Interleukin-6 (IL-6) inhibitors as therapeutic agents for coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis

INTRODUCTION: Preliminary studies showed that coronavirus disease 2019 (COVID-19) disrupts body immune system, including dysregulation of cytokine interleukin-6 (IL-6). IL-6 inhibitors agents have been used as treatment options for COVID-19, yet their benefit as therapeutic agents remains unclear. OBJECTIVE: We performed a systematic review and meta-analysis to synthesize the available evidence on the potential therapeutic effect of IL-6 inhibitor agents for the treatment of COVID-19. METHODS: Two authors initially screened and reviewed the relevant studies from available databases. The data extracted will be tabulated and analyzed for the outcomes. The primary outcome was mortality. Secondary outcomes included discharge from the hospital, length of stay, and requirement for mechanical ventilation. The quality of each study was assessed using OCEBM ratings. RESULTS: We reviewed 18 studies with a total of 3303 subjects. Tocilizumab was the most commonly used in the studies (15 studies). Meta-analysis of included studies revealed significant reduction in mortality with tocilizumab and sarilumab (RR = 0.61, 95% CI 0.49–0.76). Other outcomes including hospital discharge (RR = 1.04, 95% CI 0.86–1.24), length of stay (mean difference –1.96 days, 95% CI –4.24 to 0.33) or requirement for mechanical ventilation (RR = 0.68, 95% CI 0.32–1.45) revealed no differences of IL-6 inhibitor agents compared to controls. CONCLUSIONS: Available evidence suggests that IL-6 inhibitor agents reduce the risk of mortality in COVID-19, especially in severe conditions. Further well-designed trials are needed for assessing its efficacy and safety for COVID-19.