Efficacy of tocilizumab treatment in COVID-19 patients with cytokine release syndrome

Yıl 2021, , 269 - 275, 01.03.2021

Betül Erişmiş , Hakan Koçoğlu , Fatma Ekşi Zuhal Yeşilbağ , Esra Canbolat Ünlü , Faruk Karandere Melek Yalçın Mutlu Ozan Cemal Icacan Semsi Karabela , Mehmet Hurşitoğlu , Nilgün Işıksaçan , Hayat Kumbasar

https://doi.org/10.28982/josam.876637

Öz

Background/Aim: Cytokine release syndrome, a potentially life-threatening condition in SARS‐CoV‐2 (COVID-19) patients, plays a critical role that may lead to the prioritization of tocilizumab (TCZ) in the treatment of this disease. We aimed to present our TCZ-treated SARS‐CoV‐2 patients’ data that might help and guide clinicians in dealing with this infectious disease in their daily practice and research.
Methods: This is a retrospective multicenter cohort study from two Turkish pandemic centers. A total of 5165 patients’ data who were hospitalized due to SARS‐CoV‐2 pneumonia from March 16 to May 20, 2020 were screened and 72 patients treated with TCZ were included in the study. We evaluated patients' demographic data, laboratory and imaging studies, and clinical outcomes and the effect of TCZ treatment on patients' laboratory and clinical results.
Results: O2 saturation levels significantly increased, and fever significantly decreased on the 5th day after TCZ therapy compared to before its initiation (P=0.001, P=0.010, respectively). The decrease in troponin-I, creatinine, LDH, fibrinogen, CRP, procalcitonin, CK, and ferritin levels after TCZ therapy were significant (P<0.05 for all). There was no significant difference in mortality rates with regards to CT results, duration of hospitalization, and the location of initiation of TCZ therapy (clinic vs. ICU) (P>0.05 for all). Importantly, we found a significant increase in mortality rates in patients who received azithromycin, oseltamivir, and ascorbic acid treatments compared to those who did not receive those treatments (P<0.05 for all).
Conclusion: Our results showed that TCZ treatment may improve the SpO2 levels, fever and laboratory findings and repress further deterioration of severe SARS-CoV-2 patients. TCZ treatment can be given to the patients in non-ICU clinical beds. It is obvious that randomized controlled studies are needed to observe the efficacy of tocilizumab treatment in COVID-19 patients more clearly.

Anahtar Kelimeler

COVID-19, tocilizumab, SARS-CoV-2, cytokine release syndrome

Destekleyen Kurum

None

Kaynakça

• 1. World Health Organisation. Coronavirus disease (COVID-2019) situation reports. Weekly Epidemiological Update — 12 October 2020. Retrieved from: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20201012-weekly-epi-update-9.pdf
• 2. 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 Jul 1;180(7):934-943. doi: 10.1001/jamainternmed.2020.0994. Erratum in: JAMA Intern Med. 2020 Jul 1;180(7):1031. PMID: 32167524; PMCID: PMC7070509.
• 3. Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020 Jul 28;71(15):762-768. doi: 10.1093/cid/ciaa248. PMID: 32161940; PMCID: PMC7108125.
• 4. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30. PMID: 32007143; PMCID: PMC7135076.
• 5. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum in: Lancet. 2020 Jan 30;: PMID: 31986264; PMCID: PMC7159299.
• 6. 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 Apr;8(4):420-422. doi: 10.1016/S2213-2600(20)30076-X. Epub 2020 Feb 18. Erratum in: Lancet Respir Med. 2020 Feb 25; PMID: 32085846; PMCID: PMC7164771.
• 7. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017 Jul;39(5):529-539. doi: 10.1007/s00281-017-0629-x. Epub 2017 May 2. PMID: 28466096; PMCID: PMC7079893.
• 8. Li G, Fan Y, Lai Y, Han T, Li Z, Zhou P, et al. Coronavirus infections and immune responses. J Med Virol. 2020 Apr;92(4):424-432. doi: 10.1002/jmv.25685. Epub 2020 Feb 7. PMID: 31981224; PMCID: PMC7166547.
• 9. McGonagle D, Sharif K, O'Regan A, Bridgewood C. The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease. Autoimmun Rev. 2020 Jun;19(6):102537. doi: 10.1016/j.autrev.2020.102537. Epub 2020 Apr 3. PMID: 32251717; PMCID: PMC7195002.
• 10. Wan S, Yi Q, Fan S, Lv J, Zhang X, Guo L, et al. Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP). medRxiv 2020.02.10.20021832; doi: 10.1101/2020.02.10.20021832
• 11. Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 May;46(5):846-848. doi: 10.1007/s00134-020-05991-x. Epub 2020 Mar 3. Erratum in: Intensive Care Med. 2020 Apr 6;: PMID: 32125452; PMCID: PMC7080116.
• 12. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16. PMID: 32192578; PMCID: PMC7270045.
• 13. Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents. 2020 May;55(5):105954. doi: 10.1016/j.ijantimicag.2020.105954. Epub 2020 Mar 29. PMID: 32234467; PMCID: PMC7118634.
• 14. Luo P, Liu Y, Qiu L, Liu X, Liu D, Li J. Tocilizumab treatment in COVID-19: A single center experience. J Med Virol. 2020 Jul;92(7):814-818. doi: 10.1002/jmv.25801. Epub 2020 Apr 15. PMID: 32253759; PMCID: PMC7262125.
• 15. Kaly L, Rosner I. Tocilizumab - a novel therapy for non-organ-specific autoimmune diseases. Best Pract Res Clin Rheumatol. 2012 Feb;26(1):157-65. doi: 10.1016/j.berh.2012.01.001. PMID: 22424201.
• 16. 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 Aug;23(8):943-947. doi: 10.1634/theoncologist.2018-0028. Epub 2018 Apr 5. PMID: 29622697; PMCID: PMC6156173.
• 17. Scott LJ. Tocilizumab: A Review in Rheumatoid Arthritis. Drugs. 2017 Nov;77(17):1865-1879. doi: 10.1007/s40265-017-0829-7. Erratum in: Drugs. 2017 Dec 19; PMID: 29094311; PMCID: PMC5736769.
• 18. Yokota S, Imagawa T, Mori M, Miyamae T, Aihara Y, Takei S, et al. Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. Lancet. 2008 Mar 22;371(9617):998-1006. doi: 10.1016/S0140-6736(08)60454-7. PMID: 18358927. .
• 19. Gabay C, Emery P, van Vollenhoven R, Dikranian A, Alten R, Pavelka K, et al; ADACTA Study Investigators. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet. 2013 May 4;381(9877):1541-50. doi: 10.1016/S0140-6736(13)60250-0. Epub 2013 Mar 18. Erratum in: Lancet. 2013 Dec 7;382(9908):1878. Erratum in: Lancet. 2013 May 4;381(9877):1540. Dosage error in article text. PMID: 23515142.
• 20. Cortegiani A, Ippolito M, Greco M, Granone V, Protti A, Gregoretti C, et al. Rationale and evidence on the use of tocilizumab in COVID-19: a systematic review. Pulmonology. 2021 Jan-Feb;27(1):52-66. doi: 10.1016/j.pulmoe.2020.07.003. Epub 2020 Jul 20. PMID: 32713784; PMCID: PMC7369580.
• 21. Republic of Turkey Ministry of Health. Covid-19 (SARS-CoV-2 Infection) Guide - Science Board Study. Available at: https://covid19bilgi.saglik.gov.tr/depo/rehberler/COVID-19_Rehberi.pdf?type=file (Accessed 05/07/2020)
• 22. Yang R, Li X, Liu H, Zhen Y, Zhang X, Xiong Q, et al. Chest CT Severity Score: An Imaging Tool for Assessing Severe COVID-19. Radiol Cardiothorac Imaging. 2020 Mar 30;2(2):e200047. doi: 10.1148/ryct.2020200047. PMCID: PMC7233443.
• 23. Aomar-Millán IF, Salvatierra J, Torres-Parejo Ú, Faro-Miguez N, Callejas-Rubio JL, Ceballos-Torres Á. Anakinra after treatment with corticosteroids alone or with tocilizumab in patients with severe COVID-19 pneumonia and moderate hyperinflammation. A retrospective cohort study. Intern Emerg Med. 2021 Jan 5:1–10. doi: 10.1007/s11739-020-02600-z. Epub ahead of print. PMID: 33400157; PMCID: PMC7782569.
• 24. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, 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 May;8(5):475-481. doi: 10.1016/S2213-2600(20)30079-5. Epub 2020 Feb 24. Erratum in: Lancet Respir Med. 2020 Apr;8(4):e26. PMID: 32105632; PMCID: PMC7102538.
• 25. Arentz M, Yim E, Klaff L, Lokhandwala S, Riedo FX, Chong M, et al. Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State. JAMA. 2020 Apr 28;323(16):1612-1614. doi: 10.1001/jama.2020.4326. PMID: 32191259; PMCID: PMC7082763.
• 26. 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 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585. PMID: 32031570; PMCID: PMC7042881.
• 27. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. PMID: 32091533.
• 28. Zhou F, Yu T, Du R, Fan G, Liu Z,Xiang J, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11. Erratum in: Lancet. 2020 Mar 28;395(10229):1038. PMID: 32171076; PMCID: PMC7270627.
• 29. Bhatraju PK, Ghassemieh BJ, Nichols M, Kim R, Jerome KR, Nalla AK, et al. Covid-19 in Critically Ill Patients in the Seattle Region - Case Series. N Engl J Med. 2020 May 21;382(21):2012-2022. doi: 10.1056/NEJMoa2004500. Epub 2020 Mar 30. PMID: 32227758; PMCID: PMC7143164.
• 30. ICNARC report on COVID-19 in critical care. London: Intensive Care National Audit & Research Centre, March 27, 2020 (https://www.icnarc.org/DataServices /Attachments/Download/b5f59585-5870 -ea11-9124-00505601089b)
• 31. Shekhar R, Sheikh AB, Upadhyay S, Atencio J, Kapuria D. Early experience with COVID-19 patients at academic hospital in Southwestern United States. Infect Dis (Lond). 2020 Aug;52(8):596-599. doi: 10.1080/23744235.2020.1774645. Epub 2020 Jun 1. PMID: 32476537.
• 32. Media & Investor Release. Roche provides an update on the phase III COVACTA trial of Actemra/RoActemra in hospitalised patients with severe COVID-19 associated pneumonia. Retrieved from: https://www.roche.com/investors/updates/inv-update-2020-07-29.htm (accessed at: October 11, 2020)
• 33. Media & Investor Release. Roche’s phase III EMPACTA study showed Actemra/RoActemra reduced the likelihood of needing mechanical ventilation in hospitalised patients with COVID-19 associated pneumonia. Retrieved from: https://www.roche.com/media/releases/med-cor-2020-09-18.htm (accessed at: October 11, 2020)
• 34. Media & Investor Release. Roche initiates phase III clinical trial of Actemra/RoActemra plus remdesivir in hospitalised patients with severe COVID-19 pneumonia. Retrieved from: https://www.roche.com/media/releases/med-cor-2020-05-28.htm (accessed at: October 11, 2020)