泊沙康唑预防血液恶性肿瘤患者侵袭性真菌感染的快速卫生技术评估

Posaconazole as Prophylaxis for Invasive Fungal Infections among the Patients with Hematological Malignancies: A Rapid Health Technology Assessment

目的:通过快速卫生技术评估,对泊沙康唑预防血液恶性肿瘤患者侵袭性真菌感染(IFIs)的有效性、安全性、经济性进行评价,为临床实践与决策者提供最新的循证依据。方法:检索各大卫生技术评估(HTA)网站及PubMed、the Cochrane Library、CNKI、万方数据、VIP等国内外文献数据库,仅纳入泊沙康唑预防IFIs的系统评价、Meta分析、HTA和药物经济学研究,由2名评价者独立筛选文献及提取数据结果,并对结果进行综合分析。结果:共纳入34篇文献,其中14篇为系统评价/Meta分析,19篇为药物经济学研究,1篇为系统评价/Meta分析合并药物经济学研究。有效性评价显示泊沙康唑可减少血液恶性肿瘤患者IFIs发生率,显著优于氟康唑和伊曲康唑,尤其是急性髓细胞白血病和骨髓增生异常综合征患者,预防侵袭性曲霉菌感染优于氟康唑和伊曲康唑,预防侵袭性念珠菌感染差异无统计学意义;显著降低全因死亡率和感染相关死亡率。安全性评价显示泊沙康唑与其他抗真菌药物相比不良反应发生率无显著差异。经济性评价显示仅一项研究示急性髓细胞白血病第1次巩固化疗后使用氟康唑预防IFIs更具经济性,其余研究均显示在意愿支付阈值内泊沙康唑更具成本-效果优势。结论:泊沙康唑预防血液恶性肿瘤患者IFIs有较好的有效性、安全性和经济性,有必要开展更多泊沙康唑缓释片/注射剂安全性、有效性的头对头研究及经济学研究。

Objective:To evaluate the efficacy, safety and cost-effectiveness of posaconazole as prophylaxis for invasive fungal infections(IFIs) among the patients with hematological malignancies in rapid health technology assessment, so as to provide currently available best evidence for health providers and decision makers. Methods:Systematic review(SR), Meta-analysis, health techndogy assessment(HTA) and pharmacoeconomic researches regarding prophylaxis for IFIs treated by posaconazole were searched in the website of HTA and databases such as PubMed, the Cochrane Library, CNKI, WanFang Data, VIP. After independent study selection, data extraction and quality assessment, included studies were comprehensively analyzed as appropriate. Results:A total of 15 SR/Meta analyses and 19 cost-effectiveness evaluations were finally included. This study showed that posaconazole was a good alternative option for the prophylaxis for IFIs. Compared with fluconazole and itraconazole, posaconazole was dominantly effective in preventing IFIs among immunocompromised patients, particularly those with acute myeloid leukaemia and myelodysplastic syndrome. Posaconazole was superior to fluconazole and itraconazole in preventing invasive aspergillus infections, but showed no significance in preventing invasive candida infections. Posaconazole significantly reduced all-cause deaths and IFI-related mortality, despite no difference in reducing the risk of adverse events compared with other antifungal agents. Pharmacoeconomic studies showed that compared with other antifungal treatment options, posaconazole was a cost-effective prophylaxis treatment for IFIs under the willingness-to-pay threshold in different settings. Conclusion: Posaconazole is effective, safe and cost-effective for the prophylaxis treatment of IFIs in patients with hematological malignancies. More head-to-head studies among efficacy/safety and pharmacoeconomic studies focusing on posaconazole delayed-release tablets or injections are needed to provide more evidence to be conducted.