Association between tocilizumab treatment and clinical outcomes of COVID-19 patients: a systematic review and meta-analysis

Abstract

To explore and summarize the association between treatment with tocilizumab and clinical outcomes in COVID-19 patients. We performed a systematic review and meta-analysis (10 RCTs including 3378 patients in the tocilizumab group and 3142 patients in the control group). We systematically searched PubMed and MedRxiv for all RCTs as of June 1, 2021, to assess the benefits and harms of tocilizumab to treat patients with COVID-19. All analyses were carried out using RevMan version 5.4.1. There were nine RCTs published in peer-reviewed journals and one RCTs published as a preprint. The summary RR for all-cause mortality with tocilizumab was 0.89 (95% CI= 0.82-0.96, P= 0.003). There was no significant between-trial heterogeneity (I 2 = 28%, P= 0.19). However, all peerreviewed RCTs showed no significant associations between treatment with tocilizumab and reductions in all-cause mortality. We notably found that tocilizumab significantly reduced the rate of intubation or death in patients with COVID-19 with 3 RCTs. Across the 8 RCTs, the summary RR for discharge with tocilizumab was 1.10 (95% CI= 1.03-1.16, P< 0.00001). There was no significant association of tocilizumab with harm on other patient-relevant clinical outcomes, including increasing secondary infection risk, patients of adverse events, or patients of serious adverse events. Tocilizumab significantly increased the rate of hospital discharges in COVID-19 patients. Still, it did not decrease all-cause mortality or increase the risk of secondary infections, patients of adverse events, or patients for serious adverse events. Evidence that tocilizumab affects clinical outcomes in patients with COVID-19 requires further proof.

Factors predicting poor outcomes of patients treated with tocilizumab for COVID‑19‑associated pneumonia: A retrospective study

“…The mortality rate found in the present study was relatively higher compared to the rates demonstrated in randomized controlled trials of tocilizumab and in meta-analyses mentioning a pooled mortality prevalence of 20-30% (17)(18)(19)(20)(21). One of the main findings of the present study was that among all patients treated with tocilizumab for COVID-19-associated pneumonia, age was the only independent factor predicting 90-day mortality.…”

New insights into development and mortality of COVID‐19‐associated pulmonary aspergillosis in a homogenous cohort of 1161 intensive care patients

“…44 Similarly, a recent systematic review and meta-analysis of clinical trials reported no significant associations between treatment with tocilizumab and reductions in all-cause mortality in COVID-19 patients. 45 Our observations and these studies together suggest that IM treatment is avoidable in CAPA as well as non-CAPA patients.…”

“…A number of randomised clinical trials have been conducted on the efficacy of IM (tocilizumab), including one at our institute, but its benefit is not yet clear 44 . Similarly, a recent systematic review and meta‐analysis of clinical trials reported no significant associations between treatment with tocilizumab and reductions in all‐cause mortality in COVID‐19 patients 45 . Our observations and these studies together suggest that IM treatment is avoidable in CAPA as well as non‐CAPA patients.…”

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] ].…”