Benefit of interferon &bgr;-1a on MSFC progression in secondary progressive MS
Benefit of interferon &bgr;-1a on MSFC progression in secondary progressive MS
复制标题
干扰素的好处
作者：
Jeffrey A. Cohen;G. Cutter;J. Fischer;A. Goodman;F. Heidenreich;M. Kooijmans;A. Sandrock;R. Rudick;J. Simon;N. Simonian;E. Tsao;J. Whitaker
背景干扰素β-1a（IFNβ-1a，Avonex）对复发型多发性硬化症有效。其他干扰素的研究&bgr;继发性进展型 MS (SPMS) 的准备工作产生了相互矛盾的结果。本研究旨在确定 IFNβ-1a 是否能减缓 SP-MS 中的疾病进展。方法共有 436 名 SPMS 且扩展残疾状态量表 (EDSS) 评分为 3.5 至 6.5 的受试者随机接受 IFN&bgr;-1a (60 µg) 或安慰剂，每周肌内注射，为期 2 年。主要结局指标首次在大规模多发性硬化症试验中使用，是第 24 个月 MS 功能综合 (MSFC) 变化的基线，包括步行定量测试（定时 25 英尺步行）、手臂功能（九孔钉测试 [9HPT]）和认知（节奏听觉串行附加测试 [PASAT]）。结果 IFNβ-1a 受试者的中位 MSFC Z 分数变化降低了 40.4%（安慰剂受试者为 -0.096 对比 -0.161，p = 0.033），这一效应主要由 9HPT 和 PASAT 驱动。 EDSS 没有明显的好处，在此范围内主要反映步行能力。 IFNβ-1a 受试者的复发率减少了 33% (p = 0.008)。 MS 生活质量量表的 11 个分量表中有 8 个分量表显着受益。新的或扩大的 T2 高信号脑 MRI 病变和钆增强病变在第 12 个月和第 24 个月时减少（均 p < 0.001）。大多数受试者对 IFNβ-1a 的耐受性良好。 3.3% 接受 IFNβ-1a 治疗的受试者产生中和抗体。结论 IFNβ-1a 显示出对 SPMS 中 MSFC 进展、复发、生活质量和 MRI 活性的益处。
BackgroundInterferon &bgr;-1a (IFN&bgr;-1a, Avonex) is efficacious in relapsing forms of MS. Studies of other IFN&bgr; preparations in secondary progressive MS (SPMS) yielded conflicting results. This study was undertaken to determine whether IFN&bgr;-1a slowed disease progression in SP-MS. MethodsA total of 436 subjects with SPMS and Expanded Disability Status Scale (EDSS) score 3.5 to 6.5 were randomized to receive IFN&bgr;-1a (60 &mgr;g) or placebo by weekly intramuscular injection for 2 years. The primary outcome measure, used for the first time in a large-scale MS trial, was baseline to month 24 change in the MS Functional Composite (MSFC), comprising quantitative tests of ambulation (Timed 25-Foot Walk), arm function (Nine-Hole Peg Test [9HPT]), and cognition (Paced Auditory Serial Addition Test [PASAT]). ResultsMedian MSFC Z-score change was reduced 40.4% in IFN&bgr;-1a subjects (−0.096 vs −0.161 in placebo subjects, p = 0.033), an effect driven mainly by the 9HPT and PASAT. There was no discernible benefit on the EDSS, which in this range principally reflects walking ability. IFN&bgr;-1a subjects had 33% fewer relapses (p = 0.008). There was significant benefit on eight of 11 MS Quality of Life Inventory subscales. New or enlarging T2-hyperintense brain MRI lesions and gadolinium-enhancing lesions were reduced at months 12 and 24 (both p < 0.001). IFN&bgr;-1a was well tolerated by the majority of subjects. Neutralizing antibodies developed in 3.3% of IFN&bgr;-1a–treated subjects. ConclusionsIFN&bgr;-1a demonstrated benefit on MSFC progression, relapses, quality of life, and MRI activity in SPMS.