Cagnoni Pablo J
University of Colorado Cancer Center, Denver, Colorado, USA.
J Antimicrob Chemother. 2002 Feb;49 Suppl 1:81-6. doi: 10.1093/jac/49.suppl_1.81.
Liposomal amphotercin B was compared with conventional amphotericin B for empirical antifungal therapy in febrile neutropenic patients in a randomized, double-blind, multicentre trial. Using a composite end-point, the two drugs were equivalent in overall efficacy. However, the liposomal amphotericin B treatment group had fewer proven fungal infections, fewer infusion-related side effects and less nephrotoxicity. Patient data from that study were analysed to compare the pharmacoeconomics of liposomal versus conventional amphotericin B therapy. Itemized billing data from 414 patients were collected and analysed. Hospital costs from first dose were significantly higher for all patients who received liposomal amphotericin B ($48,962 versus $43,183, P = 0.02). However, hospital costs were very sensitive to the cost of the study medication ($39,648 versus $43,048, when acquisition costs are not included, P = 0.4). Using decision analysis models and sensitivity analyses to vary the cost of study medications and risk of nephrotoxicity, the break-even points for the cost of liposomal therapy were calculated to range from $72 to $87 per 50 mg for all patients, and $83 to $112 per 50 mg in allogeneic bone marrow transplant patients. Therefore, the drug acquisition costs and the risk of nephrotoxicity are important factors in determining the cost-effectiveness of liposomal amphotericin B as empirical therapy in persistently febrile neutropenic patients. In a recent randomized double-blind study comparing liposomal amphotericin B at 3 or 5 mg/kg/day with amphotericin B lipid complex (ABLC) 5 mg/kg/day as empirical antifungal treatment in patients with febrile neutropenia, liposomal amphotericin B was associated with less toxicity than ABLC, both in terms of infusion-related reactions and nephrotoxicity. The incidence of study drug discontinuation due to toxicity was: liposomal amphotericin B 3 mg/kg/day, 14%; liposomal amphotericin B 5 mg/kg/day, 15%; and ABLC, 42% (P < 0.001).
在一项随机、双盲、多中心试验中，对发热性中性粒细胞减少患者进行经验性抗真菌治疗时，将脂质体两性霉素B与传统两性霉素B进行了比较。使用复合终点指标，两种药物的总体疗效相当。然而，脂质体两性霉素B治疗组确诊的真菌感染较少，输液相关副作用较少，肾毒性也较小。对该研究的患者数据进行分析，以比较脂质体两性霉素B与传统两性霉素B治疗的药物经济学。收集并分析了414例患者的分项计费数据。所有接受脂质体两性霉素B治疗的患者从首剂开始的住院费用显著更高（48,962美元对43,183美元，P = 0.02）。然而，住院费用对研究药物的成本非常敏感（不包括购置成本时为39,648美元对43,048美元，P = 0.4）。使用决策分析模型和敏感性分析来改变研究药物的成本和肾毒性风险，计算出所有患者脂质体治疗成本的盈亏平衡点为每50毫克72至87美元，异基因骨髓移植患者为每50毫克83至112美元。因此，药物购置成本和肾毒性风险是决定脂质体两性霉素B作为持续性发热性中性粒细胞减少患者经验性治疗的成本效益的重要因素。在最近一项随机双盲研究中，将3或5毫克/千克/天的脂质体两性霉素B与5毫克/千克/天的两性霉素B脂质复合物（ABLC）作为发热性中性粒细胞减少患者的经验性抗真菌治疗进行比较，脂质体两性霉素B在输液相关反应和肾毒性方面的毒性均低于ABLC。因毒性而停用研究药物的发生率为：3毫克/千克/天的脂质体两性霉素B为14%；5毫克/千克/天的脂质体两性霉素B为15%；ABLC为42%（P < 0.001）。
