背景:疗效,有效性,批准的尼马特雷韦/利托那韦方案治疗实验室确诊的轻度/中度COVID-19的安全性尚不清楚.
方法:我们系统地确定了已批准的尼马特雷韦/利托那韦方案治疗COVID-19的疗效/有效性和/或安全性的随机对照试验(RCT)和真实世界研究(RWS;观察性研究)。我们使用逆方差汇集了适当的数据(RWS的调整估计),随机效应模型。我们使用I2统计量计算了统计异质性。结果以95%CI相关的相对风险(RR)表示。我们进一步评估偏倚风险/研究质量,并对来自随机对照试验的证据进行试验序贯分析。
结果:我们纳入了4个RCT(4,070人)和16个RWS(1,925,047人)的成年人(年龄≥18岁)。1个和3个随机对照试验的偏倚风险较低且不清楚,分别。RWS质量良好。与安慰剂/无治疗相比,尼马特雷韦/利托那韦显着降低了COVID-19的住院率(RR=0.17;95%CI,0.10-0.31;I2=77.2%;2个随机对照试验,3,542人),但恶化严重程度的降低没有显着差异(RR=0.82;95%CI,0.66-1.01;I2=47.5%;3项RCT,1,824人),病毒清除率(RR=1.19;95%CI,0.93-1.51;I2=82%;2个随机对照试验,528人),不良事件(RR=1.41;95%CI,0.92-2.14;I2=70.6%;4项随机对照试验,4,070人),严重不良事件(RR=0.82;95%CI,0.41-1.62;I2=0%;3项随机对照试验,3,806人),和全因死亡率(RR=0.27;95%CI,0.04-1.70;I2=49.9%;3项随机对照试验,3,806人),尽管试验序贯分析表明,目前这些结局的总样本量不足以得出结论.真实世界研究还显示,COVID-19住院率显着降低(RR=0.48;95%CI,0.37-0.60;I2=95.0%;11RWS,1,421,398人)和全因死亡率(RR=0.24;95%CI,0.14-0.34;I2=65%;7RWS,286,131人)与不治疗相比,尼马特雷韦/利托那韦。
结论:Nirmatrelvir/利托那韦对于预防轻度/中度COVID-19患者的住院和可能降低全因死亡率似乎很有希望,但证据不足。需要更多的研究。
BACKGROUND: The efficacy, effectiveness, and safety of the approved nirmatrelvir/ritonavir regimen for treatment of laboratory-confirmed mild/moderately severe COVID-19 remains unclear.
METHODS: We systematically identified randomized controlled trials (RCTs) and real-world studies (RWS; observational studies) of the efficacy/effectiveness and/or safety of the approved nirmatrelvir/ritonavir regimen for COVID-19. We pooled appropriate data (adjusted estimates for RWS) using an inverse variance, random-effects model. We calculated statistical heterogeneity using the I 2 statistic. Results are presented as relative risk (RR) with associated 95% CI. We further assessed risk of bias/
study quality and conducted
trial sequential analysis of the evidence from RCTs.
RESULTS: We included 4 RCTs (4,070 persons) and 16 RWS (1,925,047 persons) of adults (aged ≥18 years). One and 3 RCTs were of low and unclear risk of bias, respectively. The RWS were of good quality. Nirmatrelvir/ritonavir significantly decreased COVID-19 hospitalization compared with placebo/no treatment (RR = 0.17; 95% CI, 0.10-0.31; I 2 = 77.2%; 2 RCTs, 3,542 persons), but there was no significant difference for decrease of worsening severity (RR = 0.82; 95% CI, 0.66-1.01; I 2 = 47.5%; 3 RCTs, 1,824 persons), viral clearance (RR = 1.19; 95% CI, 0.93-1.51; I 2 = 82%; 2 RCTs, 528 persons), adverse events (RR = 1.41; 95% CI, 0.92-2.14; I 2 = 70.6%; 4 RCTs, 4,070 persons), serious adverse events (RR = 0.82; 95% CI, 0.41-1.62; I 2 = 0%; 3 RCTs, 3,806 persons), and all-cause mortality (RR = 0.27; 95% CI, 0.04-1.70; I 2 = 49.9%; 3 RCTs, 3,806 persons), although
trial sequential analysis suggested that the current total sample sizes for these outcomes were not large enough for conclusions to be drawn. Real-world studies also showed significantly decreased COVID-19 hospitalization (RR = 0.48; 95% CI, 0.37-0.60; I 2 = 95.0%; 11 RWS, 1,421,398 persons) and all-cause mortality (RR = 0.24; 95% CI, 0.14-0.34; I 2 = 65%; 7 RWS, 286,131 persons) for nirmatrelvir/ritonavir compared with no treatment.
CONCLUSIONS: Nirmatrelvir/ritonavir appears to be promising for preventing hospitalization and potentially decreasing all-cause mortality for persons with mild/moderately severe COVID-19, but the evidence is weak. More studies are needed.