Neurology. 1996 Oct;47(4):889-94. doi: 10.1212/wnl.47.4.889.
Evidence of diminution of therapeutic efficacy in 35% of interferon beta-1b (IFNB)-treated multiple sclerosis (MS) patients who developed neutralizing antibodies (NABs) led to extensive study of the effects of NABs on therapeutic benefits, side effects, and magnetic resonance imaging (MRI) data. First, we validated the IFNB NAB assay used in the multicenter trial by having representative stored serum samples reanalyzed by an independent laboratory. When NABs developed (as defined), usually in the first year, the exacerbation rates after 18 months resembled placebo rates, the numbers of enlarging MRI lesions significantly increased compared with those in NAB-negative patients, and there was increased new lesion formation in the MRI (p = 0.067). However, worsening of the mean Expanded Disability Status Scale score in the 8-MIU treatment arm was higher in patients who remained NAB-negative in the third year (p = 0.083). NAB-positive patients were not overrepresented among the noncompleters, or in five patients having at least one episode of skin-site necrosis. After 18 months, flu-like symptoms were about twice as common in NAB-negative as in NAB-positive patients, although the frequency did not exceed 21% in any semester. Decisions to discontinue IFNB therapy should be made individually based on clinical response and a positive titer of NABs in the serum with the use of a reliable assay. ELISA and Western blot techniques measure binding antibodies, not NABs specifically, and are unsuitable for use. Possible, but as yet unproven, means of dealing with NAB positivity should be studied in properly designed trials. IFNB-1b remains an effective therapy for a majority (65%) of MS patients having relapses. The annual exacerbation rates in NAB-negative patients receiving the 8-MIU dosage regimen are about 50% of those seen in untreated patients, a greater reduction than the one-third reduction earlier reported for the entire high-dose arm, and a meaningful treatment benefit.
在35%接受β-1b干扰素（IFNB）治疗的多发性硬化症（MS）患者中出现了治疗效果下降的证据，这些患者产生了中和抗体（NABs），这引发了对NABs对治疗益处、副作用及磁共振成像（MRI）数据影响的广泛研究。首先，我们通过让一个独立实验室重新分析具有代表性的储存血清样本，验证了多中心试验中使用的IFNB NAB检测方法。当NABs产生时（按定义），通常在第一年，18个月后的病情加重率类似于安慰剂组，与NAB阴性患者相比，MRI上扩大的病灶数量显著增加，且MRI上新病灶形成增多（p = 0.067）。然而，在第三年仍为NAB阴性的患者中，8 MIU治疗组的平均扩展残疾状态量表评分恶化程度更高（p = 0.083）。在未完成治疗的患者中，或在至少有一次皮肤部位坏死发作的5名患者中，NAB阳性患者并未占过高比例。18个月后，NAB阴性患者中流感样症状的发生率约为NAB阳性患者的两倍，尽管在任何一个学期中该频率均未超过21%。应根据临床反应以及血清中NABs的阳性滴度（使用可靠检测方法），个体化地做出停用IFNB治疗的决定。酶联免疫吸附测定（ELISA）和蛋白质印迹技术测量的是结合抗体，而非特异性的NABs，不适于使用。应对NAB阳性的可能方法（但尚未得到证实）应在设计合理的试验中进行研究。IFNB-1b对大多数（65%）复发型MS患者仍是一种有效的治疗方法。接受8 MIU剂量方案的NAB阴性患者的年病情加重率约为未治疗患者的50%，降低幅度大于先前报道的整个高剂量组三分之一的降低幅度，具有显著的治疗益处。
