Tocilizumab Effect in COVID-19 Hospitalized Patients: A Systematic Review and Meta-Analysis of Randomized Control Trials

Author(s): Basheer Abdulrahman, Waleed Th Aletreby, Ahmed F Mady, Alfateh Mohammed Noor, Mohammed Lhmdi, Fahad Faqihi, Abdulrahman M Alharthy, Mohammed A Al-Odat, Dimitrios Karakitsos, Ziad A Memish

Since the emergence of the first cases of COVID-19 viral pneumonia late 2019 several studies evaluated the benefits of different treatment modalities. Early in the pandemic, the interleukin 6 (IL-6) receptor antibody Tocilizumab was considered in view of the cytokine release syndrome associated with COVID-19 infection. Several early observational studies showed beneficial effect of treatment with Tocilizumab on mortality, however, results from well-designed randomized clinical trials (RCT) were contradicting.

Objectives: To perform a systematic literature review and meta-analysis of RCTs utilizing Tocilizumab in the treatment of COVID-19 pneumonia, with in-hospital mortality as a primary objective, while secondary objectives included composite outcome of mortality, intubation, or ICU admission, another secondary outcome was super added infection.

Method: This was a random effects model (DerSimonian and Laird) model of relative risk (RR), along with corresponding 95% confidence intervals, p values, and forest plots of both primary and secondary outcomes. A fixed effect sensitivity test was performed for the primary outcome, in addition to subgroup and meta-regression analyses with predefined criteria.

Results: The primary outcome of mortality showed statistically insignificant reduction of mortality with Tocilizumab (RR = 0.9, 95% CI: 0.8 – 1.01; p = 0.09) although with an unmistakable apparent clinical benefit. There was a significant reduction in the RR of the secondary composite outcome (RR = 0.83, 95% CI: 0.76 – 0.9; p < 0.001), and no difference between groups in super-added infection (RR = 0.77, 95% CI: 0.51 – 1.19; p = 0.24). Treatment protocol allowing a second dose was the only significant predictor of improved mortality in the meta-regression analysis. Certainty of evidence was reduced to moderate for the primary outcome and the secondary outcome of clin