Tocilizumab for COVID-19: A systematic review and meta-analysis of randomized controlled trials

Abstract

The effective treatment modalities for severe coronavirus disease 2019 (COVID-19) are needed. As the primary cause of mortality is a hyperinflammatory state, the interleukin-6 antagonist tocilizumab has been used in multiple clinical studies. We conducted this systematic review and meta-analysis to estimate the effectiveness of tocilizumab in reduction of mortality due to COVID-19. A systematic search of the Pubmed and Embase databases was performed to extract randomized controlled trials (RCTs) regarding the use of tocilizumab therapy for COVID-19. An overall pooled mortality analysis was performed, and odds ratios were reported. Cochrane risk of bias assessment tool was used to assess the risk of bias. Heterogeneity was assessed using the I2 statistic. Nine RCTs, including 6489 patients, were selected for meta-analysis. Seven trials reported 28-day mortality, and one trial each reported 21-day and 30-day mortality. There were 846 deaths among 3358 participants in the steroid group while 943 deaths among 3131 patients randomized to the control group (random-effects odds ratio 0.87, 95% confidence interval 0.73-1.03, p=0.11). There was some heterogeneity among the trials as the I2 value was 15%, with a p-value of 0.31. There was a reduction in the need for ICU admission in the tocilizumab group. A higher risk of secondary infections was noted in the tocilizumab group (fixed-effects odds ratio 0.72, 95% confidence interval 0.55-0.95, p=0.02). This meta-analysis of RCTs demonstrated that the use of tocilizumab was not associated with a reduction in all-cause mortality in patients with COVID-19 and had higher odds of secondary infections.

Identification of Distinct Clinical Phenotypes of Critically Ill COVID-19 Patients: Results from a Cohort Observational Study

“…Pinpointing these isolated biomarkers as therapeutical targets may be insufficient to address all the inflammatory and mechanisms active in these patients. Furthermore, the prognostic value of this biomarker may be underlined in a more complex inflammatory profile, dependent on patient's immunological variables, and subject to a different prevalence of these clinical phenotypes [49][50][51][52].…”

Association between tocilizumab treatment of hyperinflammatory patients with COVID-19 in a critical care setting and elevated incidence of hospital-acquired bacterial and invasive fungal infections

“…Studies of Tocilizumab in COVID-19 have given conflicting results, which may reflect lack of standard protocols for its use [ [16] , [17] , [18] , [19] , [20] ]. Initial trials demonstrated no clear benefit of Tocilizumab monotherapy on survival, length of hospital stay, need for mechanical ventilation, disease progression or time to recovery [ [21] , [22] , [23] , [24] , [25] , [26] ].…”

Targeted Therapy in Rheumatoid-Arthritis-Related Interstitial Lung Disease

“…The authors report that while their meta-analysis highlights a significant improvement in the FVC after one year of RTX treatment, the trend towards an improvement in DLCO is not statistically significant. They conclude that there remains an urgent need for further studies, including RCTs comparing the effectiveness of RTX against other immunosuppressants [27].…”