Tocilizumab for COVID-19: real-time analysis of 50 studies

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Jun 8	Covid Analysis	Tocilizumab for COVID-19: real-time meta analysis of 46 studies
	Significantly lower risk is seen for ventilation and recovery. 20 studies from 20 independent teams in 7 countries show significant benefit. Meta analysis using the most serious outcome reported shows 8% [-8‑22%] lower risk, wi..
Mar 6	Htet et al., British Journal of Clinical Pharmacology, doi:10.1002/bcp.70025	Adverse events associated with monoclonal antibodies used for treatment of COVID‐19: A systematic review and meta‐analysis
	Systematic review and meta-analysis of 16 RCTs with 19,797 COVID-19 patients, showing a statistically significant increased risk of hepatotoxicity and neutropenia associated with monoclonal antibody (mAb) treatments compared to standard o..
Feb 10	Reid et al., NCT04479358	COVIDOSE-2: A Multi-center, Randomized, Controlled Phase 2 Trial Comparing Early Administration of Low-dose Tocilizumab to Standard of Care in Hospitalized Patients With COVID-19 Pneumonitis Not Requiring Invasive Ventilation
	2% slower recovery (p=0.94). RCT 85 patients in the USA showing no significant differences with tocilizumab treatment.
Nov 8 2024	Xie et al., Cellular & Molecular Biology Letters, doi:10.1186/s11658-024-00659-6	The role of reactive oxygen species in severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection-induced cell death
	Review of the effects of reactive oxygen species (ROS) on cell death pathways in SARS-CoV-2 infection. SARS-CoV-2 induces oxidative stress and ROS generation which can lead to several types of regulated cell death including NETosis, ferro..
Aug 20 2024	Yen et al., BMC Infectious Diseases, doi:10.1186/s12879-024-09654-w	Predictors for cause-specific and timing of deaths in patients with COVID-19: a cohort study in Taiwan
	58% higher mortality (p=0.06). Retrospective 2,196 COVID-19 patients in Taiwan (49% mild cases, 44% moderate, 7% severe) showing higher mortality with tocilizumab, without statistical significance.
Feb 20 2024	Talaschian et al., Iranian Journal of Allergy, Asthma and Immunology, doi:10.18502/ijaai.v23i1.14956	Tocilizumab Failed to Reduce Mortality in Severe COVID-19 Patients: Results from a Randomized Controlled Clinical Trial
	40% higher mortality (p=0.71), 47% higher hospital discharge (p=0.26), and 40% worse recovery (p=0.71). RCT 40 hospitalized COVID-19 patients in Iran showing no significant improvement in mortality, clinical outcomes, or oxygen therapy requirements with tocilizumab treatment. The study found no significant differences between the tocilizuma..
Nov 20 2023	Ghaempanah et al., Journal of Pharmaceutical Policy and Practice, doi:10.1186/s40545-023-00662-w	Does tocilizumab have an effect on the clinical outcomes in COVID-19 patients? A meta-analysis of randomized control trials
	Meta-analysis of 17 RCTs showing no significant differences with tocilizumab treatment.
Oct 31 2023	Ho et al., HCA Healthcare Journal of Medicine, doi:10.36518/2689-0216.1546	A Retrospective Cohort Study Assessing the Impact of Statin Therapy on Hospital Length of Stay and Inpatient Mortality in COVID-19 Patients
	290% higher mortality (p<0.0001). Retrospective 26,445 hospitalized COVID-19 patients in the USA, showing higher mortality with tocilizumab.
Feb 3 2022	Hermine et al., European Respiratory Journal, doi:10.1183/13993003.02523-2021	Effect of interleukin-6 receptor antagonists in critically ill adult patients with COVID-19 pneumonia: two randomised controlled trials of the CORIMUNO-19 Collaborative Group
	33% lower mortality (p=0.33). Two open-label RCTs of 97 and 91 critically ill COVID-19 patients in France showing no significant differences with tocilizumab or sarilumab.
May 31 2021	Horby et al., The Lancet, doi:10.1016/S0140-6736(21)00676-0	Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
	12% lower mortality (p=0.005), 21% lower ventilation (p=0.002), and 14% higher hospital discharge (p<0.0001). RCT 4,116 hospitalized COVID-19 patients showing significantly lower mortality with tocilizumab.
May 31 2021	Soin et al., The Lancet Respiratory Medicine, doi:10.1016/S2213-2600(21)00081-3	Tocilizumab plus standard care versus standard care in patients in India with moderate to severe COVID-19-associated cytokine release syndrome (COVINTOC): an open-label, multicentre, randomised, controlled, phase 3 trial
	29% lower mortality (p=0.4), 4% higher ventilation (p=1), 30% lower progression (p=0.47), and 7% higher ICU admission (p=0.49). RCT 180 hospitalized patients with moderate to severe COVID-19 in India showing no significant difference in disease progression with tocilizumab.
May 1 2021	De Rosa et al., Journal of Clinical Medicine, doi:10.3390/jcm10091951	Risk Factors for Mortality in COVID-19 Hospitalized Patients in Piedmont, Italy: Results from the Multicenter, Regional, CORACLE Registry
	41% higher mortality (p=0.38). Retrospective 1,538 hospitalized patients in Italy, showing only HCQ associated with reduced mortality. Authors analyze mortality amongst those that were alive at day 7 to avoid survival time bias due to drug recording requiring a minimum..
Apr 30 2021	Huang et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.02.057	Tocilizumab treatment in critically ill patients with COVID-19: A retrospective observational study
	Retrospective 96 critically ill COVID-19 patients showing lower mortality with tocilizumab in unadjusted results, however the groups are not comparable, for example the tocilizumab group was significantly more likely to be treated with HC..
Apr 26 2021	Mohandas et al., Clinical Epidemiology and Global Health, doi:10.1016/j.cegh.2021.100751	Clinical review of COVID-19 patients presenting to a quaternary care private hospital in South India: A retrospective study
	429% higher mortality (p<0.0001). Retrospective 3,345 hospitalized patients in India, showing higher mortality with remdesivir and tocilizumab in unadjusted results. Confounding by indication is likely.
Apr 22 2021	Gordon et al., New England Journal of Medicine, doi:10.1056/NEJMoa2100433	Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19
	22% lower mortality (p=0.03). RCT 803 critically ill COVID-19 patients showing improved outcomes with tocilizumab and sarilumab. There was only 48 sarilumab patients and the model used shrinks the posterior distribution for each intervention effect toward the overall ..
Apr 22 2021	Rosas et al., New England Journal of Medicine, doi:10.1056/NEJMoa2028700	Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia
	1% higher mortality (p=1), 24% lower ventilation (p=0.16), 41% lower ICU admission (p=0.04), and 22% faster recovery (p=0.18). RCT 452 hospitalized patients with severe COVID-19 pneumonia showing no significant difference in clinical status or mortality at day 28 with tocilizumab. There was significantly lower ICU admission for patients not in the ICU at baseline.
Feb 28 2021	Rodríguez-Baño et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.08.010	Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)
	78% lower mortality (p=0.04) and 58% lower combined mortality/intubation (p=0.03). Retrospective 778 hospitalized COVID-19 patients with hyperinflammatory state showing tocilizumab associated with lower mortality. The 1:2 PSM analysis may be the most accurate because it provides documented, tight covariate balance acros..
Feb 28 2021	Martínez-Sanz et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2020.09.021	Effects of tocilizumab on mortality in hospitalized patients with COVID-19: a multicentre cohort study
	35% lower mortality (p=0.51). Retrospective 1,229 hospitalized COVID-19 patients in Spain showing that tocilizumab was associated with decreased mortality in patients with high C-reactive protein (CRP) levels (>150 mg/L) but not in those with lower CRP levels.
Feb 28 2021	Fisher et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.12.021	Tocilizumab in the treatment of critical COVID-19 pneumonia: A retrospective cohort study of mechanically ventilated patients
	4% higher mortality (p=0.96). Retrospective 115 mechanically ventilated COVID-19 patients showing no mortality benefit with tocilizumab treatment.
Jan 20 2021	Veiga et al., BMJ, doi:10.1136/bmj.n84	Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial
	130% higher mortality (p=0.09) and 1% improved recovery (p=0.96). RCT 129 hospitalized patients with severe or critical COVID-19 in Brazil showing no benefit and potential harm with tocilizumab treatment.
Jan 7 2021	Salama et al., New England Journal of Medicine, doi:10.1056/NEJMoa2030340	Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia
	22% higher mortality (p=0.72) and 44% lower combined mortality/intubation (p=0.03). RCT 377 hospitalized COVID-19 patients with pneumonia showing that tocilizumab significantly reduced mechanical ventilation or death by day 28, however there was no difference in mortality alone.
Jan 1 2021	Hermine et al., JAMA Internal Medicine, doi:10.1001/jamainternmed.2020.6820	Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia
	7% lower mortality (p=1), 62% lower ventilation (p=0.05), and 34% lower progression (p=0.18). RCT 130 hospitalized COVID-19 patients with moderate or severe pneumonia showing tocilizumab did not reduce WHO-CPS scores below 5 at day 4 (primary outcome), but reduced the proportion of patients needing noninvasive ventilation, high-fl..
Jan 1 2021	Salvarani et al., JAMA Internal Medicine, doi:10.1001/jamainternmed.2020.6615	Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia
	110% higher mortality (p=0.61), 26% higher ICU admission (p=0.76), and 26% lower hospital discharge (p=0.76). RCT 126 hospitalized COVID-19 patients with pneumonia showing no significant benefit of tocilizumab treatment.
Jan 1 2021	Gupta et al., JAMA Internal Medicine, doi:10.1001/jamainternmed.2020.6252	Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19
	29% lower mortality (p=0.007). Retrospective 3,924 critically ill COVID-19 patients showing lower mortality with tocilizumab.
Dec 31 2020	Wang et al., SSRN Electronic Journal, doi:10.2139/ssrn.3667681	Tocilizumab Ameliorates the Hypoxia in COVID-19 Moderate Patients with Bilateral Pulmonary Lesions: A Randomized, Controlled, Open-Label, Multicenter Trial
	27% lower progression (p=0.53), 8% longer hospitalization (p=0.35), and 6% slower viral clearance (p=0.54). RCT 65 COVID-19 patients in China showing improvement in hypoxia recovery with tocilizumab treatment, especially in moderate patients with bilateral pulmonary lesions.
Dec 10 2020	Stone et al., New England Journal of Medicine, doi:10.1056/NEJMoa2028836	Efficacy of Tocilizumab in Patients Hospitalized with Covid-19
	52% higher mortality (p=0.54), 35% lower ventilation (p=0.36), 17% lower combined mortality/intubation (p=0.65), and 11% higher progression (p=0.76). RCT 243 hospitalized patients with COVID-19 showing no significant difference in intubation or death with tocilizumab compared to placebo. Authors hypothesize that elevated interleukin-6 levels may represent host responses to infection ra..
Dec 6 2020	Ruiz-Antorán et al., Infectious Diseases and Therapy, doi:10.1007/s40121-020-00373-8	Combination of Tocilizumab and Steroids to Improve Mortality in Patients with Severe COVID-19 Infection: A Spanish, Multicenter, Cohort Study
	26% lower mortality (p=0.001). Retrospective 506 hospitalized COVID-19 patients in Spain showing lower mortality with tocilizumab.
Nov 30 2020	Canziani et al., Journal of Autoimmunity, doi:10.1016/j.jaut.2020.102511	Interleukin-6 receptor blocking with intravenous tocilizumab in COVID-19 severe acute respiratory distress syndrome: A retrospective case-control survival analysis of 128 patients
	18% lower mortality (p=0.57). Retrospective case-control study of 128 hospitalized COVID-19 patients with severe respiratory impairment showing no significant difference in 30-day mortality with intravenous tocilizumab treatment.
Nov 22 2020	Hill et al., Journal of Medical Virology, doi:10.1002/jmv.26674	Tocilizumab in hospitalized patients with COVID‐19: Clinical outcomes, inflammatory marker kinetics, and safety
	43% lower mortality (p=0.27) and 8% greater improvement (p=0.86). Retrospective 88 hospitalized COVID-19 patients showing no significant difference in clinical improvement or mortality with tocilizumab treatment.
Nov 14 2020	Roumier et al., Journal of Clinical Immunology, doi:10.1007/s10875-020-00911-6	Tocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis
	32% lower mortality (p=0.34), 42% lower ventilation (p=0.03), and 45% higher hospital discharge (p=0.03). Prospective analysis of 96 hospitalized patients with severe worsening COVID-19 pneumonia showing that tocilizumab treatment was associated with reduced need for ventilatory support and shorter time to oxygen withdrawal, however there wa..
Nov 5 2020	Tsai et al., Scientific Reports, doi:10.1038/s41598-020-76187-y	Impact of tocilizumab administration on mortality in severe COVID-19
	no change in mortality (p=1). PSM retrospective 274 hospitalized COVID-19 patients showing no difference in mortality with tocilizumab.
Oct 31 2020	Biran et al., The Lancet Rheumatology, doi:10.1016/S2665-9913(20)30277-0	Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study
	29% lower mortality (p=0.004). Retrospective 764 COVID-19 patients requiring ICU support showing lower mortality with tocilizumab. There was significantly higher use of HCQ+AZ in the treatment group, which was not adjusted for in the propensity score matching or Cox re..
Oct 31 2020	Langer-Gould et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.07.081	Early identification of COVID-19 cytokine storm and treatment with anakinra or tocilizumab
	117% higher mortality (p=0.53). Retrospective 93 hospitalized COVID-19 patients with cytokine storm showing no significant difference between anakinra and tocilizumab treatment after adjusting for baseline characteristics.
Oct 31 2020	Masiá et al., EBioMedicine, doi:10.1016/j.ebiom.2020.102999	Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort study
	80% lower mortality (p=0.04), 8% lower ICU admission (p=1), 44% longer hospitalization (p=0.0004), and 68% worse viral clearance (p=0.51). Prospective cohort study of 138 hospitalized COVID-19 patients showing lower mortality with tocilizumab.
Oct 28 2020	Kimmig et al., Frontiers in Medicine, doi:10.3389/fmed.2020.583897	IL-6 Inhibition in Critically Ill COVID-19 Patients Is Associated With Increased Secondary Infections
	82% higher mortality (p=0.09). Retrospective 111 critically ill COVID-19 patients showing that tocilizumab treatment was associated with increased secondary bacterial infections, higher mortality (35.2% vs 19.3%, p=0.020), and a trend toward more fungal infections (5.6..
Oct 24 2020	Chilimuri et al., Journal of Clinical Pharmacy and Therapeutics, doi:10.1111/jcpt.13303	Tocilizumab use in patients with moderate to severe COVID‐19: A retrospective cohort study
	60% lower combined mortality/intubation (p=0.008). Retrospective 1,225 hospitalized patients showing lower mortality/intubation with tocilizumab.
Oct 20 2020	Patel et al., Journal of Internal Medicine, doi:10.1111/joim.13163	Use of the IL‐6R antagonist tocilizumab in hospitalized COVID‐19 patients
	9% lower mortality (p=0.8). Retrospective 42 hospitalized COVID-19 patients treated with tocilizumab showing no significant differences in mortality compared to matched controls.
Oct 17 2020	Rossi et al., Pharmaceuticals, doi:10.3390/ph13100317	Effect of Tocilizumab in Hospitalized Patients with Severe COVID-19 Pneumonia: A Case-Control Cohort Study
	64% lower mortality (p=0.003) and 60% lower combined mortality/intubation (p=0.001). Retrospective 246 hospitalized patients with severe COVID-19 pneumonia showing significantly lower mortality with tocilizumab treatment.
Oct 15 2020	Guisado-Vasco et al., eClinicalMedicine, doi:10.1016/j.eclinm.2020.100591	Clinical characteristics and outcomes among hospitalized adults with severe COVID-19 admitted to a tertiary medical center and receiving antiviral, antimalarials, glucocorticoids, or immunomodulation with tocilizumab or cyclosporine: A retrospective observational study (COQUIMA cohort)
	140% higher mortality (p=0.02). Retrospective 607 patients showing higher mortality with tocilizumab use.
Oct 5 2020	Okoh et al., Journal of Medical Virology, doi:10.1002/jmv.26471	Tocilizumab use in COVID‐19‐associated pneumonia
	167% higher mortality (p=0.21) and 344% higher ICU admission (p=0.01). PSM retrospective 77 hospitalized patients receiving tocilizumab treatment and matched controls, showing no significant difference in outcomes.
Sep 29 2020	Menzella et al., Critical Care, doi:10.1186/s13054-020-03306-6	Efficacy of tocilizumab in patients with COVID-19 ARDS undergoing noninvasive ventilation
	45% lower mortality (p=0.19) and 56% lower combined mortality/intubation (p=0.02). Retrospective 79 COVID-19 patients with ARDS undergoing noninvasive ventilation showing lower risk of intubation or death with tocilizumab treatment.
Aug 31 2020	Guaraldi et al., The Lancet Rheumatology, doi:10.1016/S2665-9913(20)30173-9	Tocilizumab in patients with severe COVID-19: a retrospective cohort study
	62% lower mortality (p=0.02) and 39% lower combined mortality/intubation (p=0.02). Retrospective 544 patients with severe COVID-19 pneumonia showing lower mechanical ventilation or death with tocilizumab.
Aug 21 2020	Pettit et al., Journal of Medical Virology, doi:10.1002/jmv.26429	Late onset infectious complications and safety of tocilizumab in the management of COVID‐19
	71% higher mortality (p=0.05). Retrospective 74 hospitalized COVID-19 patients treated with tocilizumab and 74 matched controls, showing higher mortality with tocilizumab.
Jul 31 2020	Kewan et al., eClinicalMedicine, doi:10.1016/j.eclinm.2020.100418	Tocilizumab for treatment of patients with severe COVID–19: A retrospective cohort study
	40% lower hospital discharge (p=0.27), 30% shorter ventilation (p=0.16), and 57% longer hospitalization (p=0.16). Retrospective 51 hospitalized COVID-19 patients showing significant reduction in vasopressor support duration with tocilizumab treatment, but no significant difference in other outcomes.
Jul 31 2020	Gokhale et al., eClinicalMedicine, doi:10.1016/j.eclinm.2020.100467	Tocilizumab improves survival in patients with persistent hypoxia in severe COVID-19 pneumonia
	38% lower mortality (p=0.05). Retrospective cohort study of 161 hospitalized patients with severe COVID-19 pneumonia and persistent hypoxia showing survival benefit with tocilizumab.
Jul 28 2020	Maeda et al., Journal of Medical Virology, doi:10.1002/jmv.26365	The association of interleukin‐6 value, interleukin inhibitors, and outcomes of patients with COVID‐19 in New York City
	no change in mortality (p=1). Retrospective 224 hospitalized COVID-19 patients in the USA, showing no significant difference in mortality with tocilizumab.
Jul 15 2020	Carvalho et al., medRxiv, doi:10.1101/2020.07.13.20149328	Effects of Tocilizumab in Critically Ill Patients With COVID-19: A Quasi-Experimental Study
	166% higher mortality (p=0.3). Retrospective 53 critically ill COVID-19 patients showing no difference in mortality, need for renal replacement therapy, use of antibiotics, or positive cultures with tocilizumab treatment.
Jul 11 2020	Somers et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa954	Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19
	45% lower mortality (p=0.02). Retrospective 154 mechanically ventilated COVID-19 patients showing improved survival with tocilizumab. However, tocilizumab was associated with significantly higher rates of superinfection, particularly ventilator-associated pneumonia.
Jun 30 2020	Campochiaro et al., European Journal of Internal Medicine, doi:10.1016/j.ejim.2020.05.021	Efficacy and safety of tocilizumab in severe COVID-19 patients: a single-centre retrospective cohort study
	53% lower mortality (p=0.15), 27% higher hospital discharge (p=0.32), and 21% greater improvement (p=0.61). \Retrospective 65 severe COVID-19 patients showing no statistically significant differences with tocilizumab.
Jun 19 2020	Rojas-Marte et al., QJM: An International Journal of Medicine, doi:10.1093/qjmed/hcaa206	Outcomes in patients with severe COVID-19 disease treated with tocilizumab: a case–controlled study
	21% lower mortality (p=0.11). Retrospective case-control study of 193 hospitalized COVID-19 patients showing a non-statistically significant trend toward lower mortality with tocilizumab treatment. When excluding intubated patients, tocilizumab was associated with sig..
May 25 2020	Ip et al., PLoS ONE, doi:10.1371/journal.pone.0237693	Hydroxychloroquine and Tocilizumab Therapy in COVID-19 Patients - An Observational Study
	24% lower mortality (p=0.06). Retrospective 2,512 hospitalized patients showing lower mortality with tocilizumab treatment within a subset of ICU patients, 143 treated with tocilizumab with adequate data, and 413 control patients.
May 9 2020	Colaneri et al., Microorganisms, doi:10.3390/microorganisms8050695	Tocilizumab for Treatment of Severe COVID-19 Patients: Preliminary Results from SMAtteo COvid19 REgistry (SMACORE)
	18% lower mortality (p=0.85) and 88% lower ICU admission (p=0.43). PSM retrospective 112 hospitalized COVID-19 patients showing no significant difference in ICU admission or mortality with tocilizumab.

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