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

Abstract

Introduction Preliminary study showed that coronavirus disease 2019 (COVID-19) disrupt body immune system including dysregulation of cytokine interleukin-6 (IL-6). IL-6 inhibitors agents have been used as treatment option for COVID-19, yet their benefit as therapeutic agent remain 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 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 evidences suggests that IL-6 inhibitor agents do reduce the risk of mortality in COVID-19 especially in severe disease. Further well-designed trials are needed for assessing its efficacy and safety for COVID-19

Respiratory involvement parameters in hospitalized COVID-19 patients and their association with mortality and length of stay

“…We found that the use of antibiotics, NSAIDs, steroids, convalescent plasma, IL6 inhibitors, and anticoagulants was associated with increased LOS but not with mortality. Other studies showed no difference in hospital LOS with steroid, convalescent plasma, or IL6 inhibitor use [33][34][35]. We attribute the association with increased LOS in our study to the need of staying in the hospital to complete the treatment course, which is supported by other studies [16,36].…”

Tocilizumab Treatment Reduces Mortality in Hospitalized Patients with COVID-19

“…Future studies should accordingly investigate the IL-6 receptor blockade potential of tocilizumab therapy in the context of restricting the classical IL-6 signal in critically ill COVID-19 patients. This study did not nd credible evidence concerning the clinical correlation between thromboembolic events, IL-6 levels, and deaths among patients on tocilizumab therapy, The systematic review and metaanalysis by Pinzon et al (2021) revealed a strong relationship between IL-6 inhibitor drugs and mortality reduction in the setting of COVID-19 [39]. The ndings also revealed the potential of IL-6 inhibitors (including tocilizumab) to minimize the length of hospital stay and mechanical ventilation requirements among the COVID-19 patients on tocilizumab therapy.…”

Tocilizumab Treatment Reduces Mortality in Hospitalized Patients with COVID-19

“…Future studies should accordingly investigate the IL-6 receptor blockade potential of tocilizumab therapy in the context of restricting the classical IL-6 signal in critically ill COVID-19 patients. This study did not nd credible evidence concerning the clinical correlation between thromboembolic events, IL-6 levels, and deaths among patients on tocilizumab therapy, The systematic review and meta-analysis by Pinzon et al (2021) revealed a strong relationship between IL-6 inhibitor drugs and mortality reduction in the setting of COVID-19 [38]. The ndings also revealed the potential of IL-6 inhibitors (including tocilizumab) to minimize the length of hospital stay and mechanical ventilation requirements among the COVID-19 patients on tocilizumab therapy.…”