Tocilizumab for treating COVID-19: a systemic review and meta-analysis of retrospective studies

Zhao, Meng; Lu, Jiuwei; Tang, Yihu; Dai, Yawei; Zhou, Jingxin; Wu, Yanhu

doi:10.1007/s00228-020-03017-5

Cited by 30 publications

(43 citation statements)

References 38 publications

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“…Lan et al showed that tocilizumab could not provide additional benefits for clinical outcomes of severe COVID-19, but the mortality rate was lower than the SOC, although this was not statistically different 10 . Studies from Kaye et al, Zhao, J et al, and Zhao, M et al, reported that tocilizumab showed a statistically significant reduction in mortality and fatality than the SOC, similar to our results 9,11,13 .…”

Section: Discussionsupporting

confidence: 92%

“…Meta-analysis on this topic has not been previously conducted; only mortality events and ICU admissions have been reported by previous studies [9][10][11]13 . In our study, we evaluate all-cause mortality events, length of stay in hospital, and days until death (time to death after first intervention) and carry out subgroup analysis of baseline criteria for administration of tocilizumab treatment.…”

Section: Strengths and Limitations Of The Analysismentioning

confidence: 99%

“…Several retrospective case-control, single-armed studies and randomized clinical trials declared promising results of tocilizumab treatment in SARS CoV-2 infection. Nevertheless, some systematic reviews and meta-analyses showed an unclear risk of bias and reported debatable results about tocilizumab's benefit as a treatment 6,[8][9][10][11][12][13] . We performed a systematic review and meta-analysis to research the risks and benefits of tocilizumab and investigate outcomes from different baseline criteria for administration of tocilizumab as a treatment for severe and critically ill COVID-19 patients.…”

Section: Introductionmentioning

confidence: 99%

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Optimal use of tocilizumab for severe and critical COVID-19: a systematic review and meta-analysis

et al. 2021

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Background: Several studies have revealed the potential use of tocilizumab in treating COVID-19 since no therapy has yet been approved for COVID-19 pneumonia. Tocilizumab may provide clinical benefits for cytokine release syndrome in COVID-19 patients. Methods: We searched for relevant studies in PubMed, Embase, Medline, and Cochrane published from March to October 2020 to evaluate optimal use and baseline criteria for administration of tocilizumab in severe and critically ill COVID-19 patients. Research involving patients with confirmed SARS-CoV-2 infection, treated with tocilizumab and compared with the standard of care (SOC) was included in this study. We conducted a systematic review to find data about the risks and benefits of tocilizumab and outcomes from different baseline criteria for administration of tocilizumab as a treatment for severe and critically ill COVID-19 patients. Results: A total of 26 studies, consisting of 23 retrospective studies, one prospective study, and two randomised controlled trials with 2112 patients enrolled in the tocilizumab group and 6160 patients in the SOC group, were included in this meta-analysis. Compared to the SOC, tocilizumab showed benefits for all-cause mortality events and a shorter time until death after first intervention but showed no difference in hospital length of stay. Upon subgroup analysis, tocilizumab showed fewer all-cause mortality events when CRP level ≥100 mg/L, P/F ratio 200-300 mmHg, and P/F ratio <200 mmHg. However, tocilizumab showed a longer length of stay when CRP <100 mg/L than the SOC. Conclusion: This meta-analysis demonstrated that tocilizumab has a positive effect on all-cause mortality. It should be cautiously administrated for optimal results and tailored to the patient's eligibility criteria.

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Section: Discussionsupporting

confidence: 92%

Section: Strengths and Limitations Of The Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Optimal use of tocilizumab for severe and critical COVID-19: a systematic review and meta-analysis

et al. 2021

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Rezaei

Fatemi

Majd

et al. 2021

Expert Review of Clinical Immunology

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Objectives Currently published papers and clinical guidelines regarding the effects of tocilizumab in severe and critical COVID-19 are contradictory. The aim of this meta-analysis was to combine the results of clinical studies of different designs to investigate the efficacy and safety of tocilizumab in severely-to-critically ill COVID-19 patients. Methods A systematic search was performed in PubMed, Embase, CENTRAL, ClinicalTrials.gov, Scopus, and preprint servers up to 26 December 2020. Since a substantial heterogeneity was expected, a random-effects model was applied to calculate the pooled effect size (ES) and 95% confidence interval (CI) for each study outcome. Results Forty-five comparative studies involving 13,189 patients and 28 single-arm studies involving 1,770 patients were analyzed. The risk of mortality (RR of 0.76 [95%CI 0.65 to 0.89], P < 0.01) and intubation (RR of 0.48 [95%CI 0.24 to 0.97], P = 0.04) were lower in tocilizumab patients compared with controls. We did not find any significant difference in secondary infections, length of hospital stay, hospital discharge before day 14, and ICU admission between groups. Conclusion Tocilizumab can improve clinical outcomes and reduce mortality rates in severe to critical COVID-19 patients. Large-scale randomized controlled trials are still required to improve the statistical power of meta-analysis.

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“… 37 , 38 , 39 , 40 An open-label study showed that tocilizumab could be safe and effective in patients in hospital with severe COVID-19, especially when applying strict selection criteria on the basis of clinical and laboratory inflammatory profiling, such as C-reactive protein, D-dimer, ferritin and lactate dehydrogenase concentrations. 40 Further data from systematic reviews and meta-analyses, including retrospective case-control studies and single-armed studies, 41 , 42 , 43 , 44 , 45 , 46 , 47 supported the addition of tocilizumab to standard of care to reduce mortality in severe COVID-19 cases.…”

Section: Antirheumatic Drugs For the Management Of Covid-19mentioning

confidence: 99%

The role of antirheumatics in patients with COVID-19

Nissen

Sciascia

Andrade

et al. 2021

The Lancet Rheumatology

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The COVID-19 pandemic has resulted in more than 2 million deaths globally. Two interconnected stages of disease are generally recognised; an initial viral stage and a subsequent immune response phase with the clinical characteristics of hyperinflammation associated with acute respiratory distress syndrome. Therefore, many immune modulators and immunosuppressive drugs, which are widely used in rheumatological practice, have been proposed as treatments for patients with moderate or severe COVID-19. In this Review, we provide an overview of what is currently known about the efficacy and safety of antirheumatic therapies for the treatment of patients with COVID-19. Dexamethasone has been shown to reduce COVID-19 related mortality, interleukin-6 inhibitors to reduce risk of cardiovascular or respiratory organ support, and baricitinib to reduce time to recovery in hospitalised patients requiring oxygen support. Further studies are needed to identify whether there is any role for glucocorticoids in patients with less severe COVID-19. Although evidence on the use of other antirheumatic drugs has suggested some benefits, results from adequately powered clinical trials are urgently needed. The heterogeneity in dosing and the absence of uniform inclusion criteria and defined stage of disease studied in many clinical trials have affected the conclusions and comparability of trial results. However, after the success of dexamethasone in proving the anti-inflammatory hypothesis, the next 12 months will undoubtedly bring further clarity about the clinical utility and optimal dose and timing of other anti-rheumatic drugs in the management of COVID-19.

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Tocilizumab for treating COVID-19: a systemic review and meta-analysis of retrospective studies

Cited by 30 publications

References 38 publications

Optimal use of tocilizumab for severe and critical COVID-19: a systematic review and meta-analysis

Optimal use of tocilizumab for severe and critical COVID-19: a systematic review and meta-analysis

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

The role of antirheumatics in patients with COVID-19

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