Clin Microbiol Infect. 2021 Apr 26:S1198-743X(21)00204-4. doi: 10.1016/j.cmi.2021.04.019. Online ahead of print.
BACKGROUND: Cytokine release syndrome with elevated interleukin-6 (IL-6) levels is associated with multiorgan damage and death in severe coronavirus disease 2019 (COVID-19).
OBJECTIVES: To update data a living systematic review of the literature concerning the efficacy and toxicity of the IL-6 receptor antagonist, tocilizumab, in COVID-19 patients.
DATA SOURCES: Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus up, preprint servers and Google from October 8, 2020 till February 24, 2021.
STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) and observational studies at low or moderate risk of bias.
PARTICIPANTS: Hospitalized COVID-19 patients.
INTERVENTIONS: Tocilizumab versus placebo or standard of care.
METHODS: We pooled crude risk ratios (RRs) of RCTs with random effects model and evaluated inconsistency between studies with I2. We assessed the certainty of evidence using the GRADE approach.
RESULTS: Of 1600 citations, 8 RCTs and 28 cohorts were eligible. The 8 RCTs, at low risk of bias, with 6311 patients examined the effect of tocilizumab on short-term mortality; pooled RR was 0.91 (95%CI 0.78, 1.07, I2 = 25%). Only the REMAP-CAP and RECOVERY trials with the majority of their patients on concomitant corticosteroids, showed lower 30-day mortality with tocilizumab use, RR 0.74 (95%CI 0.59, 0.93) and 0.89 (95%CI 0.81, 0.97), respectively. Seven RCTs, with 5391 patients examined the effect of tocilizumab on risk of mechanical ventilation; pooled RR was 0.84 (95% CI 0.76, 0.93), I2 = 0%, with a corresponding number needed to treat of 20 (95%CI 14.3-33.3). Eight RCTs, with 5,340 patients, examined the effect of tocilizumab on a composite of poor outcome; pooled RR was 0.82 (95% CI 0.76, 0.90, I2 = 3%). Data from the RCTs showed a lower risk of infections and no higher risk of serious adverse events with tocilizumab; pooled RR 0.67 (95%CI 0.45, 0.99, eight RCTs) and 0.85 (95%CI 0.63, 1.16, seven RCTs), respectively. Among 28 cohorts with 15484 patients, the pooled adjusted RR for mortality was 0.53 (95%CI 0.43, 0.67, I2 = 76%).
CONCLUSIONS: Cumulative high certainty evidence shows that tocilizumab reduces the risk of mechanical ventilation in hospitalized patients with severe COVID-19. Moderate certainty evidence shows that tocilizumab reduces the risk of poor outcome and the risk of secondary infections in hospitalized COVID-19 patients. This review will continuously evaluate the role of tocilizumab in COVID-19 treatment.