Systematic review and meta-analysis of tocilizumab in persons with coronavirus disease-2019 (COVID-19)

Abstract

We performed a meta-analysis to determine safety and efficacy of tocilizumab in persons with coronavirus disease-2019 (COVID-19). We searched PubMed, Web of Science and Medline using Boolean operators for studies with the terms coronavirus OR COVID-19 OR 2019-nCoV OR SARS-CoV-2 AND tocilizumab. Review Manager 5.4 was used to analyze data and the modified Newcastle–Ottawa and Jadad scales for quality assessment. We identified 32 studies in 11,487 subjects including three randomized trials and 29 cohort studies with a comparator cohort, including historical controls (N\u2009=\u20095), a matched cohort (N\u2009=\u200912), or concurrent controls (N\u2009=\u200912). Overall, tocilizumab decreased risk of death (Relative Risk [RR]\u2009=\u20090.74; 95% confidence interval [CI], 0.59, 0.93; P\u2009=\u20090.008; I2\u2009=\u200980%) but not of surrogate endpoints including ICU admission (RR\u2009=\u20091.40 [0.64,3.06]; P\u2009=\u20090.4; I2\u2009=\u200988%), invasive mechanical ventilation (RR\u2009=\u20090.83 [0.57,1.22]; P\u2009=\u20090.34; I2\u2009=\u200965%) or secondary infections (RR\u2009=\u20091.30 [0.97,1.74]; P\u2009=\u20090.08; I2\u2009=\u200965%) and increased interval of hospitalization of subjects discharged alive(mean difference [MD]\u2009=\u20092 days [<1, 4 days]; P\u2009=\u20090.006; I2\u2009=\u20090). RRs of death in studies with historical controls (RR\u2009=\u20090.28 [0.16,0.49; P\u2009<\u20090.001]; I2\u2009=\u200962%) or a matched cohort (RR\u2009=\u20090.68 [0.53, 0.87]; P\u2009=\u20090.002; I2\u2009=\u200942%) were decreased. In contrast, RRs of death in studies with a concurrent control (RR\u2009=\u20091.10 [0.77, 1.56]; P\u2009=\u20090.60; I2\u2009=\u200985%) or randomized (RR\u2009=\u20091.18 [0.57,2.44]; P\u2009=\u20090.66; I2\u2009=\u20090) were not decreased. A reduced risk of death was not confirmed in our analyses which questions safety and efficacy of tocilizumab in persons with COVID-19.