate had different adverse event profiles, the overall tolerability to both drugs was similar.
FUNDING
Bayer HealthCare Pharmaceuticals.
背景
新剂量倍泰龙疗效及产出试验（BEYOND）的目的是比较250微克或500微克β-1b干扰素与醋酸格拉替雷治疗复发缓解型多发性硬化症的疗效、安全性和耐受性。
方法
2003年11月至2005年6月期间，对2447例复发缓解型多发性硬化症患者进行了筛查，2244例患者纳入了这项前瞻性、多中心、随机试验。患者按2:2:1通过区组随机化和区域分层随机分配，分别接受两种剂量的β-1b干扰素（250微克或500微克）皮下隔日注射或20毫克醋酸格拉替雷皮下每日注射。主要结局为复发风险，定义为新出现或复发的神经症状，与前次事件间隔至少30天且持续至少24小时。次要结局为扩展残疾状态量表（EDSS）进展情况和T1加权低信号病变体积变化。临床结局每季度评估2.0 - 3.5年；筛查时及之后每年进行MRI检查。按方案进行分析。本研究已注册，注册号为NCT00099502。
结果
我们发现各治疗组在复发风险、EDSS进展、T1加权低信号病变体积或正常化脑体积方面无差异。流感样症状在接受β-1b干扰素治疗的患者中更常见（p<0.0001），而注射部位反应在接受醋酸格拉替雷治疗的患者中更常见（p = 0.0005）。250微克β-1b干扰素组的患者脱落率为17%（888例中的153例），500微克β-1b干扰素组为26%（887例中的227例），醋酸格拉替雷组为21%（445例中的93例）。
解读
500微克β-1b干扰素并不比标准的250微克剂量更有效，且两种剂量与醋酸格拉替雷的临床效果相似。虽然β-1b干扰素和醋酸格拉替雷的不良事件谱不同，但两种药物的总体耐受性相似。
资助
拜耳医药保健有限公司。
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