Brod S A, Lindsey J W, Vriesendorp F S, Ahn C, Henninger E, Narayana P A, Wolinsky J S
Department of Neurology, University of Texas-Houston, 77225, USA.
Neurology. 2001 Sep 11;57(5):845-52. doi: 10.1212/wnl.57.5.845.
To investigate whether ingested human recombinant interferon-alpha2a (IFN-alpha2a) was safe and whether treatment reduces the number of gadolinium-enhanced lesions on serial MRI in patients with active relapsing-remitting MS (RRMS).
Entry criteria included clinically definite RRMS and one or more gadolinium-enhanced lesions on a screening MRI.
Of 80 patients screened, 33 were eligible and 30 patients were enrolled for treatment. Patients were randomized (10 per group) to placebo, 10,000 or 30,000 IU IFN-alpha2a ingested on alternate days for 9 months. They were examined clinically and with monthly cerebral MRI. Sample size projections were based on the assumption of a parenteral IFN-like effect, a 90% reduction of enhancing lesions evident within 1 month of the initiation of treatment in the active treatment groups sustained during the 9-month study as the primary outcome variable.
There was no significant effect on enhancing lesions. However, post hoc analysis suggested a possible treatment effect in the 10,000 IU group. By direct monthly comparison of placebo and 10,000 IU group in treatment month 5, there were 73% (p < 0.05) fewer enhancements in the 10,000 IU group than in the placebo group. There was a decrease of tumor necrosis factor-alpha protein secretion at months 4 and 5. Relapses and adverse events were not different among the treatment groups. Ingested IFN-alpha2a did not induce systemic anti-IFN-alpha antibodies.
This trial showed no benefit based on the primary outcome measure. Because changes were detected in immune response and post hoc analysis suggested that a smaller dose could have an effect, IFN-alpha may deserve further study.
探讨口服重组人α2a干扰素（IFN-α2a）是否安全，以及该治疗方法能否减少复发缓解型多发性硬化症（RRMS）患者在系列磁共振成像（MRI）检查中钆增强病灶的数量。
入选标准包括临床确诊的RRMS以及筛查MRI上有一个或多个钆增强病灶。
在80例接受筛查的患者中，33例符合条件，30例患者入选接受治疗。患者被随机分组（每组10例），分别给予安慰剂、隔日口服10000或30000国际单位（IU）IFN-α2a，为期9个月。对患者进行临床检查并每月进行脑部MRI检查。样本量预测基于肠道外给予IFN类似效应的假设，即作为主要结局变量，在9个月的研究期间，活性治疗组在治疗开始后1个月内增强病灶明显减少90%并持续。
对增强病灶无显著影响。然而，事后分析提示10000 IU组可能存在治疗效果。在治疗第5个月时，通过直接逐月比较安慰剂组和10000 IU组发现，10000 IU组的增强病灶比安慰剂组少73%（p<0.05）。在第4个月和第5个月时肿瘤坏死因子-α蛋白分泌减少。各治疗组之间的复发率和不良事件无差异。口服IFN-α2a未诱导产生全身性抗IFN-α抗体。
基于主要结局指标，该试验未显示出益处。由于检测到免疫反应有变化，且事后分析提示较小剂量可能有效，IFN-α可能值得进一步研究。
