Cherian Jerin Jose, Eerike Madhavi, Bagepally Bhavani Shankara, Das Saibal, Panda Samiran
Indian Council of Medical Research, New Delhi, India.
Department of Pharmacology, All India Institute of Medical Sciences, Bibinagar, India.
Front Pharmacol. 2022 Oct 14;13:1004308. doi: 10.3389/fphar.2022.1004308. eCollection 2022.
This review was performed to compare the efficacy and safety among hospitalized patients with COVID-19 who received baricitinib and those who received tocilizumab independently with placebo or the standard of care (SOC). Relevant databases were searched for randomized controlled trials which evaluated the effect of baricitinib or tocilizumab as compared to placebo or the SOC in hospitalized patients with COVID-19. The primary endpoint was the comparison of the 28-day mortality. Risk ratios (RR) and mean differences were compared and pooled for dichotomous and continuous variables, respectively. A two-staged exploratory network meta-analysis using a multivariate meta-analysis was also performed. All analyses were performed in Stata version 16.0. The GRADE approach was used to assess the quality of the generated evidence (PROSPERO ID: CRD42022323363). Treatment with baricitinib [RR, 0.69 (95% CI, 0.50-0.94), = 0.02, i = 64.86%] but not with tocilizumab [RR, 0.87 (95% CI, 0.71-1.07), = 0.19, i = 24.41%] led to a significant improvement in the 28-day mortality as compared to that with the SOC. Treatment with baricitinib or tocilizumab, both independently led to a significant reduction in the duration of hospitalization [baricitinib: mean difference, -1.13 days (95% CI, -1.51 to -0.76), < 0.001, i = 0.00%; tocilizumab: mean difference, -2.80 days (95% CI, -4.17 to -1.43), < 0.001, i = 55.47%] and a significant improvement in the proportion of patients recovering clinically by day 28 [baricitinib: RR, 1.24 (95% CI, 1.03-1.48), = 0.02, i = 27.20%; tocilizumab: RR, 1.41 (95% CI, 1.12-1.78), < 0.001, i = 34.59%] as compared to those with the SOC. From the safety point of view, both these drugs showed similar results. There were fewer patients who experienced any serious adverse event following treatment with barictinib and tocilizumab as compared to those following treatment with the SOC [baricitinib: RR, 0.76 (95% CI, 0.62-0.92), = 0.01, i = 12.63%; tocilizumab: RR, 0.85 (95% CI, 0.72-1.01), = 0.07, i = 0.00%]. As baricitinib and tocilizumab are recommended interchangeably by various guidelines for the management of COVID-19, considering the better 28-day mortality data and other comparable efficacy and safety outcomes, baricitinib may be favored over tocilizumab considering its ease of administration, shorter half-life, and lower cost of treatment.
本综述旨在比较接受巴瑞替尼和接受托珠单抗治疗的COVID-19住院患者与接受安慰剂或标准治疗(SOC)的患者之间的疗效和安全性。检索相关数据库,查找评估巴瑞替尼或托珠单抗与安慰剂或SOC相比在COVID-19住院患者中的疗效的随机对照试验。主要终点是比较28天死亡率。分别对二分类变量和连续变量比较并汇总风险比(RR)和均值差。还使用多变量荟萃分析进行了两阶段探索性网状荟萃分析。所有分析均在Stata 16.0版本中进行。采用GRADE方法评估所产生证据的质量(PROSPERO编号:CRD42022323363)。与SOC相比,巴瑞替尼治疗[RR,0.69(95%CI,0.50 - 0.94),P = 0.02,I² = 64.86%]可显著改善28天死亡率,而托珠单抗治疗[RR,0.87(95%CI,0.71 - 1.07),P = 0.19,I² = 24.41%]则无显著改善。与SOC相比,巴瑞替尼或托珠单抗治疗均能显著缩短住院时间[巴瑞替尼:均值差,-1.13天(95%CI,-1.51至-0.76),P < 0.001,I² = 0.00%;托珠单抗:均值差,-2.80天(95%CI,-4.17至-1.43),P < 0.001,I² = 55.47%],并显著提高28天时临床康复患者的比例[巴瑞替尼:RR,1.24(95%CI,1.03 - 1.48),P = 0.02,I² = 27.20%;托珠单抗:RR,1.41(95%CI,1.12 - 1.78),P < 0.001,I² = 34.59%]。从安全性角度来看,这两种药物显示出相似的结果。与SOC治疗相比,接受巴瑞替尼和托珠单抗治疗后发生任何严重不良事件的患者较少[巴瑞替尼:RR,0.76(95%CI,0.62 - 0.92),P = 0.01,I² = 12.63%;托珠单抗:RR,0.85(95%CI,0.72 - 1.01),P = 0.07,I² = 0.00%]。由于各种COVID-19管理指南可互换推荐使用巴瑞替尼和托珠单抗,考虑到更好的28天死亡率数据以及其他相当的疗效和安全性结果,鉴于巴瑞替尼给药方便、半衰期较短且治疗成本较低,巴瑞替尼可能比托珠单抗更受青睐。