一项对接受中国个体化递增低剂量预防治疗（CHIPS）方案 4 年预防治疗的严重甲型血友病男孩进行的长期结局分析。

A long term outcomes analysis of severe haemophilia A boys receiving 4 years prophylaxis on the Chinese Haemophilia Individualized escalating low dose Prophylaxis (CHIPS).

机构信息

Hematology Department, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China.

Haemophilia Diagnosis and Treatment Center, Department of Hematology and Oncology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

出版信息

Thromb Res. 2024 Sep;241:109110. doi: 10.1016/j.thromres.2024.109110. Epub 2024 Aug 7.

DOI:10.1016/j.thromres.2024.109110

PMID:39116483

Abstract

BACKGROUND

The Chinese Haemophilia Individualized Prophylaxis Study (CHIPS), which was launched in 2016, reported a significant reduction in haemarthrosis over a one-year study. However, its long-term efficacy requires verification. This paper summarizes the clinical outcomes of 18 severe haemophilia A (SHA) patients who completed one year on the CHIPS and 3 more years of follow-up.

METHODS

Clinical follow-up was based on the CHIPS protocol (from July 2018 to July 2021). Escalation was based on index joint bleeding, and serial ultrasound (greyscale and colour Doppler) examinations of the index joints (both sides of the ankles, knees and elbows) were conducted every 6 months via a scoring system.

RESULTS

A total of 18 SHA patients completed the 3-year study. Fifteen patients dropped out due to the financial crisis during the COVID-19 pandemic in China. The median age was 5.4 (range 4.3-6.9) years. A significant reduction in haemarthrosis was achieved, with mean annual bleeding rates reduced from 18.9 ± 2.8 to 1.7 ± 0.4 (p < 0.001), annual joint bleeding rates from 3.1 ± 0.7 to1.2 ± 0.3 (p < 0.028). 5 out of 8 target joint resolved. Sixteen doses were escalated. At study exit, the heterogeneous treatment outcomes of the SHA boys were 5 at step 4 (20-25 lU/kg, every other day), 10 at step 3 (15-20 IU/kg, 3×/week), 2 at step 2 (10-15 lU/kg, 3×/week) and 1 at step 1 (10-15 lU/kg, 2×/week). The mean FVIII consumption was 2964 IU/kg/year, with savings. The quality of life improved, with Canadian Haemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT, Chinese Version 2.0) scores ranging from 68.8 to 78.8. There was no change in the ultrasound score.

CONCLUSION

Our follow-up data on the 18 SHA boys after completing one year on the CHIPS verify the long-term efficacy of the CHIPS for haemarthrosis reduction, joint health preservation, improvement in the quality of life of the boys and cost savings.

摘要

背景

中国血友病个体化预防治疗研究（CHIPS）于 2016 年启动，该研究在为期一年的研究中报告了关节出血显著减少。然而，其长期疗效仍需验证。本文总结了 18 例重度血友病 A（SHA）患者完成 CHIPS 治疗 1 年后，再进行 3 年随访的临床结果。

方法

临床随访基于 CHIPS 方案（2018 年 7 月至 2021 年 7 月）。根据指标关节出血情况进行药物剂量升级，每隔 6 个月对双侧踝关节、膝关节和肘关节进行一次关节超声（灰阶和彩色多普勒）检查，并采用评分系统进行评估。

结果

共 18 例 SHA 患者完成了 3 年的研究。15 例患者因中国 COVID-19 大流行期间的经济危机而中途退出。中位年龄为 5.4（4.3-6.9）岁。关节出血显著减少，平均年出血率从 18.9±2.8 降至 1.7±0.4（p<0.001），年关节出血率从 3.1±0.7 降至 1.2±0.3（p<0.028）。8 个目标关节中有 5 个得到缓解。16 例患者增加了药物剂量。研究结束时，18 例 SHA 男孩的治疗结果分别为：5 例处于第 4 阶段（20-25 IU/kg，隔日一次），10 例处于第 3 阶段（15-20 IU/kg，每周 3 次），2 例处于第 2 阶段（10-15 IU/kg，每周 3 次），1 例处于第 1 阶段（10-15 IU/kg，每周 2 次）。FVIII 的平均年消耗量为 2964 IU/kg，节省了费用。生活质量提高，加拿大血友病患儿生活质量评估工具（CHO-KLAT，中文版 2.0）评分从 68.8 分升至 78.8 分。超声评分无变化。