Neutralizing antibodies and efficacy of interferon β-1a -: A 4-year controlled study
Neutralizing antibodies and efficacy of interferon β-1a -: A 4-year controlled study
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DOI：
10.1212/01.wnl.0000171747.59767.5c
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发表时间：
2005-07-12
期刊：
影响因子：
9.9
通讯作者：
Goelz, S
中科院分区：
文献类型：
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作者：
Kappos, L;Clanet, M;Goelz, S
目的：确定参加欧洲干扰素 Beta-1a 肌注剂量比较研究的复发性多发性硬化症 (MS) 患者中和抗体 (NAb) 形成的发生率和临床意义。方法。患者被随机接受每周一次的干扰素β-1a (IFN beta-1a) 30μg或60μg肌肉注射治疗，持续长达4年。通过 ELISA 筛选基线时和此后每 3 个月获得的血清样本中是否存在 IFN 结合抗体。使用抗病毒细胞病变效应测定对 ELISA 结果呈血清阳性的患者进行筛查，以确定是否存在 NAb。如果基线 NAb 滴度为 0 并且连续两次或两次以上基线后滴度 >= 20，则患者被视为 NAbs (NAb+) 阳性。如果基线 NAb 滴度为 0 并且所有基线后 NAb 滴度 < 5，则患者被视为 NAbs (NAb -) 阴性。 结果：接受 30 μg IFN 治疗的患者中，变为 NAb + 的患者比例较低beta-1a 的含量高于接受 60 μg 剂量的患者（7/400 [1.8%] vs 19/395 [4.8%]；p = 0.02）。达到 NAb + 状态的平均时间为 14.5 +/- 6.2 个月。与保留 NAb - 的患者相比，NAb + 患者表现出以下特点：第 12 至 48 个月的复发率较高（p = 0.04），从基线到第 48 个月的扩展残疾状态量表评分平均变化率（恶化）较高（p = 0.01），第 24 和 36 个月时 T1 钆增强病变数量较多（p = 0.02 和 0.03），以及从第 12 个月到第 24 个月和第 36 个月，新的或扩大的 T2 病变增加（p = 0.05 和 0.09）。结论：与用于治疗多发性硬化症的其他 IFN β 一样，干扰素 β-1a (IFN β-1a) 的中和抗体 (NAb) 会降低通过复发和 MRI 活性衡量的治疗效果。这项研究的数据还表明，根据扩展残疾状态量表评分的变化来衡量，IFN beta-1a 的 NAb 会降低治疗效果。
Objective: To determine the incidence and clinical significance of neutralizing antibody (NAb) formation in patients with relapsing multiple sclerosis ( MS) who participated in the European Interferon Beta-1a IM Dose-Comparison Study. Methods. Patients were randomized to treatment with interferon beta-1a (IFN beta-1a) 30 mu g or 60 mu g IM once weekly for up to 4 years. Serum samples obtained at baseline and every 3 months thereafter were screened for the presence of IFN binding antibodies by ELISA. Patients whose results were seropositive on ELISA were screened for the presence of NAbs using an antiviral cytopathic effect assay. Patients were considered to be positive for NAbs ( NAb+) if the baseline NAb titer was 0 and two or more consecutive postbaseline titers were >= 20. Patients were considered to be negative for NAbs ( NAb -) if the baseline NAb titer was 0 and all postbaseline NAb titers were < 5. Results: The proportion of patients who became NAb + was lower in patients who received 30 mu g of IFN beta-1a than in those who received 60 mu g (7/400 [1.8%] vs 19/395 [4.8%]; p = 0.02). The mean time to NAb + status was 14.5 +/- 6.2 months. Compared with patients who remained NAb -, NAb + patients showed the following: higher relapse rates from months 12 to 48 ( p = 0.04), higher rate of mean change ( worsening) in Expanded Disability Status Scale score from baseline to month 48 ( p = 0.01), greater number of T1 gadolinium-enhanced lesions at months 24 and 36 ( p = 0.02 and 0.03), and greater accrual of new or enlarging T2 lesions from month 12 to months 24 and 36 ( p = 0.05 and 0.09) Conclusions: Neutralizing antibodies ( NAbs) to interferon beta-1a (IFN beta-1a), as observed with other IFN beta s used in the treatment of multiple sclerosis, reduce the therapeutic benefits measured by relapses and MRI activity. Data from this study also suggest NAbs to IFN beta-1a reduce treatment benefits as measured by change in Expanded Disability Status Scale score.