Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: An externally controlled trial
Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: An externally controlled trial
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DOI：
10.1086/508774
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发表时间：
2007-01-01
影响因子：
11.8
通讯作者：
Perfect, John R.
中科院分区：
文献类型：
--
作者：
Walsh, Thomas J.;Raad, Issam;Perfect, John R.
背景资料。侵袭性曲霉病是免疫功能低下患者发病和死亡的重要原因。目前的治疗方法提供的好处有限。泊沙康唑是一种广谱三唑类化合物，具有体内外抗曲霉活性。在一项开放的多中心研究中，我们研究了泊沙康唑口服混悬液(800 mg/天，分次剂量)作为单一疗法在侵袭性曲霉病和其他对常规抗真菌治疗无效或不耐受的真菌病患者中的有效性和安全性。回顾性收集外对照病例资料，提供对照参考组。曲霉菌病病例被盲法数据审查委员会认为是可评估的，包括107名泊沙康唑接受者和86名对照受试者(修改的意向治疗人群)。在预先指定的人口学和疾病变量方面，这些人群是相似和平衡的。泊沙康唑受试者的总体成功率(即数据审查委员会评估的治疗结束时的全球反应)为42%，对照组为26%(优势比为4.06；95%可信区间为1.50-11.04；)。反应PP的差异。经修改的意向治疗组之间的差异在其他预先指定的亚组中保留，包括感染部位(肺部或播散性)、血液恶性肿瘤、造血干细胞移植、基线中性粒细胞减少症和入选原因(患者对先前的抗真菌治疗无效或不耐受)。药代动力学分析提示暴露-反应关系。尽管这项研究早于棘球菌素和伏立康唑的广泛使用，但这些发现表明泊沙康唑是对先前抗真菌治疗无效或不耐受的侵袭性曲霉病患者的抢救治疗的替代方案。
Background. Invasive aspergillosis is an important cause of morbidity and mortality in immunocompromised patients. Current treatments provide limited benefit. Posaconazole is an extended-spectrum triazole with in vitro and in vivo activity against Aspergillus species.Methods. We investigated the efficacy and safety of posaconazole oral suspension (800 mg/day in divided doses) as monotherapy in an open-label, multicenter study in patients with invasive aspergillosis and other mycoses who were refractory to or intolerant of conventional antifungal therapy. Data from external control cases were collected retrospectively to provide a comparative reference group.Results. Cases of aspergillosis deemed evaluable by a blinded data review committee included 107 posaconazole recipients and 86 control subjects (modified intent-to-treat population). The populations were similar and balanced with regard to prespecified demographic and disease variables. The overall success rate (i.e., the data review committee-assessed global response at the end of treatment) was 42% for posaconazole recipients and 26% for control subjects (odds ratio, 4.06; 95% confidence interval, 1.50-11.04;). The differences in response Pp. 006 between the modified intent-to-treat treatment groups were preserved across additional, prespecified subsets, including infection site (pulmonary or disseminated), hematological malignancy, hematopoietic stem cell transplantation, baseline neutropenia, and reason for enrollment(patient was refractory to or intolerant of previous antifungal therapy). An exposure-response relationship was suggested by pharmacokinetic analyses.Conclusions. Although the study predates extensive use of echinocandins and voriconazole, these findings demonstrate that posaconazole is an alternative to salvage therapy for patients with invasive aspergillosis who are refractory to or intolerant of previous antifungal therapy.