Department of Clinical Pharmacology, Seth GS Medical College & KEM Hospital, Parel-400 012, Mumbai, Maharashtra, India.
Curr Drug Saf. 2022;17(2):158-167. doi: 10.2174/1574886316666210728110330.
Remdesivir is an adenosine analogue drug that targets RNA-dependent RNA polymerase enzyme and inhibits viral replication. As of 22nd October, 2020, US FDA fully approved the drug Remdesivir for the treatment of COVID-19 patients who requires hospitalisation. Many clinical studies reported the derangement in hepatic and renal function tests, which is alarming considering the health conditions of the COVID-19 patients. In view of these results, the present study was envisaged to review the safety of Remdesivir in COVID-19 patients. The PubMed, Embase, and Cochrane databases were searched using the terms 'Remdesivir,' 'veklury,' 'SARS' and 'COVID' till 1st December, 2020. The studies included in this meta-analysis were either randomised or nonrandomised studies that evaluated Remdesivir for the treatment of COVID-19 against Placebo [standard of care]. The Adverse events [AEs], Serious adverse events [SAEs] and Treatment Discontinuation due to Adverse Events (TDAE) were used as primary outcome measures. The quality of studies was evaluated by using the Cochrane Collaboration's tool for the assessment of RoB. Data analysis was performed by two authors (MK & DB) using statistical software Review manager [Revman] version 5.3. The pooled Risk Ratios (RR) and 95% Confidence Intervals (CI) were calculated by using a random-effects model for both primary and secondary outcomes. A total of four RCTs were included for the meta-analysis. Out of the four included clinical trials accepted for its methodological quality, three were of excellent quality and one study was of moderate quality. The pooled estimates of the three studies showed that Remdesivir had a 24% lower risk of SAEs compared to the placebo arm. However, the pooled estimates of two studies showed that 10 days of Remdesivir had 56% higher risk of SAEs compared to 5 days of Remdesivir regimen. Similarly, the 10 days of Remdesivir had two times higher risk of TDAEs compared to 5 days Remdesivir regimen. In conclusion, our meta-analysis demonstrated that Remdesivir is a safe therapeutic option. Our metanalysis revealed 5 days' regimen have better safety profile than 10 days' regimen of drug Remdesivir with respect to SAEs and TDAEs. For hospitalized patients, a 5-day course could be preferable with fewer safety concerns and lower drug costs. PROSPERO Registration ID: CRD 42020224272.
瑞德西韦是一种靶向 RNA 依赖性 RNA 聚合酶的腺嘌呤类似物药物，可抑制病毒复制。截至 2020 年 10 月 22 日，美国食品药品监督管理局（FDA）全面批准瑞德西韦用于治疗需要住院的 COVID-19 患者。许多临床研究报告了肝功能和肾功能测试的紊乱，考虑到 COVID-19 患者的健康状况，这令人担忧。有鉴于此，本研究旨在评估瑞德西韦治疗 COVID-19 患者的安全性。使用术语“Remdesivir”、“Veklury”、“SARS”和“COVID”，在 PubMed、Embase 和 Cochrane 数据库中进行检索，检索时间截至 2020 年 12 月 1 日。本荟萃分析纳入的研究为评估瑞德西韦治疗 COVID-19 与安慰剂（标准治疗）的随机或非随机研究。主要结局指标为不良事件（AE）、严重不良事件（SAE）和因不良事件（TDAE）而停药。使用 Cochrane 协作组的评估 RoB 工具评估研究质量。两名作者（MK 和 DB）使用统计软件 Review Manager [Revman] 版本 5.3 分析数据。使用随机效应模型计算主要和次要结局的汇总风险比（RR）和 95%置信区间（CI）。共纳入四项 RCT 进行荟萃分析。在纳入的四项临床试验中，有四项因方法学质量而被接受，其中三项为高质量研究，一项为中质量研究。三项研究的汇总估计结果表明，与安慰剂组相比，瑞德西韦治疗组发生 SAE 的风险降低了 24%。然而，两项研究的汇总估计结果表明，与 5 天的瑞德西韦治疗方案相比，10 天的瑞德西韦治疗方案发生 SAE 的风险增加了 56%。同样，10 天的瑞德西韦治疗方案发生 TDAE 的风险是 5 天瑞德西韦治疗方案的两倍。总之，我们的荟萃分析表明，瑞德西韦是一种安全的治疗选择。我们的荟萃分析表明，与 10 天的瑞德西韦治疗方案相比，5 天的治疗方案在 SAE 和 TDAE 方面具有更好的安全性。对于住院患者，5 天的疗程可能更可取，安全性问题更少，药物成本更低。PROSPERO 注册号：CRD 42020224272。
