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Review

Tocilizumab for the treatment of non‐critical COVID‐19 pneumonia: an overview of the rationale and clinical evidence to date

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Pages 1279-1287 | Received 16 Apr 2021, Accepted 25 Jun 2021, Published online: 26 Jul 2021

References

  • Nishimoto N, Terao K, Mima T, et al. Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood. 2008;112:3959–3964.
  • Rincon M. Interleukin-6: from an inflammatory marker to a target for inflammatory diseases. Trends Immunol. 2012;33:571–577.
  • Schneider C, Borvendég J Assessment report For RoActemra. Eur Med Agency. 2009;1–66.
  • Heink S, Yogev N, Garbers C, et al. Trans-presentation of interleukin-6 by dendritic cells is required for priming pathogenic T H 17 cells. Nat Immunol. 2017;18:74–85.
  • Kang S, Tanaka T, Narazaki M, et al. Targeting Interleukin-6 Signaling in Clinic. Immunity. 2019;50:1007–1023.
  • Singh JA, Beg S, Lopez MA. Tocilizumab for rheumatoid arthritis: a cochrane systematic review. J Rheumatol. 2011;38:10–20.
  • De Benedetti F, Brunner HI, Ruperto N, et al. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367:2385–2395.
  • Villiger PM, Adler S, Kuchen S, et al. Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2016;387:1921–1927.
  • Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124:188–195.
  • Tanaka T, Narazaki M, Kishimoto T. Immunotherapeutic implications of IL-6 blockade for cytokine storm. Immunotherapy. 2016;8:959–970.
  • Maude SL, Frey N, Shaw PA, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371:1507–1517.
  • Docherty AB, Harrison EM, Green CA, et al. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO clinical characterisation protocol: prospective observational cohort study. BMJ. 2020;369:1–19.
  • Kenny G, Mallon PW. COVID19- clinical presentation and therapeutic considerations. Biochem Biophys Res Commun. 2021;538:125–131.
  • Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062.
  • Rojatti M, Ib R, Zanforlin A, et al. Lung ultrasound and respiratory pathophysiology in mechanically ventilated COVID-19 patients-an observational trial. SN Compr Clin Med [Internet]. 2020;1–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32995708
  • Lee JS, Park S, Jeong HW, et al. Immunophenotyping of covid-19 and influenza highlights the role of type i interferons in development of severe covid-19. Sci Immunol. 2020;5(49).
  • National Health Commission. Diagnosis and treatment protocol for novel coronavirus pneumonia (Trial version 7). Chin Med J (Engl) [Internet]. 2020;133:1087–1095. Available from: https://www.who.int/docs/default-source/wpro---documents/countries/china/covid-19-briefing-nhc/1-clinical-protocols-for-the-diagnosis-and-treatment-of-covid-19-v7.pdf?sfvrsn=c6cbfba4_2
  • Pennica A, Conforti G, Falangone F, et al. Clinical management of adult coronavirus infection disease 2019 (COVID-19) positive in the setting of low and medium intensity of care: a short practical review. SN Compr Clin Med [Internet]. 2020;1–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32838135
  • Toniati P, Piva S, Cattalini M, et al. 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. J Infect. 2020;19(7):1568-9972.
  • Rojas-Marte G, Khalid M, Mukhtar O, et al. Outcomes in patients with severe COVID-19 disease treated with tocilizumab: a case-controlled study. Qjm. 2020;113:546–550.
  • Somers E, Eschenauer G, Troost JP, et al. Tocilizumab for treatment of mechanically ventilated patients with COVID-19. Clin Infect Dis. 2020;ciaa954:1–31.
  • Potere N, Di Nisio M, Cibelli D, et al. Interleukin-6 receptor blockade with subcutaneous tocilizumab in severe COVID-19 pneumonia and hyperinflammation: a case-control study. Ann Rheum Dis. 2021;80:271–272.
  • Martínez-Urbistondo D, Costa Segovia R, Suárez del Villar Carrero R, et al. Early combination of tocilizumab and corticosteroids: an upgrade in anti-inflammatory therapy for severe coronavirus disease (COVID). Clin Infect Dis. 2020;72(9):1–2.
  • McCarthy C, Savinelli S, Feeney ER, et al. Tocilizumab therapy in individuals with COVID-19 infection and hyperinflammatory state. Respirology. 2020;25(10):1090-1094.
  • Ramanathan K, Antognini D, Combes A, et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol. 2020;2(8):19–21.
  • Guaraldi G, Meschiari M, Cozzi-Lepri A, et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol [Internet]. 2020;2:e474–e484. Available from: https://linkinghub.elsevier.com/retrieve/pii/S2665991320301739
  • Gupta S, Wang W, Hayek SS, et al. Association between early treatment with tocilizumab and mortality among critically ill patients with COVID-19. JAMA Intern Med. 2021;181:41.
  • Colaneri M, Bogliolo L, Valsecchi P, et al. Tocilizumab for treatment of severe COVID-19 patients: preliminary results from SMAtteo COvid19 REgistry (SMACORE). Microorganisms [Internet]. 2020;8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32397399
  • Kimmig LM, Wu D, Gold M, et al. IL-6 inhibition in critically ill COVID-19 patients is associated with increased secondary infections. Front Med [Internet]. 2020;7:583897. Available from: http://www.ncbi.nlm.nih.gov/pubmed/33195334
  • Cotter A, Wallace D, McCarthy C, et al. The COVIRL002 Trial-Tocilizumab for management of severe, non-critical COVID-19 infection: a structured summary of a study protocol for a randomised controlled trial. Trials. 2020;21:20–22.
  • A study to evaluate the efficacy and safety of remdesivir plus tocilizumab compared with remdesivir plus placebo in hospitalized participants with severe COVID-19 pneumonia (REMDACTA) [Internet]. [cited 2021 Apr 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT04409262
  • Stone JH, Frigault MJ, Serling-Boyd NJ, et al. Efficacy of tocilizumab in patients hospitalized with Covid-19. N Engl J Med. 2020;383:2333–2344.
  • The RECOVERY Collaborative group. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;693–704.
  • Aziz MS, Cooper N, Douglas IS, et al. Tocilizumab in hospitalized patients with severe Covid-19 pneumonia. N Engl J Med 2021;384(16):1–14.
  • Hermine O, Mariette X, Tharaux PL, et al. Effect of tocilizumab vs usual care in adults hospitalized with COVID-19 and moderate or severe pneumonia: a randomized clinical trial. JAMA Intern Med. 2021;181:32–40.
  • Salvarani C, Dolci G, Massari M, et al. Effect of tocilizumab vs standard of care on clinical worsening in patients hospitalized with COVID-19 pneumonia: a randomized clinical trial. JAMA Intern Med. 2021;181:41–51.
  • Salama C, Han J, Yau L, et al. Tocilizumab in patients hospitalized with Covid-19 pneumonia. N Engl J Med. 2021;384:20–30.
  • Veiga VC, Prats JAGG, Farias DLC, et al. Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial. BMJ. 2021; 372:n84.
  • Investigators R-C. Interleukin-6 receptor antagonists in critically ill patients with Covid-19. N Engl J Med. 2021;384(16):1–12.
  • Horby PW, Campbell M, Staplin N, et al. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): preliminary results of a randomised, controlled, open-label, platform trial. medRxiv [Internet]. 2021;19. Available from: https://www.medrxiv.org/content/https://doi.org/10.1101/2021.02.11.21249258v1.
  • Campbell L, Chen C, Bhagat SS, et al. Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab: a systematic literature review and meta-analysis of randomized controlled trials. Rheumatology (Oxford). 2011;50:552–562.
  • Maeda T, Obata R, Rizk DOD, et al. The association of interleukin-6 value, interleukin inhibitors, and outcomes of patients with COVID-19 in New York City. J Med Virol. 2021;93:463–471.
  • Choy EH, De Benedetti F, Takeuchi T, et al. Translating IL-6 biology into effective treatments. Nat Rev Rheumatol. 2020;16:335–345.
  • Yamamoto K, Goto H, Hirao K, et al. Longterm safety of tocilizumab: results from 3 years of followup postmarketing surveillance of 5573 patients with rheumatoid arthritis in Japan. J Rheumatol. 2015;42:1368–1375.
  • Sepriano A, Kerschbaumer A, Smolen JS, et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2020;79(6):760-770.
  • Dodd LE, Freidlin B, Korn EL. Platform trials — beware the noncomparable control group. [Internet]. N Engl J Med. 2021;384;1572–1573. Available from: http://www.nejm.org/doi/https://doi.org/10.1056/NEJMc2102446
  • Mathew D, Giles JR, Baxter AE, et al. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science. 2020;1209:eabc8511.
  • Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area. JAMA [Internet]. 2020;323:2052. Available from: https://jamanetwork.com/journals/jama/fullarticle/2765184
  • Takahashi T, Ellingson MK, Wong P, et al. Sex differences in immune responses that underlie COVID-19 disease outcomes. Nature. 2020;588(7837)
  • Yang C, Liu M. Tocilizumab in treatment for patients with COVID-19. JAMA Intern Med. [ Internet]. 2021 Available from: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2778369
  • Bastida C, Ruiz-Esquide V, Pascal M, et al. Fixed dosing of intravenous tocilizumab in rheumatoid arthritis. Results from a population pharmacokinetic analysis. Br J Clin Pharmacol [Internet]. 2018;84:716–725. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29314183
  • Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus Remdesivir for hospitalized adults with Covid-19. N Engl J Med [Internet]. 2021;384:795–807.

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