Koch-Henriksen N, Sorensen P S, Bendtzen K, Flachs E M
Department of Neurology, Aarhus University Hospital in Aalborg, Denmark and The Danish MS Treatment Register, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Mult Scler. 2009 May;15(5):601-5. doi: 10.1177/1352458508101946. Epub 2009 Mar 19.
To establish whether the clinical effect of neutralizing antibodies (NAbs) against interferon-beta (IFN beta) depends on the type of IFNbeta (1a or 1b) used for treatment of patients with relapsing-remitting multiple sclerosis (MS).
NAbs against IFN beta-1b appear faster and may be more evenly distributed on IgG subclasses, whereas NAbs against IFN beta-1a develop more slowly and may be devoid of IgG3. This might cause different clinical responses to NAbs.
DESIGN/PATIENTS: All Danish MS-patients who had started first-time treatment with IFNbeta-1a 22 microg s.c tiw (Rebif22) or IFN beta-1b 250 microg s.c. qod (Betaferon) before January 1st 2003 were included. Relapses were recorded at bi-annual visit.
We measured NAbs every 12 months using a clinically validated cytopathic effect assay. A blood sample with a neutralizing capacity of 20% or more was considered as NAb-positive. We used a mixed logistic regression analysis in which NAb-status (three levels), IFN beta-preparation, and time since treatment started were included as explanatory variables, and relapse rate as response variable.
In 1,309 patients, who were observed for 21,958 months, 32.3% were classified as NAb-positive. The odds-ratio (OR) for relapses in NAb-positive months compared with NAb-negative months was 1.25; P = 0.02. The risk of relapses was higher with Betaferon than with Rebif22 (OR 1.26; P < 0.01). The effect of NAb-level on relapses was independent of whether the patients were treated with Betaferon or Rebif22 (P = 0.89) and of time (P = 0.80).
NAbs caused by IFNbeta-1a s.c. do not differ from NAbs caused by IFNbeta-1b in their detrimental clinical effect.
确定针对干扰素-β(IFNβ)的中和抗体(NAbs)的临床效果是否取决于用于复发缓解型多发性硬化症(MS)患者治疗的IFNβ类型(1a或1b)。
针对IFNβ-1b的NAbs出现得更快,并且可能在IgG亚类上分布更均匀,而针对IFNβ-1a的NAbs产生得更慢,并且可能缺乏IgG3。这可能导致对NAbs的不同临床反应。
设计/患者:纳入了所有在2003年1月1日前首次开始使用22μg皮下注射、每周三次的IFNβ-1a(Rebif22)或250μg皮下注射、隔日一次的IFNβ-1b(Betaferon)进行治疗的丹麦MS患者。每半年随访时记录复发情况。
我们每12个月使用经过临床验证的细胞病变效应测定法测量NAbs。中和能力达到20%或更高的血样被视为NAb阳性。我们使用混合逻辑回归分析,将NAb状态(三个水平)、IFNβ制剂以及治疗开始后的时间作为解释变量,复发率作为反应变量。
在1309例患者中,观察了21958个月,32.3%被分类为NAb阳性。与NAb阴性月份相比,NAb阳性月份复发的比值比(OR)为1.25;P = 0.02。使用Betaferon时的复发风险高于使用Rebif22(OR 1.26;P < 0.01)。NAb水平对复发的影响与患者接受的是Betaferon还是Rebif22治疗无关(P = 0.89),也与时间无关(P = 0.80)。
皮下注射IFNβ-1a引起的NAbs与皮下注射IFNβ-1b引起的NAbs在有害临床效果方面没有差异。