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首页> 外文期刊>Journal of neurology >Optimising MS disease-modifying therapies: antibodies in perspective.
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Optimising MS disease-modifying therapies: antibodies in perspective.

机译：优化MS疾病缓解疗法：抗体的观点。

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A proportion of people with multiple sclerosis (MS) treated with interferon (IFN) a develop neutralising anti-IFN beta antibodies (NABs). The immunogenicity of the available commercial compounds relates to the genetic structure of the IFN beta molecule, its mode of production, glycosylation status, aggregate formation, commercial formulation, potency, dose, frequency and, possibly, route of administration. At present, it is not possible to predict who will develop NABs usually appear within the first 2 years of starting therapy. In patients treated with IFN beta in whom NABs persist for a significant period of time, their presence is associated with a reduction in both the biological effects and clinical efficacy. Approximately one third of NAB-positive patients with a titre > 20 NU/mL will revert to NAB-negative status with long-term follow-up. The persistence of NABs appears to be linked to the type of IFN beta treatment as well as the titre of antibodies. The overall efficacy of IFN beta and, hence,of any biological disease-modifying treatment (DMT) would be substantially improved if the development of NABs could be prevented or reversed. Although the overall efficacy of IFN beta in MS is relatively modest, the efficacy in individuals who remain NAB-negative is considerably better than in those who become persistently NAB-positive. One could argue that when comparing the 'true' clinical efficacy of different IFN beta products, the comparisons should be limited to the cohorts that remain NAB-negative. As a corollary, the therapeutic efficacy of IFN beta could be maximised if patients who tolerate higher-dose preparations could be prevented from developing persistent NABs. Strategies employed to prevent or reverse the development of NABs with other biological compounds (e. g. insulin, factor VIII, IFN beta, recombinant human erythropoietin) include improvements in the manufacturing process, immunosuppression, induction of tolerance and deimmunisation, and these should be considered in relation to biological DMT therapy as part of future clinical studies.
机译：一部分接受干扰素（IFN）治疗的多发性硬化症（MS）患者会产生中和性抗IFNβ抗体（NABs）。可获得的市售化合物的免疫原性涉及IFNβ分子的遗传结构，其生产方式，糖基化状态，聚集体形成，市售制剂，效价，剂量，频率以及可能的给药途径。目前，尚无法预测谁会在开始治疗的最初2年内出现NAB。在NAB持续时间很长的接受IFNβ治疗的患者中，其存在与生物学效应和临床功效的降低相关。滴度> 20 NU / mL的NAB阳性患者中约有三分之一将通过长期随访恢复为NAB阴性。 NAB的持久性似乎与IFNβ治疗的类型以及抗体的效价有关。如果可以预防或逆转NAB的发生，则IFNβ的总体功效以及任何生物疾病缓解疗法（DMT）的总体功效将得到显着改善。尽管IFNβ在MS中的总体疗效相对中等，但对于NAB阴性的患者，其疗效要比NAB阳性的患者好得多。有人可能会争辩说，当比较不同IFNβ产品的“真实”临床疗效时，比较应仅限于NAB阴性的人群。推论是，如果可以阻止耐受高剂量制剂的患者持续产生NAB，则可以最大程度地提高IFNβ的治疗效果。预防或逆转NAB与其他生物化合物（例如胰岛素，因子VIII，IFNβ，重组人促红细胞生成素）的发展所采用的策略包括制造工艺的改进，免疫抑制，诱导耐受性和解除免疫性，应将这些因素综合考虑生物DMT治疗作为未来临床研究的一部分。

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