Clanet M, Radue E W, Kappos L, Hartung H P, Hohlfeld R, Sandberg-Wollheim M, Kooijmans-Coutinho M F, Tsao E C, Sandrock A W
Service de Neurologie, CHU Toulouse Purpan, Toulouse, France.
Neurology. 2002 Nov 26;59(10):1507-17. doi: 10.1212/01.wnl.0000032256.35561.d6.
Interferon beta-1a (IFNbeta-1a; Avonex) is effective for the treatment of relapsing MS; however, the optimal dose of IFNbeta-1a is not known.
To determine whether IFNbeta-1a 60 micro g IM once weekly is more effective than IFNbeta-1a 30 micro g IM once weekly in reducing disability progression in relapsing MS.
In a double-blind, parallel-group, dose-comparison study, 802 patients with relapsing MS from 38 centers in Europe were randomized to IFNbeta-1a 30 micro g (n = 402) or 60 micro g (n = 400) IM once weekly for >/=36 months. The primary endpoint was disability progression, defined as time to a sustained increase of >/=1.0 point on the Expanded Disability Status Scale (EDSS) persisting for 6 months. Additional endpoints included relapses, MRI, safety, immunogenicity, and subgroup analyses of disability progression.
Both groups showed equal rates of disability progression (hazard ratio, 0.96; 95% CI, 0.77 to 1.20; p = 0.73). In both groups the proportion of subjects with progression of disability by 36 months estimated from Kaplan-Meier curves was 37%. No dose effects were observed on any of the secondary clinical endpoints. Only one MRI measure at one time point, number of new or enlarging T2 lesions at month 36 compared with month 24, showed a difference favoring the 60- micro g dose. Both doses were well tolerated; however, slightly higher incidences of flulike symptoms and muscle weakness were observed in the 60- micro g group. The incidences of neutralizing antibodies (titers >/= 20) were 2.3% in the 30- micro g group and 5.8% in the 60- micro g group.
There was no difference between IFNbeta-1a 30 micro g and 60 micro g IM in clinical or MRI measures.
干扰素β-1a（IFNβ-1a；阿沃尼克斯）对复发型多发性硬化症（MS）的治疗有效；然而，IFNβ-1a的最佳剂量尚不清楚。
确定每周一次皮下注射60μg IFNβ-1a在减少复发型MS残疾进展方面是否比每周一次皮下注射30μg IFNβ-1a更有效。
在一项双盲、平行组、剂量对比研究中，来自欧洲38个中心的802例复发型MS患者被随机分为两组，分别接受每周一次皮下注射30μg（n = 402）或60μg（n = 400）IFNβ-1a，治疗时间≥36个月。主要终点是残疾进展，定义为扩展残疾状态量表（EDSS）持续增加≥1.0分并持续6个月的时间。其他终点包括复发、磁共振成像（MRI）、安全性、免疫原性以及残疾进展的亚组分析。
两组的残疾进展率相等（风险比，0.96；95%置信区间，0.77至1.20；p = 0.73）。根据Kaplan-Meier曲线估计，两组中在36个月时出现残疾进展的受试者比例均为37%。在任何次要临床终点上均未观察到剂量效应。仅在一个时间点的一项MRI测量中，即与第24个月相比，第36个月新出现或扩大的T2病变数量，显示60μg剂量组有优势。两种剂量耐受性均良好；然而，60μg组出现类似流感症状和肌肉无力的发生率略高。中和抗体（滴度≥20）的发生率在30μg组为2.3%，在60μg组为5.8%。
每周一次皮下注射30μg和60μg IFNβ-1a在临床或MRI测量方面没有差异。
