Randomized controlled trial of interferon- beta-1a in secondary progressive MS
Randomized controlled trial of interferon- beta-1a in secondary progressive MS
复制标题
干扰素-β-1a 治疗继发性进展型多发性硬化症的随机对照试验
作者：
Kyösti Kauppinen;J. Pylväläinen;K. Pamilo;O. Helminen;M. Haapea;S. Saarakkala;M. Nevalainen
背景：干扰素β对复发缓解型多发性硬化症加重的有益作用已被反复证实，但与残疾有关的结果各不相同。目的：这项多中心、随机、平行组、安慰剂对照的研究测试了两种剂量的干扰素β -1a对继发性进展性多发性硬化症患者的治疗作用，这些患者可能包括复发，但主要是累积性残疾。方法：618例患者接受皮下安慰剂或干扰素β -1a、22或44 μg治疗，每周3次，连续3年。每3个月对患者进行一次评估。结果：主要结局，确认残疾进展的时间，不受治疗的显著影响（风险比为0.83；95% CI为0.65至1.07；44 μg与安慰剂相比p = 0.146）。复发率从安慰剂组的每年0.71降低到治疗组的每年0.50（两种剂量均p < 0.001）。在其他与恶化相关的结果和包含五个独立临床和MRI结果的综合测量中，观察到显著的治疗效果。在研究前2年内复发的患者中，联合干扰素β -1a组与安慰剂组的进展时间风险比为0.74 (p = 0.055)，而在研究前无复发的患者中，风险比为1.01 （p = 0.934）。一种意想不到的性别治疗对女性有利。这种药耐受性很好。结论：在该队列中，干扰素β -1a治疗没有显著影响残疾进展，尽管在恶化相关的结局中观察到显著的治疗获益。探索性事后分析表明，在研究前2年内至少有一次复发的女性和患者获益更大。
Background: The beneficial effect of interferon beta on exacerbations in relapsing-remitting MS has been demonstrated repeatedly, but results concerning disability vary. Objective: This multicenter, randomized, parallel-group, placebo-controlled study tested two doses of interferon beta-1a in patients with secondary progressive MS, which may include relapses but is dominated by accumulating disability. Methods: A total of 618 patients received subcutaneous placebo or interferon beta-1a, 22 or 44 μg three times weekly for 3 years. Patients were assessed every 3 months. Results: The primary outcome, time to confirmed progression in disability, was not significantly affected by treatment (hazard ratio, 0.83; 95% CI, 0.65 to 1.07; p = 0.146 for 44 μg versus placebo). Relapse rate was reduced from 0.71 per year with placebo to 0.50 per year with treatment (p < 0.001 for both doses). Significant treatment effects were seen on other exacerbation-related outcomes and on a composite measure incorporating five separate clinical and MRI outcomes. The hazard ratio for time to progression for the combined interferon beta-1a groups compared with placebo was 0.74 among patients reporting relapses in the 2 years before study (p = 0.055), and 1.01 for those without prestudy relapses (p = 0.934). An unexpected treatment-by-sex interaction favored women. The drug was well tolerated. Conclusions: Treatment with interferon beta-1a did not significantly affect disability progression in this cohort, although significant treatment benefit was observed on exacerbation-related outcomes. Exploratory post hoc analyses suggested greater benefit in women and in patients who had reported at least one relapse in the 2 years before the study.