Wong Carlos K H, Lau Kristy T K, Au Ivan C H, Xiong Xi, Chung Matthew S H, Leung Belle Y C, Lau Eric H Y, Cowling Benjamin J
Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.
Department of Family Medicine and Primary Care, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.
Front Pharmacol. 2022 May 30;13:866441. doi: 10.3389/fphar.2022.866441. eCollection 2022.
This retrospective cohort study aims to explore head-to-head clinical outcomes and complications associated with tocilizumab or baricitinib initiation among hospitalized COVID-19 patients receiving dexamethasone. Among 10,445 COVID-19 patients hospitalized between January 21st 2020 and January 31st 2021 in Hong Kong, patients who had received tocilizumab ( = 165) or baricitinib ( = 76) while on dexamethasone were included. Primary study outcome was time to clinical improvement (at least one score reduction on WHO clinical progression scale). Secondary outcomes were disease progression, viral dynamics, in-hospital death, hyperinflammatory syndrome, and COVID-19/treatment-related complications. Hazard ratios (HR) of event outcomes were estimated using Cox regression models. The initiation of tocilizumab or baricitinib had no significant differences in time to clinical improvement (HR = 0.86, 95%CI 0.57-1.29, = 0.459), hospital discharge (HR = 0.85, 95%CI 0.57-1.27, = 0.418), recovery without the need for oxygen therapy (HR = 1.04, 95%CI 0.64-1.67, = 0.883), low viral load (HR = 1.49, 95%CI 0.85-2.60, = 0.162), and positive IgG antibody (HR = 0.97, 95%CI 0.61-1.54, = 0.909). Time to viral clearance (HR = 1.94, 95%CI 1.01-3.73, = 0.048) was shorter in the tocilizumab group with marginal significance, compared to that of baricitinib. Meanwhile, the two treatment modalities were not significantly different in their associated risks of in-hospital death (HR = 0.63, 95%CI 0.29-1.35, = 0.233), severe liver injury (HR = 1.15, 95%CI 0.43-3.08, = 0.778), acute renal failure (HR = 2.33, 95%CI 0.61-8.82, = 0.213), hyperinflammatory syndrome (HR = 2.32, 95%CI 0.87-6.25, = 0.091), thrombotic and bleeding events (HR = 1.39, 95%CI 0.32-6.00, = 0.658), and secondary infection (HR = 2.97, 95%CI 0.62-14.31, = 0.173). Among hospitalized patients with moderate-to-severe COVID-19 on background dexamethasone, the initiation of tocilizumab or baricitinib had generally comparable effects on time to clinical improvement, hospital discharge, recovery, low viral load, and positive IgG antibody; risks of in-hospital death, hepatic and renal complications, hyperinflammatory syndrome, thrombotic and bleeding events, and secondary infection. On the other hand, tocilizumab users might achieve viral clearance slightly faster than baricitinib users. Further studies and clinical trials are needed to confirm our findings regarding the evaluation of tocilizumab and baricitinib in COVID-19 patients with different disease severities, at varying stages or timing of drug initiation, and considering the concomitant use of other therapeutics.
这项回顾性队列研究旨在探讨在接受地塞米松治疗的住院COVID-19患者中,使用托珠单抗或巴瑞替尼起始治疗后的直接临床结局和并发症。在2020年1月21日至2021年1月31日期间在香港住院的10445例COVID-19患者中,纳入了在接受地塞米松治疗期间接受过托珠单抗(n = 165)或巴瑞替尼(n = 76)治疗的患者。主要研究结局是临床改善时间(世界卫生组织临床进展量表上至少降低一个评分)。次要结局包括疾病进展、病毒动态变化、院内死亡、高炎症综合征以及与COVID-19/治疗相关的并发症。使用Cox回归模型估计事件结局的风险比(HR)。托珠单抗或巴瑞替尼起始治疗在临床改善时间(HR = 0.86,95%CI 0.57 - 1.29,P = 0.459)、出院(HR = 0.85,95%CI 0.57 - 1.27,P = 0.418)、无需吸氧治疗即可康复(HR = 1.04,95%CI 0.64 - 1.67,P = 0.883)、低病毒载量(HR = 1.49,95%CI 0.85 - 2.60,P = 0.162)和IgG抗体阳性(HR = 0.97,95%CI 0.61 - 1.54,P = 0.909)方面无显著差异。与巴瑞替尼组相比,托珠单抗组的病毒清除时间(HR = 1.94,95%CI 1.01 - 3.73,P = 0.048)稍短,具有边缘显著性。同时,两种治疗方式在院内死亡(HR = 0.63,95%CI 0.29 - 1.35,P = 0.233)、严重肝损伤(HR = 1.15,95%CI 0.43 - 3.08,P = 0.778)、急性肾衰竭(HR = 2.33,95%CI 0.61 - 8.82,P = 0.213)、高炎症综合征(HR = 2.32,95%CI 0.87 - 6.25,P = 0.091)、血栓形成和出血事件(HR = 1.39,95%CI 0.32 - 6.00,P = 0.658)以及继发感染(HR = 2.97,95%CI 0.62 - 14.31,P = 0.173)的相关风险方面无显著差异。在接受背景地塞米松治疗的中重度COVID-19住院患者中,托珠单抗或巴瑞替尼起始治疗在临床改善时间、出院、康复、低病毒载量和IgG抗体阳性方面的总体效果相当;在院内死亡、肝和肾并发症、高炎症综合征以及血栓形成和出血事件、继发感染风险方面也是如此。另一方面,使用托珠单抗的患者可能比使用巴瑞替尼的患者实现病毒清除的速度略快。需要进一步的研究和临床试验来证实我们关于在不同疾病严重程度、不同药物起始阶段或时间以及考虑其他治疗药物联合使用的情况下,评估托珠单抗和巴瑞替尼在COVID-19患者中的研究结果。