Kappos Ludwig, Freedman Mark S, Polman Chris H, Edan Gilles, Hartung Hans-Peter, Miller David H, Montalbán Xavier, Barkhof Frederik, Radü Ernst-Wilhelm, Bauer Lars, Dahms Susanne, Lanius Vivian, Pohl Christoph, Sandbrink Rupert
Neurology and Department of Research, University Hospital, Basel, Switzerland.
Lancet. 2007 Aug 4;370(9585):389-97. doi: 10.1016/S0140-6736(07)61194-5.
Several controlled studies provide evidence that treatment with interferon beta in patients with a first event suggestive of multiple sclerosis (MS) delays conversion to clinically definite MS (CDMS). Our aim was to determine whether early initiation of treatment with interferon beta prevents development of confirmed disability in MS.
In the initial placebo-controlled phase of the double-blinded BENEFIT study, patients with a first event suggestive of MS and a minimum of two clinically silent lesions in MRI were randomised to receive either interferon beta-1b 250 microg (n=292) or placebo (n=176) subcutaneously every other day for 2 years, or until diagnosis of CDMS. Patients were then eligible to enter the follow-up phase with open-label interferon beta-1b. In the current prospectively planned analysis 3 years after randomisation, the effects of early interferon beta-1b treatment were compared with those of delayed treatment initiated after diagnosis of CDMS or after 2 years on the study. The primary outcomes of this ITT analysis were time to diagnosis of CDMS, time to confirmed expanded disability status scale (EDSS) progression, and score on a patient-reported functional assessment scale (FAMS-TOI). This trial is registered with ClinicalTrials.gov, number NCT00185211.
Of the 468 patients originally randomised, 418 (89%) entered the follow-up phase; 392 (84%) completed 3 years' post-randomisation follow-up. After 3 years, 99 (37%) patients in the early group developed CDMS compared with 85 (51%) patients in the delayed treatment group. Early treatment reduced the risk of CDMS by 41% (hazard ratio 0.59, 95% CI 0.44-0.80; p=0.0011; absolute risk reduction 14%) compared with delayed treatment. Over 3 years, 42 (16%) patients in the early group and 40 (24%) in the delayed group had confirmed EDSS progression; early treatment reduced the risk for progression of disability by 40% compared with delayed treatment (0.60, 0.39-0.92; p=0.022; absolute risk reduction 8%). The FAMS-TOI score was high and stable in both groups over the 3-year period (p=0.31).
Our data suggest that early initiation of treatment with interferon beta-1b prevents the development of confirmed disability, supporting its use after the first manifestation of relapsing-remitting MS.
多项对照研究表明，对首次出现提示多发性硬化（MS）症状的患者使用β-干扰素进行治疗，可延缓其转变为临床确诊的多发性硬化（CDMS）。我们的目的是确定早期开始使用β-干扰素治疗是否能预防MS患者出现确诊的残疾。
在双盲BENEFIT研究的初始安慰剂对照阶段，将首次出现提示MS症状且MRI至少有两个临床无症状病灶的患者随机分为两组，一组每隔一天皮下注射250微克β-1b干扰素（n = 292），另一组注射安慰剂（n = 176），持续2年，或直至诊断为CDMS。之后患者有资格进入开放标签的β-1b干扰素随访阶段。在随机分组3年后进行的本次前瞻性计划分析中，将早期使用β-1b干扰素治疗的效果与在诊断为CDMS后或研究进行2年后开始的延迟治疗效果进行比较。这项意向性分析的主要结局指标为诊断为CDMS的时间、确诊的扩展残疾状态量表（EDSS）进展时间以及患者报告的功能评估量表（FAMS-TOI）得分。该试验已在ClinicalTrials.gov注册，注册号为NCT00185211。
最初随机分组的468例患者中，418例（89%）进入随访阶段；392例（84%）完成了随机分组后3年的随访。3年后，早期治疗组有99例（37%）患者发展为CDMS，而延迟治疗组有85例（51%）患者发展为CDMS。与延迟治疗相比，早期治疗使CDMS风险降低了41%（风险比0.59，95%可信区间0.44 - 0.80；p = 0.0011；绝对风险降低14%）。在3年期间，早期治疗组有42例（16%）患者确诊EDSS进展，延迟治疗组有40例（24%）；与延迟治疗相比，早期治疗使残疾进展风险降低了40%（0.60，0.39 - 0.92；p = 0.022；绝对风险降低8%）。在3年期间，两组的FAMS-TOI得分均较高且稳定（p = 0.31）。
我们的数据表明，早期开始使用β-1b干扰素治疗可预防确诊残疾的发生，支持在复发缓解型MS首次出现症状后使用该药物。
