Lancet. 1998 Nov 7;352(9139):1491-7.
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.
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.
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.
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.
干扰素β的有益作用仅在复发缓解型多发性硬化症（MS）患者中得到证实。对于疾病处于继发进展期（SP-MS）且尚无有效药物治疗的患者，干扰素β在治疗中的作用尚未得到评估。
在这项多中心、双盲、随机、安慰剂对照试验中，扩展残疾状态量表（EDSS）评分在3.0 - 6.5之间的SP-MS门诊患者，每隔一天皮下注射800万国际单位干扰素β-1b或安慰剂，持续3年。主要结局是确认残疾进展的时间，以EDSS评分增加1.0分且持续至少3个月来衡量，若基线EDSS为6.0或6.5，则以增加0.5分来衡量。在所有患者入组研究至少2年后，对意向性治疗人群的安全性和疗效进行了一项预先计划的中期分析。
358例SP-MS患者被分配接受安慰剂，360例被分配接受干扰素β-1b；57例患者（31例接受安慰剂，26例接受干扰素β-1b）失访。在确认残疾进展的时间方面，干扰素β-1b组有极显著差异（p = 0.0008）。在2至3年的研究期内，干扰素β-1b将进展延迟了9至12个月。确认进展的比值比为0.65（95%可信区间0.52 - 0.83）。在有叠加复发的患者以及仅出现进行性恶化而无复发的患者中均观察到这种有益效果。在达到需使用轮椅的时间、复发率及严重程度、类固醇治疗次数和住院次数以及磁共振成像变量方面也取得了阳性结果。该药物安全，副作用与先前使用干扰素β-1b的经验一致。在中期结果提供了明确的疗效证据后，该研究提前终止。
干扰素β-1b治疗可延缓SP-MS患者持续的神经功能恶化。干扰素β-1b是首个在SP-MS患者中显示出治疗效果的药物。
