Tocilizumab in hospitalized patients with COVID‐19: Clinical outcomes, inflammatory marker kinetics, and safety
Joshua A Hill, Manoj P Menon, Shireesha Dhanireddy, Mark M Wurfel, Margaret Green, Rupali Jain, Jeannie D Chan, Joanne Huang, Danika Bethune, Cameron Turtle, Christine Johnston, Hu Xie, Wendy M Leisenring, H Nina Kim, Guang‐shing Cheng
Journal of Medical Virology, doi:10.1002/jmv.26674
Coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 causes substantial morbidity. Tocilizumab, an interleukin-6 receptor antagonist, might improve outcomes by mitigating inflammation. We conducted a retrospective study of patients admitted to the University of Washington Hospital system with COVID-19 and requiring supplemental oxygen. Outcomes included clinical improvement, defined as a two-point reduction in severity on a six-point ordinal scale or discharge, and mortality within 28 days. We used Cox proportional-hazards models with propensity score inverse probability weighting to compare outcomes in patients who did and did not receive tocilizumab. We evaluated 43 patients who received tocilizumab and 45 who did not. Patients receiving tocilizumab were younger with fewer comorbidities but higher baseline oxygen requirements. Tocilizumab treatment was associated with reduced C-reactive protein, fibrinogen, and temperature, but there were no meaningful differences in time to clinical improvement (adjusted hazard ratio [aHR], 0.92; 95% confidence interval [CI], 0.38-2.22) or mortality (aHR, 0.57; 95% CI, 0.21-1.52). A numerically higher proportion of tocilizumab-treated patients had subsequent infections, transaminitis, and cytopenias. Tocilizumab did not improve outcomes in hospitalized patients with COVID-19. However, this study was not powered to detect small differences, and there remains the possibility for a survival benefit.
CONFLICT OF INTERESTS The authors declare that there are no conflict of interests.
AUTHOR CONTRIBUTIONS Joshua A. Hill, M.M., H. Nina Kim, and Guang-Shing Cheng designed the study and interpreted the data. Joshua A. Hil, M.M., Shireesha Dhanireddy, Margaret Green, Rupali Jain, Christine Johnston, Joanne Huang, and Guang-Shing Cheng contributed to data collection.
References
Aouba, Baldolli, Geffray, Targeting the inflammatory cascade with anakinra in moderate to severe COVID-19 pneumonia: case series, Ann Rheum Dis,
doi:10.1136/annrheumdis-2020-217706Campochiaro, Della-Torre, Cavalli, Efficacy and safety of tocilizumab in severe COVID-19 patients: a single-centre retrospective cohort study, Eur J Intern Med,
doi:10.1016/j.ejim.2020.05.021Capra, Rossi, Mattioli, Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia, Eur J Intern Med,
doi:10.1016/j.ejim.2020.05.009Christina, Frederick, Yu, Tocilizumab treatment for cytokine release syndrome in hospitalized COVID-19 patients: survival and clinical outcomes, Chest,
doi:10.1016/j.chest.2020.06.006Colaneri, Bogliolo, Valsecchi, Tocilizumab for treatment of severe COVID-19 patients: preliminary results from smatteo COVID-19 registry (SMACORE), Microorganisms,
doi:10.3390/microorganisms8050695Frigault, Nikiforow, Mansour, Tocilizumab not associated with increased infection risk after CAR T-implications for COVID-19?, Blood,
doi:10.1182/blood.2020006216Furong, Yuzhao, Ying, Association of inflammatory markers with the severity of COVID-19: a meta-analysis, Int J Infect Dis,
doi:10.1016/j.ijid.2020.05.055Gardner, Ceppi, Rivers, Preemptive mitigation of CD19 CAR T-cell cytokine release syndrome without attenuation of antileukemic efficacy, Blood,
doi:10.1182/blood.2019001463Geraldine, Sara, Nashla, Lewei, Daniel, Tocilizumab in rheumatoid arthritis: a meta-analysis of efficacy and selected clinical conundrums, Semin Arthritis Rheum,
doi:10.1016/j.semarthrit.2013.08.001Hay Kevin, Laïla-Aïcha, Li, Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T cell therapy, Blood,
doi:10.1182/blood-2017-06-793141Herold, Jurinovic, Arnreich, Level of IL-6 predicts respiratory failure in hospitalized symptomatic COVID-19 patients, MedRxiv,
doi:10.1101/2020.04.01.20047381Ivan, Norbert, Michael, Ronaldo, Bradley et al., Tocilizumab in hospitalized patients with COVID-19 pneumonia, MedRxiv
Lisa, Bankhead, Jeng, Mechanisms of severe acute respiratory syndrome coronavirus-induced acute lung injury, mBio,
doi:10.1128/mBio.00271-13Luca, Dennis, Profiling COVID-19 pneumonia progressing into the cytokine storm syndrome: results from a single Italian Centre study on tocilizumab versus standard of care, J Clin Virol,
doi:10.1016/j.jcv.2020.104444Masayoshi, Sho, Hiroshi, Tsukasa, Kiyoshi et al., Non-autoimmune combined factor XIII A and B subunit deficiencies in rheumatoid arthritis patients treated with antiinterleukin-6 receptor monoclonal antibody (tocilizumab), Thromb Res
Mastroianni, Greco, Apuzzo, Subcutaneous tocilizumab treatment in patients with severe COVID-19-related cytokine release syndrome: an observational cohort study, E Clin Med,
doi:10.1016/j.eclinm.2020.100410Mccaw Zachary, Tian, Jason, How to quantify and interpret treatment effects in comparative clinical studies of COVID-19, Ann Intern Med,
doi:10.7326/M20-4044Mcinnes, Thompson, Giles, Effect of interleukin-6 receptor blockade on surrogates of vascular risk in rheumatoid arthritis: MEASURE, a randomised, placebo-controlled study, Ann Rheum Dis,
doi:10.1136/annrheumdis-2013-204345Middeldorp, Coppens, Haaps, Incidence of venous thromboembolism in hospitalized patients with COVID-19, J Thromb Haemost,
doi:10.1111/jth.14888Nicola, Marcello, Donatella, Interleukin-6 receptor blockade with subcutaneous tocilizumab in severe COVID-19 pneumonia and hyperinflammation: a case-control study, Ann Rheum Dis,
doi:10.1136/annrheumdis-2020-218243Peter, Shen, Jonathan, Dexamethasone in hospitalized patients with COVID-19-preliminary report, N Engl J Med,
doi:10.1056/NEJMoa2021436Pontali, Volpi, Antonucci, Safety and efficacy of early highdose IV anakinra in severe COVID-19 lung disease, J Allergy Clin Immunol,
doi:10.1016/j.jaci.2020.05.002Roberta, Samantha, Luigi, Massimo, Prothrombotic biomarkers in patients with rheumatoid arthritis: the beneficial effect of IL-6 receptor blockade, Clin Exp Rheumatol
Rojas-Marte, Khalid, Mukhtar, Outcomes in patients with severe COVID-19 disease treated with tocilizumab: a casecontrolled study, QJM An Int J Med,
doi:10.1093/qjmed/hcaa206Rudragouda, Stanley, Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology, Semin Immunopathol,
doi:10.1007/s00281-017-0629-xSavino, Franco, Alessandra, Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in patients with severe COVID-19, Clin Exp Rheumatol
Shakoory, Joseph, Carcillo, Chatham, Interleukin-1 receptor blockade is associated with reduced mortality in sepsis patients with features of macrophage activation syndrome: reanalysis of a prior phase III trial *, Crit Care Med,
doi:10.1097/CCM.0000000000001402Somers Emily, Gregory, Jonathan, Jonathan, Tejal et al., Tocilizumab for treatment of mechanically ventilated patients with COVID-19, Clin Infect Dis,
doi:10.1101/2020.05.29.20117358Stone John, Matthew, Naomi, Efficacy of tocilizumab in patients hospitalized with COVID-19, N Engl J Med,
doi:10.1056/NEJMoa2028836Tariq, Fahrettin, Mohammed, Tocilizumab for treatment of patients with severe COVID À 19: a retrospective cohort study, E Clin Med,
doi:10.1016/j.eclinm.2020.100418Timothée, Souheil, Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients, Med Mal Infect,
doi:10.1016/j.medmal.2020.05.001Toniati, Piva, Cattalini, Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: a single center study of 100 patients in Brescia, Italy, Autoimmun Rev,
doi:10.1016/j.autrev.2020.102568Velazquez-Salinas, Verdugo-Rodriguez, Luis, Manuel, The role of interleukin 6 during viral infections, Front Microbiol,
doi:10.3389/fmicb.2019.01057Who, WHO R&D Blueprint novel coronavirus COVID-19 therapeutic trial synopsis
Wichmann, Sperhake, Lütgehetmann, Autopsy findings and venous thromboembolism in patients with COVID-19, Ann Intern Med,
doi:10.7326/m20-2003Wu, Mcgoogan, Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention, JAMA,
doi:10.1001/jama.2020.2648Yang, Wangchung, Yang, IL-6 ameliorates acute lung injury in influenza virus infection, Sci Rep,
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