Gneiss C, Tripp P, Reichartseder F, Egg R, Ehling R, Lutterotti A, Khalil M, Kuenz B, Mayringer I, Reindl M, Berger T, Deisenhammer F
Clinical Department of Neurology, Innsbruck Medical University, 6020 Innsbruck, Austria.
Mult Scler. 2006 Dec;12(6):731-7. doi: 10.1177/1352458506070941.
Interferon beta (IFNbeta) is a first-line therapy for multiple sclerosis (MS). However, some patients experience a decline in efficacy with continued therapy due to the development of anti-IFNbeta neutralizing antibodies (NAb). We investigated the frequency of NAb cross-sectionally in 846 MS patients who were receiving IFNbeta-1b, IFNbeta-1a im, or IFNbeta-1a sc. The frequency of NAb in patients receiving IFNbeta-1a im was lower (5%) than in patients treated with any other form of IFNbeta (22-35%) (P < 0.0001). Binding antibodies (BAb) were measured in 808 patients. The frequency differed significantly between treatment groups, ranging from 45% (IFNbeta-1a im) to 88% (IFNbeta-1b). The proportion of NAb-positive patients within the BAb-positive group differed significantly among treatment groups, ranging between 12% (IFNbeta-1a im) and 51% (IFNbeta-1a sc). The median NAb titer from all IFNbeta-1a-treated patients was higher than from IFNbeta-1b-treated patients (446 versus 171 NU/ mL, P = 0.04). Among NAb-positive patients, the frequency of NAb titers > 100 NU/mL was 71% for IFNbeta-1a compared with 58% for IFNbeta-1b (P = 0.04). Except for conflicting data regarding IFNbeta-1a sc, the results are generally consistent with the literature and together with the differing proportion of NAb-positive patients within the BAb-positive group, provide further insight into the immunogenicity of the IFNbeta preparations.
干扰素β（IFNβ）是治疗多发性硬化症（MS）的一线药物。然而，由于抗IFNβ中和抗体（NAb）的产生，一些患者在持续治疗过程中疗效会下降。我们对846例接受IFNβ-1b、肌肉注射IFNβ-1a或皮下注射IFNβ-1a治疗的MS患者进行了NAb的横断面频率调查。接受肌肉注射IFNβ-1a的患者中NAb的频率（5%）低于接受任何其他形式IFNβ治疗的患者（22%-35%）（P<0.0001）。在808例患者中检测了结合抗体（BAb）。各治疗组之间的频率差异显著，范围从45%（肌肉注射IFNβ-1a）到88%（IFNβ-1b）。BAb阳性组中NAb阳性患者的比例在各治疗组之间差异显著，范围在12%（肌肉注射IFNβ-1a）至51%（皮下注射IFNβ-1a）之间。所有接受IFNβ-1a治疗患者的NAb中位滴度高于接受IFNβ-1b治疗的患者（446对171 NU/mL，P=0.04）。在NAb阳性患者中，IFNβ-1a的NAb滴度>100 NU/mL的频率为71%，而IFNβ-1b为58%（P=0.04）。除了关于皮下注射IFNβ-1a的数据存在矛盾外，这些结果总体上与文献一致，并且结合BAb阳性组中NAb阳性患者的不同比例，进一步深入了解了IFNβ制剂的免疫原性。
