Danish Multiple Sclerosis Research Center, University of Copenhagen and Department of Neurology, Rigshospitalet, Copenhagen, Denmark.
Lancet Neurol. 2010 Jul;9(7):672-80. doi: 10.1016/S1474-4422(10)70132-0. Epub 2010 Jun 9.
Interferon beta is commonly used to treat patients with relapsing-remitting multiple sclerosis; however, the treatment is only partially effective in reducing relapses and progression of disability. Corticosteroids are used to treat relapses in patients with multiple sclerosis. We therefore aimed to investigate the combination of cyclic methylprednisolone and interferon beta for the treatment of relapsing-remitting multiple sclerosis.
In 2001, we designed a multicentre, double-blind, randomised, parallel-group trial, termed the methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN) study. Patients were recruited between October, 2002, and March, 2005 from 50 neurology departments in eight countries. We included treatment-naive patients with relapsing-remitting multiple sclerosis who had an expanded disability status scale (EDSS) score of 4 or less. Patients all started to receive interferon beta-1a and after 3 months were randomly assigned to add-on methylprednisolone or placebo 500 mg/day orally for 3 consecutive days per month for 3-4 years. Placebo tablets were identical to methylprednisolone tablets. Treating physicians, examining physicians, and patients were masked to treatment allocation. Patients were clinically assessed every 3 months and had brain MRI at baseline and 3 years later. The primary outcome was time to onset of disability progression, according to an increase in EDSS score sustained over 6 months. All patients who received at least one dose of study drug were included in all planned analyses. This trial is registered with ClinicalTrials.gov, NCT00168766.
341 patients were randomly assigned to methylprednisolone (n=172) or placebo (n=169); 171 patients in the methylprednisolone group and 167 in the placebo group received at least one dose of study drug. 90 patients had sustained disability progression: 44 of 167 in the methylprednisolone group and 46 of 171 in the placebo group. The time to sustained progression did not differ between groups (hazard ratio 0.879, 95% CI 0.566-1.365; p=0.57). There were 1436 adverse events, 24 of which were serious, in the methylprednisolone group and 1070 events, 35 of which were serious, in the placebo group.
Monthly pulses of methylprednisolone in combination with interferon beta-1a do not seem to affect disability progression any more than interferon beta-1a treatment alone. More research is required to assess whether this treatment regimen might benefit particular subsets of patients.
Biogen Idec.
干扰素 β 常用于治疗复发缓解型多发性硬化症患者；然而，它在减少复发和残疾进展方面的疗效仅部分有效。皮质类固醇用于治疗多发性硬化症患者的复发。因此，我们旨在研究环甲基泼尼松龙与干扰素 β-1a 联合治疗复发缓解型多发性硬化症。
2001 年，我们设计了一项多中心、双盲、随机、平行组试验，称为甲基泼尼松龙联合干扰素 β-1a 治疗复发缓解型多发性硬化症（MECOMBIN）研究。2002 年 10 月至 2005 年 3 月，来自八个国家的 50 个神经病学部门招募了治疗初治的复发缓解型多发性硬化症患者，他们的扩展残疾状况量表（EDSS）评分为 4 或更低。所有患者均开始接受干扰素 β-1a 治疗，3 个月后随机分配加用甲基泼尼松龙或安慰剂，每天口服 500mg，连续 3 天，持续 3-4 年。安慰剂片剂与甲基泼尼松龙片剂相同。治疗医生、检查医生和患者均对治疗分配进行了盲法。患者每 3 个月进行一次临床评估，并在基线和 3 年后进行脑 MRI。主要结局是根据 EDSS 评分持续增加 6 个月以上而发生残疾进展的时间。所有接受至少一剂研究药物的患者均纳入所有计划分析中。该试验在 ClinicalTrials.gov 注册，NCT00168766。
341 名患者被随机分配至甲基泼尼松龙（n=172）或安慰剂（n=169）组；甲基泼尼松龙组中有 171 名患者和安慰剂组中有 167 名患者接受了至少一剂研究药物。90 名患者出现持续残疾进展：甲基泼尼松龙组 44 名，安慰剂组 46 名。两组之间持续进展的时间没有差异（风险比 0.879，95%CI 0.566-1.365；p=0.57）。甲基泼尼松龙组有 1436 例不良事件，24 例为严重不良事件，安慰剂组有 1070 例不良事件，35 例为严重不良事件。
每月给予甲基泼尼松龙脉冲联合干扰素 β-1a 治疗似乎不会比单独使用干扰素 β-1a 治疗更能影响残疾进展。需要进一步研究以评估这种治疗方案是否可能使某些特定患者群体受益。
Biogen Idec。
