Einarson Thomas R, Bereza Basil G, Machado Márcio
a Leslie Dan Faculty of Pharmacy , University of Toronto , Canada.
b Biogen Inc. , São Paulo , Brazil.
Curr Med Res Opin. 2017 Mar;33(3):579-593. doi: 10.1080/03007995.2016.1276895. Epub 2017 Jan 11.
Differences between interferons have been evaluated for over 20 years. While randomized controlled trial (RCT) data is mainly used for assessments and strong data for causal inferences, it does not necessarily reflect everyday practice. Real-world data may provide additional information.
To assess the results, quality, and representativeness of observational studies directly comparing interferons (IFNs) in RRMS.
Medline and Embase were searched for observational studies comparing IFN-beta-1a 30 mcg IM (Avonex ), IFN-beta-1a 44 mcg SC (Rebif ) and/or IFN-beta-1b 250 mcg SC (Betaseron ). Outcomes included annualized relapse rate (ARR), proportions relapse free, confirmed progression free, treatment persistence, and neutralizing antibodies rates (NABs) measured up to 5 years of treatment. Data was combined using random effects meta-analyses. Categorical values were analyzed using chi-squared and Mann-Whitney tests.
Thirty-six studies examining 32,026 patients (72.5% females, age = 39.2 ± 3.7 years, disease duration = 5.6 ± 2.0 years) were identified. Thirty-three studies investigated IFN-beta-1a IM (N = 11,925), 30 IFN-beta-1a SC (N = 10,684) and 34 IFN-beta-1b SC (N = 9417). Baseline ARRs were similar (1.37 ± 0.35, 1.51 ± 0.27 and 1.55 ± 0.23, respectively; P = .101) as were EDSS scores (2.24 ± 0.39, 2.33 ± 0.30, 2.55 ± 0.38; P = .070) and >75% were naïve to IFNs. On treatment, ARRs were comparable (IFN-beta-1a IM 0.52 ± 0.27, IFN-beta-1a SC 0.51 ± 0.24, IFN-beta-1b SC 0.55 ± 0.23; P = .595). Proportions of relapse-free patients were similar between drugs (P > .05 for all data points), except that IFN-beta-1a SC was superior to IFN-beta-1b SC in years 3-5 (all P ≤ .001). After 1 year, EDSS scores were comparable; after 2 years, IFN-beta-1a IM and IFN-beta-1a SC incurred less disease progression than IFN-beta-1b SC (P < .02). Confirmed progression-free rates and persistence were similar over 5 years. Fewer patients developed NABs with IFN-beta-1a IM (4.7 ± 1.5%) versus IFN-beta-1a SC (21.4 ± 2.8%) (P < 0.001) or IFN-beta-1b SC (32.2% ± 3.3%) (P < .001).
In this comprehensive meta-analysis of real-world studies in RRMS, IFN-beta-1a IM, IFN-beta-1a SC and IFN-beta-1b SC had similar clinical profiles. When selecting an IFN, practitioners should consider observational data in their decision making process.
对干扰素之间的差异已评估了20多年。虽然随机对照试验（RCT）数据主要用于评估以及因果推断的有力数据，但它不一定反映日常实践。真实世界数据可能提供额外信息。
评估直接比较复发缓解型多发性硬化症（RRMS）中干扰素（IFN）的观察性研究的结果、质量和代表性。
检索Medline和Embase数据库，查找比较30μg肌内注射（IM）的干扰素β-1a（阿沃尼）、44μg皮下注射（SC）的干扰素β-1a（利比）和/或250μg皮下注射的干扰素β-1b（倍泰龙）的观察性研究。结局包括年化复发率（ARR）、无复发比例、确诊无进展比例、治疗持续性以及治疗长达5年时的中和抗体率（NABs）。数据采用随机效应荟萃分析进行合并。分类变量采用卡方检验和曼-惠特尼检验进行分析。
共纳入36项研究，涉及32026例患者（72.5%为女性，年龄=39.2±3.7岁，疾病持续时间=5.6±2.0年）。33项研究调查了干扰素β-1a肌内注射（N=11925）、30项研究调查了干扰素β-1a皮下注射（N=10684）以及34项研究调查了干扰素β-1b皮下注射（N=9417）。基线ARR相似（分别为1.37±0.35、1.51±0.27和1.55±0.23；P=0.101），扩展残疾状态量表（EDSS）评分也相似（2.24±0.39、2.33±0.30、2.55±0.38；P=0.070），且超过75%的患者既往未使用过干扰素。治疗期间，ARR具有可比性（干扰素β-1a肌内注射0.52±0.27，干扰素β-1a皮下注射0.51±0.24，干扰素β-1b皮下注射0.55±0.23；P=0.595）。各药物之间无复发患者比例相似（所有数据点P>0.05），但在第3至5年，干扰素β-1a皮下注射优于干扰素β-1b皮下注射（所有P≤0.001）。1年后，EDSS评分具有可比性；2年后，干扰素β-1a肌内注射和干扰素β-1a皮下注射比干扰素β-1b皮下注射的疾病进展更少（P<0.02）。5年期间确诊无进展率和持续性相似。与干扰素β-1a皮下注射（21.4±2.8%）（P<0.001）或干扰素β-1b皮下注射（32.2%±3.3%）（P<0.001）相比，使用干扰素β-1a肌内注射产生NABs的患者更少（4.7±1.5%）。
在这项针对RRMS真实世界研究的综合荟萃分析中，干扰素β-1a肌内注射、干扰素β-1a皮下注射和干扰素β-1b皮下注射具有相似的临床特征。在选择干扰素时，临床医生应在决策过程中考虑观察性数据。
