在3期XTEND-1和XTEND-Kids研究中，使用艾美赛珠单抗α对甲型血友病患者进行围手术期管理。

Perioperative Management With Efanesoctocog Alfa in Patients With Haemophilia A in the Phase 3 XTEND-1 and XTEND-Kids Studies.

作者信息

Klamroth Robert, von Drygalski Annette, Hermans Cedric, Park Young-Shil, Chan Anthony K C, Kupesiz Alphan, Alvarez-Román María Teresa, Malec Lynn, Santagostino Elena, Neill Graham, Bystrická Linda, Dumont Jennifer, Abad-Franch Lydia, Fetita Lila-Sabrina, Khoo Liane

机构信息

Vivantes Klinikum, Friedrichshain, Berlin, and Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Medical Faculty, University of Bonn, Bonn, Germany.

Department of Medicine, Division of Hematology/Oncology, University of California San Diego, San Diego, California, USA.

出版信息

Haemophilia. 2025 May;31(3):391-400. doi: 10.1111/hae.70017. Epub 2025 Mar 18.

DOI:10.1111/hae.70017

PMID:40099428

Abstract

INTRODUCTION

The Phase 3 studies, XTEND-1 (NCT04161495) and XTEND-Kids (NCT04759131), showed once-weekly efanesoctocog alfa provided high-sustained factor VIII (FVIII) activity levels that translated into highly effective bleed prevention in patients with severe haemophilia A.

AIM

This analysis evaluated the efficacy and safety of efanesoctocog alfa for perioperative management during XTEND-1 and XTEND-Kids.

METHODS

Patients undergoing major or minor surgery were to receive a single preoperative 50 IU/kg dose, with additional 30 or 50 IU/kg doses every 2-3 days as needed following major surgery. Outcomes assessed included FVIII activity levels, number and dose of efanesoctocog alfa injections, surgeon's/investigator's assessment of haemostatic response, total factor consumption, estimated blood loss, number and type of blood transfusions, and safety.

RESULTS

In XTEND-1, 11 adults/adolescents underwent 12 evaluable major surgeries (6 orthopaedic). Eleven surgeries had one preoperative dose (median [range]: 49.9 [13-52] IU/kg); one had no preoperative dose. Median (range) total consumption from Day -1 to 14 was 163.3 (45-361) IU/kg. In XTEND-Kids, two children underwent major surgery with a single preoperative loading dose (60.4 and 61.9 IU/kg). Across trials, 15 adults/adolescents underwent 18 minor surgeries and 8 children underwent 9 minor surgeries, with a single preoperative dose or no preoperative dose (5 surgeries in adults/adolescents). Haemostatic response was rated excellent for all surgeries. No surgeries required blood transfusion. No safety concerns or inhibitor development was reported.

CONCLUSION

Efanesoctocog alfa provided highly effective perioperative protection in patients with severe haemophilia A.

TRIAL REGISTRATION

XTEND-1: NCT04161495 https://clinicaltrials.gov/study/NCT04161495; XTEND-Kids: NCT04759131 https://clinicaltrials.gov/study/NCT04759131.

摘要

引言

3期研究XTEND-1（NCT04161495）和XTEND-Kids（NCT04759131）表明，每周一次的依诺凝血因子α可提供持续的高因子VIII（FVIII）活性水平，这转化为对重度A型血友病患者的高度有效的出血预防。

目的

本分析评估了依诺凝血因子α在XTEND-1和XTEND-Kids研究中围手术期管理的疗效和安全性。

方法

接受大手术或小手术的患者术前接受一次50IU/kg的剂量，大手术后根据需要每2-3天额外给予30或50IU/kg的剂量。评估的结果包括FVIII活性水平、依诺凝血因子α注射的次数和剂量、外科医生/研究者对止血反应的评估、总凝血因子消耗量、估计失血量、输血的次数和类型以及安全性。

结果

在XTEND-1研究中，11名成人/青少年接受了12例可评估的大手术（6例骨科手术）。11例手术术前接受了一次剂量（中位数[范围]：49.9[13-52]IU/kg）；1例未接受术前剂量。从第-1天到第14天的总消耗量中位数（范围）为163.3（45-361）IU/kg。在XTEND-Kids研究中，2名儿童接受了大手术，术前单次负荷剂量分别为60.4和61.9IU/kg。在各项试验中，15名成人/青少年接受了18例小手术，8名儿童接受了9例小手术，术前接受了单次剂量或未接受术前剂量（成人/青少年中有5例手术）。所有手术的止血反应均被评为优秀。所有手术均无需输血。未报告安全问题或抑制剂产生。