Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.
Haemophilia. 2014 May;20 Suppl 4:23-8. doi: 10.1111/hae.12428.
Currently, new clotting factor concentrates are becoming available or are in advanced clinical studies that will significantly improve the treatment of patients with Haemophilia A or Haemophilia B. Various technologies are applied to extend half-life and/or allow for alternative routes of administration, e.g. subcutaneous route. Today, the advances for recombinant factor IX are significantly with half-life extensions to up to 100 h, allowing substitution intervals of 1-2 weeks. For recombinant factor VIII (FVIII) products the effect so far is only moderate, as the half-life extension is limited to about 15-18 h by the clearance of FVIII through its binding to von Willebrand factor. However, novel products applying new technologies with significantly extended half-life are already at the horizont, as a bispecific antibody that mimics FVIII. The pharmacokinetic improvements of the new products will lead to a revision of our current treatment regimens, with regard to intended trough levels, number of tolerated bleeds and likely will drive a greater individualization of regimens. Clearly, the potential of anti drug antibody response for these modified proteins must not be higher than with our current products. Another challenge are the increasingly diverse biochemical characteristics of the new products, that have to be considered when determining potencies and also when monitoring treatment in patients with the various available assays. Despite these challenges, the new products will significantly improve treatment and quality of life for our patients with haemophilia.
目前，新型凝血因子浓缩物正在研发或处于临床研究的后期阶段，这将显著改善 A 型或 B 型血友病患者的治疗效果。各种技术被应用于延长半衰期和/或允许替代给药途径，例如皮下途径。如今，重组因子 IX 的进展显著，半衰期延长至 100 小时，允许替代间隔 1-2 周。对于重组因子 VIII (FVIII) 产品，迄今为止效果仅为中等，因为 FVIII 通过与 von Willebrand 因子结合而清除，半衰期延长仅限制在 15-18 小时左右。然而，应用新技术并具有显著延长半衰期的新型产品已经在研发中，例如模拟 FVIII 的双特异性抗体。新产品的药代动力学改善将导致我们当前治疗方案的修订，涉及预期的谷浓度、耐受出血的次数，并可能推动治疗方案的个体化。显然，对于这些改良蛋白，抗药物抗体反应的潜在风险不能高于我们目前的产品。另一个挑战是新型产品日益多样化的生化特性，在确定效价和监测各种可用检测方法下患者的治疗时，都必须考虑这些特性。尽管存在这些挑战，但新型产品将显著改善我们的血友病患者的治疗效果和生活质量。
