人重组DNA衍生的抗血友病因子（凝血因子VIII）治疗甲型血友病。重组凝血因子VIII研究组。

Human recombinant DNA-derived antihemophilic factor (factor VIII) in the treatment of hemophilia A. recombinant Factor VIII Study Group.

作者信息

Schwartz R S, Abildgaard C F, Aledort L M, Arkin S, Bloom A L, Brackmann H H, Brettler D B, Fukui H, Hilgartner M W, Inwood M J

机构信息

Cutter Biological, Miles Inc., Berkeley, Calif. 94701.

出版信息

N Engl J Med. 1990 Dec 27;323(26):1800-5. doi: 10.1056/NEJM199012273232604.

DOI:10.1056/NEJM199012273232604

PMID:2123300

Abstract

BACKGROUND

Current treatment of hemophilia A, a hereditary disorder affecting approximately 1 in 10,000 males, relies on plasma-derived factor VIII concentrates. We tested the safety and efficacy of a recombinant factor VIII preparation for the treatment of this disorder.

METHODS

We conducted the investigation in three stages: comparing the pharmacokinetics of plasma-derived and recombinant factor VIII, assessing the efficacy of recombinant factor VIII for home therapy, and assessing its efficacy for major surgical procedures and hemorrhage. A total of 107 subjects with hemophilia, 20 of whom had not been treated previously, enrolled in the investigation.

RESULTS

The in vivo recovery and elimination half-lives of recombinant factor VIII equaled or exceeded those of plasma-derived factor VIII. Seventy-six subjects participated in a home-treatment program, using recombinant factor VIII for 69 to 807 days (median, 618); home diaries of 56 subjects treated for 5 months were analyzed. Of 540 bleeding episodes, 399 (73.9 percent) required only one treatment with recombinant factor VIII. The projected annual consumption of recombinant factor VIII was similar to that of plasma-derived factor VIII concentrate. Twenty-six subjects received recombinant factor VIII for 22 surgical procedures and 10 serious hemorrhages; hemostasis was excellent in all cases. De novo formation of inhibitors occurred in only 1 of 85 previously treated subjects. Inhibitor antibodies also developed in 6 of 21 children, 20 of whom had not previously been treated; 5 had low levels (less than or equal to 7.5 Bethesda units) despite continued treatment with recombinant factor VIII. There was no evidence of new formation of antibody to foreign proteins, and recombinant factor VIII was well tolerated.

CONCLUSIONS

Recombinant factor VIII has biologic activity comparable to that of plasma factor VIII and is safe and efficacious for the treatment of hemophilia A.

摘要

背景

甲型血友病是一种遗传性疾病，约每10000名男性中有1人患病，目前的治疗依赖于血浆源性凝血因子VIII浓缩物。我们测试了一种重组凝血因子VIII制剂治疗该疾病的安全性和有效性。

方法

我们分三个阶段进行研究：比较血浆源性和重组凝血因子VIII的药代动力学，评估重组凝血因子VIII在家治疗中的疗效，以及评估其在重大外科手术和出血治疗中的疗效。共有107名血友病患者参加了这项研究，其中20人此前未接受过治疗。

结果

重组凝血因子VIII的体内回收率和消除半衰期等于或超过血浆源性凝血因子VIII。76名受试者参与了家庭治疗计划，使用重组凝血因子VIII治疗69至807天（中位数为618天）；分析了56名接受治疗5个月的受试者的家庭日记。在540次出血事件中，399次（73.9%）仅需用重组凝血因子VIII治疗一次。重组凝血因子VIII的预计年消耗量与血浆源性凝血因子VIII浓缩物相似。26名受试者接受重组凝血因子VIII进行了22次外科手术和10次严重出血治疗；所有病例止血效果均极佳。在85名先前接受过治疗的受试者中，仅1人出现了抑制剂的重新形成。21名儿童中有6人也产生了抑制剂抗体，其中20人此前未接受过治疗；尽管继续使用重组凝血因子VIII治疗，但5人的抗体水平较低（小于或等于7.5贝塞斯达单位）。没有证据表明对外源蛋白形成了新的抗体，重组凝血因子VIII耐受性良好。