Ma Zhuo, Sun Ximu, Zhao Zhixia, Lu Wenchao, Guo Qixiang, Wang Shihao, You Jiwen, Zhang Yuhui, Liu Lihong
Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, China.
Department of Pharmacy, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, No.17, Qi He Lou Street, Dongcheng District, Beijing, China.
Gynecol Oncol. 2021 Aug;162(2):496-505. doi: 10.1016/j.ygyno.2021.05.012. Epub 2021 May 19.
OBJECTIVE/BACKGROUND: We aimed to evaluate the risk of PARP inhibitors (PARPis) causing pneumonitis in randomized controlled trials (RCTs) and in the real-world practice.
First, a systematic review based on meta-analysis was conducted. RCTs with available data reporting pneumonitis events for PARPis were eligible for analysis. Second, we conducted a disproportionality analysis based on data from the FDA Adverse Event Reporting System (FAERS) database to characterize the main features of PARPi-related pneumonitis.
16 trials with 5771 patients were included in our meta-analysis. Compared with control arms, PARPis showed a significant increase in the risk of pneumonitis events (Peto OR 2.68 [95% CI 1.31-5.47], p = 0.007) with no heterogeneity (I = 0%, χp = 0.70). The incidence of pneumonitis across treatment arms was 0.79% (28/3551). In the FAERS database, we identified 84 cases of PARPi-pneumonitis with a fatality rate of 16% (13/79). The median time to event onset was 81 (interquartile range [IQR] 27-131) days and 87% of the adverse events occurred within 6 months.
PARPis increased the risk of pneumonitis that can result in serious outcomes and tend to occur early. Early recognition and management of PARPi-pneumonitis is of vital importance in clinical practice. The mechanisms and risk factors should be studied further to improve clinical understanding and innovative treatment strategies for these diseases.
目的/背景：我们旨在评估在随机对照试验（RCT）和实际临床实践中，聚（腺苷酸-核糖）聚合酶抑制剂（PARPis）导致肺炎的风险。
首先，进行了一项基于荟萃分析的系统评价。纳入报告了PARPis肺炎事件的可用数据的RCT进行分析。其次，我们基于美国食品药品监督管理局不良事件报告系统（FAERS）数据库的数据进行了不成比例分析，以描述PARPi相关肺炎的主要特征。
我们的荟萃分析纳入了16项试验中的5771例患者。与对照组相比，PARPis导致肺炎事件的风险显著增加（Peto比值比2.68 [95%可信区间1.31 - 5.47]，p = 0.007），且无异质性（I² = 0%，χ²p = 0.70）。各治疗组的肺炎发生率为0.79%（28/3551）。在FAERS数据库中，我们识别出84例PARPi相关肺炎病例，病死率为16%（13/79）。事件发生的中位时间为81天（四分位间距[IQR] 27 - 131天），87%的不良事件发生在6个月内。
PARPis增加了肺炎风险，可导致严重后果，且往往早期发生。在临床实践中，对PARPi相关肺炎的早期识别和管理至关重要。应进一步研究其机制和危险因素，以提高对这些疾病临床的认识并创新治疗策略。
