Department of Neurology, Ospedale San Raffaele, Milan, Italy.
Lancet Neurol. 2012 Jan;11(1):33-41. doi: 10.1016/S1474-4422(11)70262-9. Epub 2011 Dec 4.
In patients presenting with a first clinical demyelinating event that is suggestive of multiple sclerosis (MS), treatment with interferon beta can delay the occurrence of further attacks and the onset of MS. We investigated the effects of two dosing frequencies of subcutaneous interferon beta-1a in patients with a first clinical demyelinating event.
We undertook a multicentre phase 3 study (REbif FLEXible dosing in early MS [REFLEX]) that included patients (aged 18-50 years) with a single clinical event suggestive of MS, and at least two clinically silent T2 lesions on brain MRI. Participants were randomly assigned in a 1:1:1 ratio by use of a centralised interactive voice response system to receive the serum-free formulation of subcutaneous interferon beta-1a 44 μg three times a week or once a week (plus placebo twice a week for masking), or placebo three times a week for up to 24 months. Patients and physicians were masked to group allocation. The primary endpoint was time to a diagnosis of MS as defined by the 2005 McDonald criteria and the main secondary endpoint was time to clinically definite MS (CDMS) as defined by the Poser criteria. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00404352.
517 patients were randomly assigned (171 to subcutaneous interferon beta-1a three times a week, 175 to subcutaneous interferon beta-1a once a week, and 171 to placebo) and 515 were treated. The 2-year cumulative probability of McDonald MS was significantly lower in patients treated with subcutaneous interferon beta-1a (three times a week 62·5%, p<0·0001, hazard ratio [HR] 0·49 [95% CI 0·38-0·64]; once a week 75·5%, p=0·008, HR 0·69 [0·54-0·87]) versus placebo (85·8%). 2-year rates of conversion to CDMS were lower for both interferon beta-1a dosing regimens (three times a week 20·6%, p=0·0004, HR 0·48 [0·31-0·73]; once a week 21·6%, p=0·0023, HR 0·53 [0·35-0·79]) than for placebo (37·5%). Adverse events were within the established profile for subcutaneous interferon beta-1a.
Both regimens of subcutaneous interferon beta-1a delayed clinical relapses and subclinical disease activity. The potential differences between the regimens warrant longer-term study.
Merck Serono SA, Geneva, Switzerland.
在出现首次临床脱髓鞘事件且提示多发性硬化（MS）的患者中，使用干扰素β治疗可延迟进一步发作和 MS 的发病。我们研究了两种皮下给予干扰素β-1a 的剂量方案在首次临床脱髓鞘事件患者中的效果。
我们开展了一项多中心 3 期研究（早期 MS 中 Rebif 的灵活剂量[REFLEX]），纳入了年龄为 18-50 岁、有单一提示 MS 的临床事件和至少 2 个脑 MRI 上无临床症状的 T2 病灶的患者。通过中央互动语音应答系统，以 1:1:1 的比例随机分配患者接受无血清制剂的皮下干扰素β-1a，每周 3 次或每周 1 次（每周 2 次给予安慰剂以掩盖），或每周 3 次接受安慰剂，最长 24 个月。患者和医生对分组分配均不知情。主要终点是根据 2005 年 McDonald 标准诊断为 MS 的时间，主要次要终点是根据 Poser 标准诊断为临床确诊 MS（CDMS）的时间。分析采用意向治疗。该研究在 ClinicalTrials.gov 注册，编号为 NCT00404352。
517 例患者被随机分配（每周 3 次皮下干扰素β-1a 171 例，每周 1 次皮下干扰素β-1a 175 例，安慰剂 171 例），515 例患者接受了治疗。与安慰剂相比，接受皮下干扰素β-1a 治疗的患者（每周 3 次组 62.5%，p<0.0001，风险比[HR]0.49[95%CI 0.38-0.64]；每周 1 次组 75.5%，p=0.008，HR 0.69[0.54-0.87]）2 年累积 McDonald MS 概率显著降低。两种干扰素β-1a 剂量方案的转 CDMS 率均较低（每周 3 次组 20.6%，p=0.0004，HR 0.48[0.31-0.73]；每周 1 次组 21.6%，p=0.0023，HR 0.53[0.35-0.79]），低于安慰剂组（37.5%）。不良反应与皮下干扰素β-1a 的既定特征一致。
两种皮下干扰素β-1a 方案均延迟了临床复发和临床前疾病活动。方案之间的潜在差异需要进行更长期的研究。
瑞士日内瓦默克雪兰诺有限公司。
