Millonig A, Rudzki D, Hölzl M, Ehling R, Gneiss C, Künz B, Berger T, Reindl M, Deisenhammer F
Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
Mult Scler. 2009 Aug;15(8):977-83. doi: 10.1177/1352458509105384. Epub 2009 May 22.
Neutralizing antibodies (NABs) against interferon beta (IFNbeta) are associated with a loss of IFNbeta bioactivity and clinical effectiveness. To date, there are no anti-NAB strategies available. The primary objective of this trial was to investigate whether intravenous IFNbeta-1b can restore bioactivity in NAB-positive patients with MS.
NAB-positive patients with MS were treated with 8 MIU IFNbeta-1b s.c., 8 MIU i.v., and 16 MIU i.v. Each application was preceded by a wash-out period of 1 week. Blood samples were collected before, 3, 12, and 24 h after each administration. Myxovirus protein A (MxA) RNA and protein levels were determined. The study has been approved by the local ethics committee.
Five patients completed the study. NAB titers ranged from 42 to 4482 neutralizing units. Median MxA protein (1821, range 12-3234) and RNA (2186, range 114-7525) area under the curve levels for the four measurements at each IFNbeta injection were significantly higher after i.v. application of 16 MIU as compared with both 8-MIU dosages, which were 743 (0-2709) for MxA protein after 8 MIU i.v. and 254 (0-1200) after s.c., and 1763 (25-7188) for MxA RNA after 8 MIU i.v., and 557 (5-2265) after s.c. applications. NAB titers decreased significantly and transiently after infusion of 16 MIU IFNbeta-1b but not after both forms of 8 MIU applications. Typical side effects could be controlled by paracetamol. No allergic reaction was observed.
The results indicate that i.v. administration of IFNbeta can restore bioavailability of IFNbeta in patients with NABs.
抗干扰素β（IFNβ）中和抗体（NABs）与IFNβ生物活性丧失及临床疗效相关。迄今为止，尚无可用的抗NAB策略。本试验的主要目的是研究静脉注射IFNβ-1b能否恢复NAB阳性多发性硬化症（MS）患者的生物活性。
NAB阳性的MS患者分别接受8百万国际单位（MIU）皮下注射、8 MIU静脉注射和16 MIU静脉注射的IFNβ-1b治疗。每次用药前均有1周的洗脱期。在每次给药前、给药后3小时、12小时和24小时采集血样。测定黏液病毒蛋白A（MxA）的RNA和蛋白水平。本研究已获得当地伦理委员会批准。
5名患者完成了研究。NAB滴度范围为42至4482中和单位。每次IFNβ注射时，4次测量的MxA蛋白曲线下面积中位数（1821，范围12 - 3234）和RNA（2186，范围114 - 7525）在静脉注射16 MIU后显著高于8 MIU的两种剂量，8 MIU静脉注射后MxA蛋白为743（0 - 2709），皮下注射后为254（0 - 1200）；8 MIU静脉注射后MxA RNA为1763（25 - 7188），皮下注射后为557（5 - 2265）。输注16 MIU IFNβ-1b后NAB滴度显著且短暂下降，但8 MIU的两种给药方式均未出现此情况。典型的副作用可用对乙酰氨基酚控制。未观察到过敏反应。
结果表明，静脉注射IFNβ可恢复NAB阳性患者体内IFNβ的生物利用度。
