Chen Yan, Zhao Jiaojiao, Wang Yifei, Ge Long, Kwong Joey Sum-Wing, Lan Junjie, Zhang Rui, Zhao Huaye, Hu Linfang, Wang Jiaxue, Sun Shuimei, Tan Songsong, Lin Xiaoqing, He Rui, Zheng Wenyi, Li Xiaosi, Zhang Jiaxing
School of Pharmaceutical Sciences, Guizhou University, Guiyang, China.
Department of Pharmacy, Guizhou Provincial People's Hospital, Guiyang, China.
Front Pharmacol. 2025 Jan 15;15:1530999. doi: 10.3389/fphar.2024.1530999. eCollection 2024.
Several antifungals are available for the treatment of patients with invasive aspergillosis (IA). This study aims to evaluate the relative efficacy and safety of the first-line monotherapies in primary therapy of IA through network meta-analysis (NMA).
We systematically searched PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, VIP database, Wanfang database, and China Biology Medicine for randomized controlled trials (RCTs) up to July 2023 that evaluated the efficacy and safety of monotherapies. We performed NMA with a frequentist random effects model and assessed the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Primary outcomes were the all-cause mortality at week 12, and secondary outcomes included overall response rate, and incidence of adverse events (AEs) and severe adverse events (SAEs).
A total of three RCTs involving 1,368 participants (four antifungals) were included. The NMA showed that compared to amphotericin B deoxycholate (D-AmB), the triazoles (posaconazole (POS), isavuconazole (ISA) and voriconazole (VCZ)) can improve the overall response rate in primary therapy of IA, but only VCZ and ISA can reduce the all-cause mortality at week 12 for patients with proven and probable IA (VCZ vs D-AmB: RR = 0.66, 95%CI = 0.47-0.93, moderate certainty; ISA vs D-AmB: RR = 0.52, 95%CI = 0 .31-0.86, low certainty). ISA (SUCRA = 93.50%; mean rank, 1.20) seemed to be the most effective therapy in the above population. As to proven, probable, and possible IA patients, the triazoles were superior to D-AmB in terms of reducing all-cause mortality. Furthermore, the risk of AEs and SAEs was comparable for the three triazoles, but the risk of SAEs was significantly higher for D-AmB than others.
The efficacy and safety of triazoles are more favorable than D-AmB in the primary therapy of IA, with ISA being the optimal choice.
PROSPERO CRD42023407632.
有几种抗真菌药物可用于治疗侵袭性曲霉病（IA）患者。本研究旨在通过网状Meta分析（NMA）评估一线单药疗法在IA初始治疗中的相对疗效和安全性。
我们系统检索了截至2023年7月的PubMed、Embase、Web of Science、Cochrane图书馆、中国知网、维普数据库、万方数据库和中国生物医学数据库，以查找评估单药疗法疗效和安全性的随机对照试验（RCT）。我们使用频率随机效应模型进行NMA，并采用GRADE（推荐分级评估、制定和评价）方法评估证据的确定性。主要结局是第12周的全因死亡率，次要结局包括总体缓解率、不良事件（AE）和严重不良事件（SAE）的发生率。
共纳入3项涉及1368名参与者（4种抗真菌药物）的RCT。NMA显示，与两性霉素B去氧胆酸盐（D-AmB）相比，三唑类药物（泊沙康唑（POS）、艾沙康唑（ISA）和伏立康唑（VCZ））可提高IA初始治疗的总体缓解率，但只有VCZ和ISA可降低确诊和疑似IA患者第12周的全因死亡率（VCZ与D-AmB相比：RR = 0.66，95%CI = 0.47-0.93，中等确定性；ISA与D-AmB相比：RR = 0.52，95%CI = 0.31-0.86，低确定性）。ISA（累积排序曲线下面积（SUCRA）= 93.50%；平均排名，1.20）似乎是上述人群中最有效的治疗方法。对于确诊、疑似和可能的IA患者，三唑类药物在降低全因死亡率方面优于D-AmB。此外，三种三唑类药物的AE和SAE风险相当，但D-AmB的SAE风险明显高于其他药物。
在IA的初始治疗中，三唑类药物的疗效和安全性优于D-AmB，其中ISA是最佳选择。
PROSPERO CRD42023407632。
