Voriconazole is frequently discontinued prematurely as primary antifungal prophylaxis (AFP) in allogeneic hematopoietic cell transplant (HCT) recipients due to adverse events. Limited data exists for isavuconazole as AFP. We analyzed adult HCT recipients who received voriconazole or isavuconazole AFP to estimate rate of premature AFP discontinuation, identify risk factors for premature AFP discontinuation, and compare incidence of invasive fungal infection (IFI) and survival at day + 180 post-HCT between patients who received voriconazole/isavuconazole-AFP. This was a propensity score matched cohort analysis of 210 HCT-recipients who received voriconazole-AFP (9/1/2014-12/31/2016; voriconazole-cohort), and 95 HCT-recipients who received isavuconazole-AFP (5/1/2017-10/31/2018; isavuconazole-cohort). AFP discontinuation for any reason prior to completion was defined as “premature”. Median (interquartile range, IQR) duration of AFP was longer in the isavuconazole-cohort (94 days, 87–100) vs. the voriconazole-cohort (76 days, 23–94; P-value < 0.0001). Premature AFP discontinuation was more frequent in the voriconazole-cohort (92/210, 43.8%) vs. the isavuconazole-cohort (14/95, 14.7%; P-value < 0.0001). The most common reason for premature discontinuation was biochemical hepatotoxicity (voriconazole-cohort: 48/210, 22.8% vs. isavuconazole-cohort: 5/95, 5.26%; P-value = 0.0002). Transaminase values between baseline and end-of-treatment (EOT) and up to 14 days post-EOT significantly increased in the voriconazole-cohort, but remained unchanged in the isavuconazole-cohort. The incidence of IFI at day + 180 was 2.9% (6/210) and 3.2% (3/95) in the voriconazole-cohort and isavuconazole-cohort, respectively (P-value = 0.881). All-cause mortality at day + 180 was 2.4% (5/210) and 6.3% (6/95) in the voriconazole-cohort and isavuconazole-cohort, respectively (P-value = 0.089). When compared to voriconazole, isavuconazole was a safer and as effective primary AFP during the first 3 months after HCT. Lay Summary When compared to voriconazole, isavuconazole is a safer and as effective primary antifungal prophylaxis during the first 3 months after allogeneic hematopoietic cell transplant, with lower rates of hepatotoxicity, and similar rates of fungal infections and all-cause mortality.

中文翻译：

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与伏立康唑相比，艾沙康唑作为同种异体造血细胞移植受者主要抗真菌预防的疗效和安全性

由于不良事件，伏立康唑作为同种异体造血细胞移植（HCT）受者的主要抗真菌预防（AFP）经常被过早停用。艾沙康唑作为 AFP 的数据有限。我们分析了接受伏立康唑或艾沙康唑 AFP 治疗的成年 HCT 接受者，以估计 AFP 提前停用的发生率，确定 AFP 过早停用的危险因素，并比较接受 HCT 治疗的患者之间侵袭性真菌感染 (IFI) 的发生率和 HCT 后第 180 天的生存率。伏立康唑/艾沙康唑-AFP。这是对 210 名接受伏立康唑-AFP 的 HCT 接受者（2014 年 9 月 1 日至 2016 年 12 月 31 日；伏立康唑队列）和 95 名接受艾沙康唑-AFP 的 HCT 接受者（5/1）进行倾向评分匹配队列分析。 /2017-10/31/2018；艾沙康唑队列）。在完成之前因任何原因终止 AFP 被定义为“过早”。艾沙康唑队列的 AFP 持续时间中位数（四分位距，IQR）较长（94 天，87-100），而伏立康唑队列（76 天，23-94；P 值 < 0.0001）更长。伏立康唑队列 (92/210, 43.8%) 与艾沙康唑队列 (14/95, 14.7%; P 值 < 0.0001) 相比，提前停用 AFP 更为频繁。过早停药的最常见原因是生化肝毒性（伏立康唑队列：48/210, 22.8% vs. 艾沙康唑队列：5/95, 5.26%；P 值 = 0.0002）。伏立康唑组中基线至治疗结束 (EOT) 之间以及 EOT 后 14 天的转氨酶值显着升高，但艾沙康唑组中转氨酶值保持不变。在伏立康唑队列和艾沙康唑队列中，第 + 180 天时的 IFI 发生率分别为 2.9% (6/210) 和 3.2% (3/95)（P 值 = 0.881）。在伏立康唑队列和艾沙康唑队列中，第 + 180 天的全因死亡率分别为 2.4% (5/210) 和 6.3% (6/95)（P 值 = 0.089）。与伏立康唑相比，艾沙康唑在 HCT 后的前 3 个月内是一种更安全、同样有效的主要 AFP。总结 与伏立康唑相比，艾沙康唑是同种异体造血细胞移植后前 3 个月内更安全、同样有效的主要抗真菌预防药物，其肝毒性发生率较低，真菌感染率和全因死亡率相似。