Posaconazole vs fluconazole/itraconazole in the prophylaxis of invasive fungal infections in immunocompromised patients: A cost-effectiveness analysis in Greece

Abstract

Background:

Invasive fungal infections (IFIs) present a major issue in clinical practice, due to their high morbidity and mortality rates. In a pivotal multi-centre, randomized clinical trial, posaconazole prophylaxis prevented IFIs more effectively than did either fluconazole or itraconazole, and improved overall survival.

Objective:

The aim of this study was to perform an economic evaluation of the aforementioned therapeutic strategies for IFI prophylaxis in neutropenic patients, in the Greek healthcare setting.

Method:

A decision analytic model was developed, which described the course of neutropenic patients under posaconazole or standard azole (fluconazole or itraconazole) treatment. Effectiveness data for each treatment regimen were derived from published results of a pivotal, multi-centre, randomized clinical trial. Cost and healthcare resources utilization data depict Greek clinical practice and are derived from official Greek sources, from a third party payer perspective.

Results:

Prophylaxis with posaconazole resulted in fewer IFIs (0.05 vs 0.11 per patient) compared to treatment with fluconazole or itraconazole, during the first 100 days from initiation of prophylaxis treatment. The cost per avoided IFI with posaconazole was €6455, while the incremental cost per life year gained (LYG) was estimated at €24,196. Extensive sensitivity analyses corroborated the base-case results. Possible limitations of the study are the exclusion of indirect and outpatient costs from the analysis and the inherent uncertainty with regards to the transferability of the clinical efficacy results of the clinical trial to the Greek healthcare setting.

Conclusions:

The utilization of posaconazole for prophylaxis of IFIs neutropenic patients is a therapeutic strategy that provides superior clinical efficacy, while being cost-effective compared to alternative therapies.     

伊曲康唑对合用药物药代动力学的影响机制初探

目的探讨伊曲康唑对合用药物药代动力学的影响机制,为临床上安全合理地利用合成药物提供依据。方法利用健康成人的肝细胞微粒体,将其分为加入不同浓度伊曲康唑的10个小组,浓度梯度为0.0、0.4、0.8、1.6、3.2μg/ml,每组做5个平行组,之后在其中五组加入肝细胞微粒体细胞色素的P450的同功酶1A2的底物非那西丁,在另外五组中加入同工酶3A4的底物睾酮,测量不同伊曲康唑下的同功酶1A2和3A4的相对活性。结果各浓度伊曲康唑组对同功酶1A2作用效果无明显差异,各浓度伊曲康唑组对同功酶3A4的作用较明显,同功酶3A4的活性随着伊曲康唑的浓度增大而减小,其减小到本实验的最大活性一半时的伊曲康唑的浓度为0.7μg/ml。结论伊曲康唑对健康成年人肝细胞微粒体细胞色素酶同功酶1A2的活性无显著影响;但是它对同功酶3A4的活性有明显抑制作用,极大地影响了同功酶3A4对合用药物药代动力学的各种参数。     

伊曲康唑注射液治疗ICU侵袭性真菌感染的疗效与安全性

目的观察探讨伊曲康唑注射液治疗ICU侵袭性真菌感染（IFI）的疗效与安全性,总结其临床应用价值。方法选取我院2010年6月至2012年6月ICU中发生IFI的患者46例,按照数字表随机抽取法将其分成两组,各为23例,观察组使用伊曲康唑注射液治疗,对照组使用氟康唑治疗,观察两组临床疗效和治疗期间药物不良反应。结果观察组治疗28d后疗效总有效率为100.0%（23/23）,真菌清除率为91.3%（21/23）,治疗期间不良反应率为8.7%（2/23）;对照组治疗28d后疗效总有效率为73.9%（17/23）,真菌清除率为65.2%（15/23）,治疗期间不良反应率为26.1%（6/23）,两组疗效、真菌清除率及药物不良反应率比较差异显著（P〈0.05）,具有统计学意义。结论伊曲康唑注射液治疗ICU侵袭性真菌感染（IFI）的疗效确切,显著优于使用氟康唑治疗,可加快真菌清除,尽快缓解临床症状,药物不良反应少,安全可靠,值得临床合理推广。