Beneficial and harmful outcomes of tocilizumab in severe COVID-19: a systematic review and meta-analysis

Abstract

Background: Pending for randomized control trials, the use of tocilizumab (TCZ) in COVID-19 is based on observational studies and remains controversial. Purpose: To summarize evidence about the effect of TCZ to treat severe COVID-19. Data sources: PubMed (via MEDLINE), Scopus, and medRxiv repository databases from 1 January to 21 August 2020. Study Selection: Observational studies in any language reporting efficacy and safety outcomes of TCZ use in hospitalized adults with COVID-19. Data Extraction: Independent, dually performed data extraction and quality assessments. Data synthesis: Of 57 eligible studies, 27 were controlled and 30 were not. The overall included patients were 8,128: 4,021 treated with TCZ, in addition to standard of care (SOC), and 4,107 only receiving SOC. The pooled mortality was lower in the TCZ-group vs. the control group, with a relative risk (RR) of 0.73 (95%CI 0.57-0.93; p=0.010). The overall NNT to avoid one death was 20. In hospital wards, patients in the TCZ-group were transferred to intensive care unit (ICU) in a higher proportion than those in the control group; however, ICU mortality of the TCZ-group was lower than in the control group. Secondary infections occurred in a higher proportion in TCZ-treated patients. Among survivors, the length of stay was similar in both groups. Limitations: Conclusions should be considered as weak evidence since they are based on observational studies, most of them retrospective. A variety of factors influencing the indication and effect of TCZ could not be evaluated in-depth. Conclusions: TCZ seems beneficial in preventing in-hospital mortality in severe, non-critically ill COVID-19 patients. Conversely, patients receiving TCZ appear to be at higher risk for secondary infections, especially those admitted to ICU.

Efficacy and safety of Tocilizumab in severe and critical COVID-19: A Systematic Review and Meta-Analysis

“…Similar results were obtained by previous meta-analysis studies on the effect of tocilizumab treatment on the mortality risk of COVID-19 patients. Khan et al [ 87 ], Rubio-Rivas et al [ 88 ], and Kotak et al [ 89 ] reported RRs [95%CIs] of 0.83 [0.72, 0.96], 0.73 [0.57, 0.93], and 0.56 [0.34, 0.92], respectively, and Zhao et al [ 90 ] and Sarfraz et al [ 91 ] reported odds ratios [95%CIs] of 0.44 [0.36, 0.55] and 0.42 [0.26, 0.69], respectively, with tocilizumab treatment compared with SOC. Despite the promising results in these meta-analysis studies, none of the four published RCTs found a significant beneficial effect on mortality rates for tocilizumab in COVID-19 patients.…”

Update in COVID-19 in the intensive care unit from the 2020 HELLENIC Athens International symposium

“…Tocilizumab which blocks IL-6 receptor is also proposed [4] with intravenous use being suggested to be superior to subcutaneous administration [42] . Although the ROCHE press release of the first results from the phase III COVACTA trial is not favouring early administration in all patients, some systematic reviews suggest potential mortality benefit in some cohorts with acute respiratory failure [43] . Sarilumab is also effective in blocking IL-6 receptors and may have similar effects.…”

Risk of Reactivation of Hepatitis B Virus (HBV) and Tuberculosis (TB) and Complications of Hepatitis C Virus (HCV) Following Tocilizumab Therapy: A Systematic Review to Inform Risk Assessment in the COVID-19 Era

“…However, based on experience from the pre-COVID era, TCZ carries a “black box” warning for serious infection events (SIEs; Figure 1B ) caused by a range of opportunistic bacterial, mycobacterial, viral and fungal pathogens that may lead to hospitalisation or death. Pooled analyses of the SIE risk associated with the standard dose have estimated incidence at ~5 per 100 patient years ( 21 , 22 ), similar to other biologic drugs ( 1 ), but with higher risk in older adults, in combination with steroids and/or methotrexate ( 23 – 25 ), or with previous biologic therapy ( 26 ). Such SIEs can be related to the impairment of IL-6 activity in co-ordinating diverse immune responses, including activation of neutrophils and lymphocytes, acute phase protein production and tissue repair ( Figure 2 ) ( 2 ).…”