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单剂量 rasburicase 在预防和治疗成人肿瘤细胞溶解综合征中的疗效和成本:一项荟萃分析。

Efficacy and cost of single-dose rasburicase in prevention and treatment of adult tumour lysis syndrome: a meta-analysis.

机构信息

Department of Clinical and Administrative Sciences, California Northstate University College of Pharmacy, Rancho Cordova, CA 95670, USA.

出版信息

J Clin Pharm Ther. 2013 Aug;38(4):301-8. doi: 10.1111/jcpt.12061. Epub 2013 Apr 3.

Abstract

WHAT IS KNOWN AND OBJECTIVE

Single-dose rasburicase for the treatment and prevention of hyperuricaemia in adult and paediatric patients with cancer at high risk of tumour lysis syndrome (TLS) has been widely adopted in pharmacy practice as unlabelled use with limited clinical evidence. This meta-analysis study evaluated the efficacy and cost savings of a single-dose rasburicase (SDR) regimen compared with the Food and Drug Administration-approved daily dosing of rasburicase (DDR) for 5 days or the traditional treatment with allopurinol in adult cancer patients with hyperuricaemia or at high risk for TLS.

METHODS

Prospective and retrospective studies were retrieved from a systemic search of major electronic data sources. Studies included in the meta-analysis were those with SDR for the prophylaxis of high-risk TLS or treatment of hyperuricaemia in adult patients with cancer. The results of response rate and controlling of time-dependent plasma uric acid (UA) reduction were pooled and compared with the results from patients treated with DDR for 5 days or patients treated with allopurinol. A cost analysis was performed to analyse the treatment costs for adults with hyperuricaemia or at high risk for TLS.

RESULTS AND DISCUSSION

Ten studies (eight retrospective and two prospective) evaluated the SDR response rate and plasma UA level reduction over time. The pooled total number of patients treated with SDR (from 0·05 mg/kg to 0·20 mg/kg) was 269. The pooled response rate of the SDR arm was not significantly different than that of DDR (0·2 mg/kg) arm (88·15% vs. 90·18%, P = 0·542), but significantly stronger than that of allopurinol (300 mg/day orally days 1 to 5) arm (response rate: 88·15% vs. 66%, P < 0·0005). Pooled SDR group efficiently controlled the plasma uric acid (UA) level below 4·5 mg/dL over 24 h, 48 h and 72 h, whereas DDR reduced plasma UA levels to hypouricaemia level (<2 mg/dl). In addition, cost analysis demonstrated that standard-dose SDR (≥6 mg) has non-inferior clinical benefit and significant cost savings compared with the DDR regimen.

WHAT IS NEW AND CONCLUSION

Single-dose rasburicase (SDR) for adult cancer patients with hyperuricaemia or at high risk for TLS demonstrated better response rate and stronger control of uric acid level compared with allopurinol. SDR response rate was not inferior to that of DDR, and the standard-dose SDR generates more cost savings compared with the DDR. It suggests that the single-dose rasburicase is clinically effective and cost efficient for the prophylaxis of high-risk TLS and the treatment of hyperuricaemia in adult patients with cancer. Additional randomized control studies are needed to confirm the findings of this meta-analysis study.

摘要

已知和目的

单剂量拉布立酶用于治疗和预防高肿瘤溶解综合征 (TLS) 风险的成年和儿科癌症患者的高尿酸血症,已作为无标签用途在药学实践中广泛采用,临床证据有限。本荟萃分析研究评估了与拉布立酶的美国食品和药物管理局批准的 5 天每日剂量(DDR)或传统的别嘌醇治疗相比,单剂量拉布立酶(SDR)方案治疗成年癌症患者高尿酸血症或高 TLS 风险的疗效和成本节约。

方法

从主要电子数据库的系统检索中检索前瞻性和回顾性研究。荟萃分析中包括用于预防高危 TLS 或治疗成年癌症患者高尿酸血症的 SDR 方案。汇集反应率和控制时间依赖性血浆尿酸(UA)降低的结果,并与接受 DDR 治疗 5 天的患者或接受别嘌醇治疗的患者的结果进行比较。进行成本分析以分析高尿酸血症或高 TLS 风险的成年患者的治疗成本。

结果与讨论

十项研究(八项回顾性和两项前瞻性)评估了 SDR 反应率和随时间推移的血浆 UA 水平降低。SDR 治疗(0.05mg/kg 至 0.20mg/kg)的汇总患者总数为 269 例。SDR 组的反应率与 DDR(0.2mg/kg)组无显著差异(88.15%比 90.18%,P=0.542),但明显强于别嘌醇(300mg/天口服第 1 至 5 天)组(反应率:88.15%比 66%,P<0.0005)。SDR 组可有效控制 24 小时、48 小时和 72 小时内的血浆尿酸(UA)水平低于 4.5mg/dL,而 DDR 则将血浆 UA 水平降低至低尿酸血症水平(<2mg/dl)。此外,成本分析表明,标准剂量 SDR(≥6mg)与 DDR 方案相比,具有非劣效的临床获益和显著的成本节约。

新发现和结论

对于高尿酸血症或高 TLS 风险的成年癌症患者,单剂量拉布立酶(SDR)显示出更好的反应率和更强的尿酸水平控制能力,与别嘌醇相比。SDR 反应率不低于 DDR,标准剂量 SDR 与 DDR 相比可节省更多成本。这表明单剂量拉布立酶在预防高危 TLS 和治疗成年癌症患者高尿酸血症方面具有临床疗效和成本效益。需要进一步的随机对照研究来证实本荟萃分析研究的结果。

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