Sominanda A, Rot U, Suoniemi M, Deisenhammer F, Hillert J, Fogdell-Hahn A
Department of Clinical Neuroscience, Division of Neurology R54, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
Mult Scler. 2007 Mar;13(2):208-14. doi: 10.1177/1352458506070762. Epub 2007 Jan 29.
Development of neutralizing antibodies (NAbs) reduces the clinical efficacy of interferon beta (IFNbeta) treatment in multiple sclerosis (MS) patients. The aim of this study was to evaluate NAb seroprevalence (frequency of patients with NAbs) and immunogenicity (titer levels) of IFNbeta preparations in a clinical setting. We analysed 1115 consecutive MS patients, treated with one of the three available IFNbeta preparations, for an average of 40 months (1-120 months), for the presence of NAbs with the MxA protein induction assay. Overall, 32% of patients were positive for NAbs with neutralizing titers above 10. The frequency of NAbs, ie, the seroprevalence, was 13% in Avonex-treated patients, 43% for Betaferon, 39% for Rebif22 and 30% for Rebif44. In addition, the potential to induce high titer levels, ie, the immunogenicity, was observed to differ between preparations. Avonex, showing the lowest seroprevalence, also showed low immunogenicity and typically induced low titers. Betaferon, showing the highest seroprevalence when inducing NAbs, induced lower titers compared to Rebif22 and Rebif44. Treatment duration over five years only marginally correlated with decreased seroprevalence and titer levels. In conclusion, NAbs to IFNbeta are common in a clinical setting and the IFNbeta preparations differ not only in NAb seroprevalence, but also in immunogenicity.
中和抗体(NAbs)的产生会降低干扰素β(IFNβ)治疗多发性硬化症(MS)患者的临床疗效。本研究旨在评估临床环境中IFNβ制剂的NAb血清阳性率(NAb阳性患者的频率)和免疫原性(滴度水平)。我们分析了1115例连续接受三种可用IFNβ制剂之一治疗的MS患者,平均治疗40个月(1 - 120个月),采用MxA蛋白诱导试验检测NAb的存在情况。总体而言,32%的患者NAb呈阳性,中和滴度高于10。接受Avonex治疗的患者中NAb的频率,即血清阳性率为13%,Betaferon为43%,Rebif22为39%,Rebif44为30%。此外,观察到不同制剂诱导高滴度水平的潜力,即免疫原性存在差异。Avonex的血清阳性率最低,其免疫原性也较低,通常诱导的滴度较低。Betaferon在诱导NAb时血清阳性率最高,但与Rebif22和Rebif44相比,诱导的滴度较低。超过五年的治疗持续时间与血清阳性率和滴度水平的降低仅存在微弱关联。总之,临床环境中针对IFNβ的NAb很常见,且IFNβ制剂不仅在NAb血清阳性率上存在差异,在免疫原性上也有所不同。