Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
BMJ Open. 2021 Jun 24;11(6):e048416. doi: 10.1136/bmjopen-2020-048416.
Evaluation of remdesivir, an RNA polymerase inhibitor, for effectiveness in adults with COVID-19.
Electronic search for eligible articles of PubMed, Cochrane Central and clinicaltrials.gov was performed on 20 September 2020.
Only randomised controlled trials (RCTs) evaluating efficacy of remdesivir in COVID-19 were included for meta-analysis.
Remdesivir was compared with standard of care.
Primary outcome was mortality and secondary outcomes were time to clinical improvement and safety outcomes like serious adverse events, respiratory failure.
Data synthesis was done with Cochrane review manager 5 (RevMan) V.5.3. Cochrane risk of bias V.2.0 tool was used for methodological quality assessment. The GRADE pro GDT was applied for overall quality of evidence.
52 RCTs were screened and 4 studies were included in analysis, with total of 7324 patients. No mortality benefit was observed with remdesivir versus control group (OR=0.92 (95% CI 0.79 to 1.07), p=0.30, moderate quality evidence). Significantly higher rates of clinical improvement (OR=1.52 (95% CI 1.24 to 1.87), p<0.0001, low quality) and faster time to clinical improvement (HR=1.28 (95% CI 1.12 to 1.46), p=0.0002, very low quality) was observed with remdesivir versus control group. Significant decrease was found in the risk of serious adverse events (RR=0.75 (95% CI 0.62 to 0.90), p=0.0003, low quality); however, no difference was found in the risk of respiratory failure (RR=0.85 (95% CI 0.41 to 1.77), p=0.67, very low quality evidence) with remdesivir.
As per the evidence from current review, remdesivir has shown no mortality benefit (moderate quality evidence) in the treatment of COVID-19. From a cost-benefit perspective, it is our personal opinion that it should not be recommended for use, especially in low and lower middle income countries.
PROSPERO registration number: CRD42020189517.
评估瑞德西韦(一种 RNA 聚合酶抑制剂)对 COVID-19 成人患者的疗效。
2020 年 9 月 20 日,对 PubMed、Cochrane 中央和 clinicaltrials.gov 中符合条件的文章进行电子检索。
仅纳入评估瑞德西韦治疗 COVID-19 的随机对照试验(RCT)进行荟萃分析。
将瑞德西韦与标准护理进行比较。
主要结局为死亡率,次要结局为临床改善时间和安全性结局,如严重不良事件、呼吸衰竭。
使用 Cochrane 评论经理 5(RevMan)V.5.3 进行数据综合。使用 Cochrane 偏倚风险 V.2.0 工具评估方法学质量。应用 GRADE pro GDT 评估总体证据质量。
筛选了 52 项 RCT,有 4 项研究纳入分析,共纳入 7324 例患者。与对照组相比,瑞德西韦组未观察到死亡率获益(OR=0.92(95% CI 0.79 至 1.07),p=0.30,中等质量证据)。与对照组相比,瑞德西韦组临床改善的比例显著更高(OR=1.52(95% CI 1.24 至 1.87),p<0.0001,低质量),临床改善时间更快(HR=1.28(95% CI 1.12 至 1.46),p=0.0002,极低质量)。与对照组相比,瑞德西韦组严重不良事件的风险显著降低(RR=0.75(95% CI 0.62 至 0.90),p=0.0003,低质量);然而,瑞德西韦组呼吸衰竭的风险无差异(RR=0.85(95% CI 0.41 至 1.77),p=0.67,极低质量证据)。
根据当前综述的证据,瑞德西韦在治疗 COVID-19 方面未显示出死亡率获益(中等质量证据)。从成本效益的角度来看,我们个人认为不应该推荐使用瑞德西韦,特别是在低收入和中低收入国家。
PROSPERO 注册号:CRD42020189517。