IS TOCILIZUMAB AN EFFECTIVE THERAPY FOR SEVERE COVID-19: A SINGLE CENTER STUDY

Authors

  • Samreen Sarfaraz Infectious Disease Department, Indus Hospital and Health Network
  • Quratulain Shaikh Infectious Disease Department, Indus Hospital and Health Network
  • Sundus Iftikhar Maternal and Child Health, Interactive Research and Development, Pakistan
  • Fivzia Herekar Internal Medicine Department, Indus Hospital and Health Network
  • Syed Ghazanfar Saleem
  • Fatima Kanani Indus Hospital and Health Network

DOI:

https://doi.org/10.55519/JAMC-04-10963

Keywords:

COVID-19, Tocilizumab, mortality

Abstract

Background: The quest for effective therapies in Covid-19 continues. We compared the outcome of severe COVID-19 patients treated with and without Tocilizumab, an IL-6 inhibitor. Methods: This is a prospective cohort study on the clinical characteristics and outcomes of patients with Covid-19 patients admitted at The Indus Hospital and Health Network, Karachi between 24th March and 19th June 2020. Adult patients who received TCZ were compared with respect to mortality and days of hospitalization with those who did not. Results: A total of 88 patients including 41 patients in the TCZ group and 47 in non-TCZ group were recruited. Baseline demographic characteristics were comparable. TCZ group patients presented with worse clinical features including median SpO2 82% vs 88%, p<0.05 and CRP 193 vs 133.9 mg/L, p<0.05. Approximately, 85.4% were admitted in ICU compared to 69.8% in non-TCZ group, p>0.05. Mortality was not different among the groups (46% in TCZ group vs 51.1% in non-TCZ group, p>0.05). Median length of hospital stays, days of intubation, use of inotropic agents, and use of invasive ventilation or in-hospital complications were similar between the groups. Sub-group analysis revealed that mortality within TCZ group was associated with high IL-6 levels (173 vs 69.66 pg/ml, p<0.05), ICU admission (100% vs 72%, p<0.05), need for mechanical ventilation (100% vs 13.6%, p<0.05) and higher incidence of in-hospital complications, p<0.05. Conclusion: TCZ failed to demonstrate any mortality benefit in our patients. Non-survivors within the TCZ group were more critical compared to survivors and developed more in hospital complications.

References

WHO. WHO Director-General's opening remarks at the media briefing on COVID-19 - 11 March 2020. [Internet]. [cited 2022 May]. Available from: https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020

Worldometer. COVID-19 CORONAVIRUS PANDEMIC 2020. [Internet]. [cited 2022 May]. Available from: https://www.worldometers.info/coronavirus/

Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA 2020;323(11):1061–9.

Yang X, Yu Y, Xu J, Shu H, Liu H, Wu Y, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med 2020;8(5):475–81.

Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA 2020;323(20):2052–9.

Lau SK, Lau CC, Chan KH, Li CP, Chen H, Jin DY, et al. Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and treatment. J Gen Virol 2013;94(12):2679–90.

Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med 2020;180(7):934–43.

Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020;8(4):420–2.

Le RQ, Li L, Yuan W, Shord SS, Nie L, Habtemariam BA, et al. FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell‐induced severe or life‐threatening cytokine release syndrome. Oncologist 2018;23(8):943–7.

Wei PF. Diagnosis and treatment protocol for novel coronavirus pneumonia (Trial Version 7). Chin Med J (Engl) 2020;133(9):1087–95.

Toniati P, Piva S, Cattalini M, Garrafa E, Regola F, Castelli F, 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. Autoimmun Rev 2020;19(7):102568.

Fu B, Xu X, Wei H. Why tocilizumab could be an effective treatment for severe COVID-19? J Transl Med 2020;18(1):164.

Investigators R-C. Interleukin-6 receptor antagonists in critically ill patients with Covid-19. N Engl J Med 2021;384(16):1491–502.

Abani O, Abbas A, Abbas F, Abbas M, Abbasi S, Abbass H, et al. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2021;397(10285):1637–45.

Hermine O, Mariette X, Tharaux PL, Resche-Rigon M, Porcher R, Ravaud P, 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(1):32–40.

Salvarani C, Dolci G, Massari M, Merlo DF, Cavuto S, Savoldi L, et al. Effect of tocilizumab vs standard care on clinical worsening in patients hospitalized with COVID-19 pneumonia: a randomized clinical trial. JAMA Intern Med 2021;181(1):24–31.

Rosas IO, Bräu N, Waters M, Go RC, Hunter BD, Bhagani S, et al. Tocilizumab in hospitalized patients with severe Covid-19 pneumonia. N Engl J Med 2021;384(16):1503–16.

Hoffmann-La Roche A. Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients With Severe COVID-19 Pneumonia (COVACTA). NCT04320615. 2020.

Government of Pakistan Ministry of National Helath Service Regulations & Coordination. Clinical Management Guidelines for COVID-19 Infections 2020. [Internet]. [cited 2022 May]. Available from: http://covid.gov.pk/new_guidelines/04July2020_20200704_Clinical_Management_Guidelines_for_COVID-19_infections_1203.pdf

Sarfaraz S, Shaikh Q, Saleem SG, Rahim A, Herekar FF, Junejo S, et al. Determinants of in-hospital mortality in COVID-19; a prospective cohort study from Pakistan. PloS One 2021;16(5):e0251754.

WHO. Clinical management of COVID-19: interim guidance, 27 May 2020. World Health Organization; 2020.

Ghosn L, Chaimani A, Evrenoglou T, Davidson M, Graña C, Schmucker C, et al. Interleukin‐6 blocking agents for treating COVID‐19: a living systematic review. Cochrane Database Syst Rev 2021;3(3):CD013881.

NIH. COVID-19 Treatment Guidelines 2019. [Internet]. [cited 2022 May]. Available from: https://www.covid19treatmentguidelines.nih.gov/

IDSA. IDSA Guidelines on the Treatment and Management of Patients with COVID-19 2019. [Internet]. [cited 2022 May]. Available from: https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management

NHS. Interleukin-6 inhibitors (tocilizumab or sarilumab) for hospitalised patients with COVID-19 pneumonia (adults) 2019. [Internet]. [cited 2022 May]. Available from: https://www.cas.mhra.gov.uk/ViewandAcknowledgment/ViewAlert.aspx?AlertID=103144

Veiga VC, Prats JA, Farias DL, Rosa RG, Dourado LK, Zampieri FG, 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.

Capra R, De Rossi N, Mattioli F, Romanelli G, Scarpazza C, Sormani MP, et al. Impact of low dose tocilizumab on mortality rate in patients with COVID-19 related pneumonia. Eur J Intern Med 2020;76:31–5.

Campochiaro C, Della-Torre E, Cavalli G, De Luca G, Ripa M, Boffini N, et al. Efficacy and safety of tocilizumab in severe COVID-19 patients: a single-centre retrospective cohort study. Eur J Intern Med 2020;76:43–9.

Hariyanto TI, Hardyson W, Kurniawan A. Efficacy and safety of tocilizumab for coronavirus disease 2019 (Covid-19) patients: a systematic review and meta-analysis. Drug Res (Stuttg) 2021;71(5):265–74.

Knorr JP, Colomy V, Mauriello CM, Ha S. Tocilizumab in patients with severe COVID‐19: a single‐center observational analysis. J Med Virol 2020;92(11):2813–20.

Auld S, Caridi-Scheible M, Blum JM, Robichaux CJ, Kraft CS, Jacob JT, et al. ICU and ventilator mortality among critically ill adults with COVID-19. medRxiv 2020;2020:20076737.

Xu X, Han M, Li T, Sun W, Wang D, Fu B, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A. 2020;117(20):10970–5,10.1073/pnas.2005615117

Bester J, Pretorius E. Effects of IL-1β, IL-6 and IL-8 on erythrocytes, platelets and clot viscoelasticity. Sci Rep 2016;6(1):32188.

Coomes EA, Haghbayan H. Interleukin-6 in COVID-19: a systematic review and meta-analysis. Rev Med Virol 2020;30(6):1–9.

Alattar R, Ibrahim TB, Shaar SH, Abdalla S, Shukri K, Daghfal JN, et al. Tocilizumab for the Treatment of Severe COVID‐19. J Med Virol 2020;92(10):2042–9.

Published

2022-09-27

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