Department of Rheumatology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran.
Immunoregulation Research Center, Shahed University, Tehran, Iran.
Int Immunopharmacol. 2023 Sep;122:110565. doi: 10.1016/j.intimp.2023.110565. Epub 2023 Jun 30.
The efficacy and safety of a strong Janus kinase inhibitor, tofacitinib, in individuals suffering from severe coronavirus disease 2019 (Covid-19) pneumonia are not definite well.
In this non-randomized and non-blinded trial, a total of 52 Iranian patients with severe COVID-19 associated with decreased oxygen saturation, elevated C-reactive protein, and/or persistent fever were included. A total of 52 patients were included in this study. Tofacitinib was administered to 29 patients (55.8%) in addition to the standard care treatments, whereas 23 patients (44.2%) were treated with the standard of care alone (mostly antiviral agents and corticosteroids). Tofacitinib was administered at a dose of 5 mg twice daily for up to 10 days. The primary outcomes were mortality rate, oxygen saturation level, CT findings, rate of breath, heart rate, and level of consciousness. Inflammatory cytokines and blood biomarkers were considered as the secondary outcomes.
Death from any cause through day 14 occurred in 51.7% of the tofacitinib group and 65.2% of the control group. There was no significant difference in lung radiographic findings between the intervention and control groups at the first day of the study and after the study period. However, a significant decrease was observed in the extent of lung tissue involvement in the intervention group after administration of tofacitinib. Regarding cell and blood biomarkers, a significant decrease in the CPK levels in the intervention group and Hct and ACE levels in the control group was observed after fourteen days of the study. Moreover, a significant increase in SGOT and ferritin values was detected in the control group 14 days after the beginning tofacitinib administration. Comparing control and intervention groups, there was a significant difference in hemoglobin, SGOT, LDH, ferritin, and ACE values between groups before the intervention, while after fourteen days of the study, no significant difference was found. In case of DHEAS and TSH levels, a significant decrease was seen in the intervention group compared to the control after the study period. No other significant improvement was detected in other outcomes of the tofacitinib group compared to the control.
The administration of tofacitinib combined with corticosteroids, is not effective enough to treat severe COVID-19 patients and the use of this medication should be considered before the disease deterioration.
一种强效的 Janus 激酶抑制剂托法替布治疗严重 2019 冠状病毒病（COVID-19）肺炎患者的疗效和安全性尚未明确。
在这项非随机、非盲法试验中，共纳入了 52 例伊朗严重 COVID-19 患者，这些患者伴有氧饱和度降低、C 反应蛋白升高和/或持续发热。共纳入 52 例患者。其中 29 例（55.8%）在标准治疗的基础上加用托法替布，23 例（44.2%）仅接受标准治疗（主要为抗病毒药物和皮质类固醇）。托法替布的剂量为 5mg，每日 2 次，连用 10 天。主要结局是死亡率、氧饱和度、CT 表现、呼吸频率、心率和意识水平。炎症细胞因子和血液生物标志物被认为是次要结局。
托法替布组和对照组在第 14 天的死亡率分别为 51.7%和 65.2%。研究第一天和研究期间，干预组和对照组的肺部放射学表现无显著差异。然而，在托法替布治疗后，干预组肺部组织受累的程度显著下降。在细胞和血液生物标志物方面，干预组在研究第 14 天 CPK 水平显著下降，对照组 Hct 和 ACE 水平显著下降。此外，在开始托法替布治疗后 14 天，对照组 SGOT 和铁蛋白值显著升高。与对照组相比，干预组血红蛋白、SGOT、LDH、铁蛋白和 ACE 值在干预前有显著差异，而在研究 14 天后无显著差异。在 DHEAS 和 TSH 水平方面，与对照组相比，干预组在研究后显著下降。与对照组相比，托法替布组其他结局无显著改善。
托法替布联合皮质类固醇治疗严重 COVID-19 患者效果不够显著，应在病情恶化前考虑使用该药物。
