Efficacy of tocilizumab treatment in severely ill COVID-19 patients
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RESEARCH LETTER
Open Access
Efficacy of tocilizumab treatment in severely ill COVID-19 patients Jie Zhao, Wei Cui and Bao-ping Tian*
Keywords: Tocilizumab, COVID-19, Efficacy, Meta-analysis The current coronavirus disease 2019 (COVID-19) pandemic induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already caused a global increase in hospitalizations and deaths. Unfortunately, effective medicines to fight this disease, especially in the severely ill patients, are still lacking [1]. Tocilizumab, a humanized monoclonal antibody used in rheumatoid arthritis treatment, might also be effective in treating severe COVID-19 as it could selectively target the interleukin-6 (IL-6) receptor [2]. Considering the uncertain efficacy of tocilizumab treatment in severe COVID-19, we conducted a systematic review and meta-analysis to clarify this added effect of tocilizumab. We performed a systematic search of PubMed, Embase, Medline, Cochrane, and CNKI database through 25 July 2020, using the following search terms alone or in combination: (1) “COVID-19,” (2) “coronavirus,” (3) “SARS-CoV-2,” (4) “COVID,” (5) “antiinterleukin-6 receptor antibodies,” (6) “anti-IL-6 receptor antibodies,” (7) “anti-IL-6,” (8) “tocilizumab,” (9)“sarilumab,” and (10) “siltuximab.” Clinical trials regarding tocilizumab as a therapeutic intervention were selected. Two independent investigators selected eligible trials and extracted data from articles. Discrepancies in screening/data extraction were addressed by group discussion. Proportional variables were measured by odds ratio (OR) and corresponding 95% confidence intervals (CI). P values < 0.05 were * Correspondence: [email protected] Department of Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Rd., Hangzhou 310009, Zhejiang, China
considered statistically significant. Significant heterogeneity (P < 0.10 or I2 ≥ 50%) was evaluated by chisquare and I2 tests in a fixed-effect model. The comparison of the outcome between tocilizumab and control was conducted by using Review Manager 5.4 (Revman, The Cochrane Collaboration, Oxford, UK). Finally, 10 studies involving 1675 severe COVID-19 patients were included, among which only one trial was a randomized controlled trial, while the rest were all retrospective cohort studies. These studies included COVID-19 patients who were older/elderly (mean/median age ≥ 52 years) in America, Europe, and India, among whom 675 patients received tocilizumab, while 1000 patients underwent standard care. Severe COVID-19 patients received tocilizumab via intravenous or subcutaneous formulation, while doses and administration time points varied. Standard care included hydroxychloroquine, lopinavir/ritonavir, remdesivir, azithromycin, low weight heparin, and/or methylprednisolone, among others (Table 1). Our metaanalysis result revealed a significant difference in mortality between tocilizumab group (132/675, 19.5%) and control group (283/1000, 28.3%) in the fixed-effect model (OR, 0.47; 95%Cl,
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