Placebo-controlled multicentre randomised trial of interferon β-1b in treatment of secondary progressive multiple sclerosis
Placebo-controlled multicentre randomised trial of interferon β-1b in treatment of secondary progressive multiple sclerosis
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DOI：
10.1016/s0140-6736(98)10039-9
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发表时间：
1998-11-07
期刊：
影响因子：
168.9
通讯作者：
Toyka, K
中科院分区：
文献类型：
--
作者：
Kappos, L;Polman, C;Toyka, K
背景：β干扰素仅对多发性硬化症(MS)的复发-缓解期患者有益处。在这项多中心、双掩蔽、随机、安慰剂对照的多中心试验中，扩展残疾状态量表(EDSS)评分3.0-6.5的SP-MS门诊患者每隔一天接受800万IUβ-1b干扰素治疗，或服用安慰剂，为期长达3年。主要结果是确认残疾进展的时间，以EDSS增加1.0分来衡量，持续至少3个月，或如果基线EDSS为6.0或6.5，则增加0.5分，在所有患者参与研究至少2年后，对意向治疗人群的安全性和有效性进行前瞻性计划的中期分析。结果358名SP-MS患者被分配安慰剂，360名患者被分配干扰素β-1b；57名患者(31名安慰剂，26名干扰素β-1b)失去了随访。在确认残疾进展的时间上，服用干扰素β-1b的患者有非常显著的差异(p=0.0008)。在2-3年的研究期间，干扰素β-1b使病情进展延迟9-12个月。确定进展的优势比为0.65(95%可信区间为0.52-0.83)。这种有益的效果在叠加复发的患者和只有渐进性恶化而没有复发的患者中可以看到。关于需要坐轮椅的时间、复发率和严重程度、类固醇治疗的次数和住院次数，以及磁共振成像变量，也获得了积极的结果。该药物是安全的，副作用与之前使用干扰素β-1b的经验一致。这项研究在中期结果提供了明确的疗效证据后停止。干扰素β-1b的解释治疗延缓了SP-MS患者持续的神经恶化。干扰素-β-1b是第一个对SP-MS患者显示疗效的治疗方法。
Background The beneficial effects of interferon beta have only been shown for patients in the relapsing-remitting phase of multiple sclerosis (MS). The role of interferon beta in the treatment of patients who are in the secondary progressive phase of the disease (SP-MS), and for whom no effective drug treatment is available, has not been assessed.Methods In this multicentre, double-masked, randomised, placebo-controlled trial, outpatients with SP-MS having scores of 3.0-6.5 on the Expanded Disability Status Scale (EDSS) received either 8 million IU interferon beta-1b every other day subcutaneously, or placebo, for up to 3 years. The primary outcome was the time to confirmed progression in disability as measured by a 1.0 point increase on the EDSS, sustained for at least 3 months, or a 0.5 point increase if the baseline EDSS was 6.0 or 6.5, A prospectively planned interim analysis of safety and efficacy of the intention-to-treat population was done after all patients had been in the study for at least 2 years.Findings 358 patients with SP-MS were allocated placebo and 360 were allocated interferon beta-1b; 57 patients (31 placebo, 26 interferon beta-1b) were lost to follow-up. There was a highly significant difference in time to confirmed progression of disability in favour of interferon beta-1b (p = 0.0008). Interferon beta-1b delayed progression for 9-12 months in a study period of 2-3 years. The odds ratio for confirmed progression was 0.65 (95% CI 0.52-0.83). This beneficial effect was seen in patients with superimposed relapses and in patients who had only progressive deterioration without relapses. Positive results were also obtained regarding time to becoming wheelchair-bound, relapse rate and severity, number of steroid treatments and hospital admissions, as well as on magnetic resonance imaging variables. The drug was safe and side effects were in line with previous experience with interferon beta-1b. The study was stopped after the interim results gave clear evidence of efficacy. interpretation Treatment with interferon beta-1b delays sustained neurological deterioration in patients with SP-MS.Interferon beta-1b is the first treatment to show a therapeutic effect in patients with SP-MS.