Remdesivir and Acute Renal Failure: A Potential Safety Signal From Disproportionality Analysis of the WHO Safety Database
Remdesivir and Acute Renal Failure: A Potential Safety Signal From Disproportionality Analysis of the WHO Safety Database
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DOI：
10.1002/cpt.2145
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发表时间：
2021-01-16
影响因子：
6.7
通讯作者：
Drici, Milou-Daniel
中科院分区：
文献类型：
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作者：
Gerard, Alexandre O.;Laurain, Audrey;Drici, Milou-Daniel
Remdesivir被美国食品和药物管理局（FDA）批准紧急使用，并被欧洲药品管理局（EMA）有条件地批准用于2019冠状病毒病（COVID-19）患者。由于该领域的数据相当缺乏，其收益风险比仍在探索中。在临床试验中，与瑞德西韦相关的肌酐清除率降低的报道并不频繁，相关性不明确。尽管存在这些不确定性，我们在上市后的药物警戒数据中寻找急性肾功能衰竭（ARF）的潜在信号。使用两种歧化方法对世界卫生组织（WHO）的国际药物警戒上市后数据库（VigiBase）进行了分析。报告优势比（ROR）比较了在COVID-19类似情况下使用瑞德西韦报告的ARF病例数与使用其他药物（羟氯喹、托珠单抗和洛匹那韦/利托那韦）报告的ARF病例数。术语“急性肾功能衰竭”和“remdesivir”的组合产生了统计学上显著的歧化信号，观察到138例，而不是预期的9例。瑞德西韦ARF的ROR是对照药物的20倍（20.3，置信区间0.95 [15.7-26.3],P < 0.0001]）。根据VigiBase中报告的ARF病例，尽管存在COVID-19环境固有的警告，但我们发现了与瑞德西韦相关的具有统计学意义的肾毒性药物警戒信号，值得对所有可用数据进行彻底的定性评估。同时，根据其产品特性总结建议，在COVID-19患者使用瑞德西韦治疗前和治疗期间，应优先评估患者的肾功能。
Remdesivir is approved for emergency use by the US Food and Drug Administration (FDA) and authorized conditionally by the European Medicines Agency (EMA) for patients with coronavirus disease 2019 (COVID-19). Its benefit-risk ratio is still being explored because data in the field are rather scant. A decrease of the creatinine clearance associated with remdesivir has been inconstantly reported in clinical trials with unclear relevance. Despite these uncertainties, we searched for a potential signal of acute renal failure (ARF) in pharmacovigilance postmarketing data. An analysis of the international pharmacovigilance postmarketing databases (VigiBase) of the World Health Organization (WHO) was performed, using two disproportionality methods. Reporting odds ratio (ROR) compared the number of ARF cases reported with remdesivir, with those reported with other drugs prescribed in comparable situations of COVID-19 (hydroxychloroquine, tocilizumab, and lopinavir/ritonavir). The combination of the terms "acute renal failure" and "remdesivir" yielded a statistically significant disproportionality signal with 138 observed cases instead of the 9 expected. ROR of ARF with remdesivir was 20-fold (20.3; confidence interval 0.95 [15.7-26.3], P < 0.0001]) that of comparative drugs. Based on ARF cases reported in VigiBase, and despite the caveats inherent to COVID-19 circumstances, we detected a statistically significant pharmacovigilance signal of nephrotoxicity associated with remdesivir, deserving a thorough qualitative assessment of all available data. Meanwhile, as recommended in its Summary of Product Characteristics, assessment of patients with COVID-19 renal function should prevail before and during treatment with remdesivir in COVID-19.