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Evaluation of Treatment with a single (400mg) versus double dose (800mg) of Tocilizumab in Acute Respiratory Distress Syndrome Associated with COVID-19Pneumonia

Yıl 2022, Cilt 12, Sayı 1, 134 - 138, 15.01.2022
https://doi.org/10.16899/jcm.1031086

Öz

Background: COVID-19 is a viral infectious caused by novel coronavirus called as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent studies have shown that the level of IL-6 in the severe infection group was higher than that in the moderate group, suggesting that IL-6 can be used as a biomarker for severity assessment. However, the correlation of IL-6 levels in critically ill patients is still unknown. Tocilizumab is a monoclonal antibody against the IL-6 receptor and commonly used for cytokine storm or macrophage activation syndrome (MAS) in COVID-19 patients. Objective: In this study, we wanted to compare the clinical outcomes of different doses of tocilizumab (400 mg and 800 mg) as treatment. Methods:In this retrospective analysis we have included 120 patients with mild Acute Respiratory Distress Syndrome (ARDS) associated with COVID-19 pneumonia who received tocilizumab 400 mg once or twice daily. The two treatment groups were compared in terms of age, gender, comorbid diseases, arterial oxygen pressure (PaO2), oxygen saturation (SaO2) on room air, admission to the intensive care, length of stay in the intensive care unit, status of intubation, mortality, C reactive protein, white blood cell count, platelets, neutrophil, lymphocyte, ferritin, D-dimer, procalcitonin levels. Results: There were no statistically significant difference between the two dosing regimens in gender, arterial oxygen pressure (PaO2), oxygen saturation (SaO2) on room air, comorbidities, need for intubation, mortality, requirement for intensive care, total length of hospital stay, length of stay in intensive care, CRP, WBC, platelets, neutrophils, lymphocytes, ferritin, D-dimer and procalcitonin levels. Conclusion : Currently the short and long term adverse effects of tocilizumab have not been clearly reported in the literature. The clinical outcomes of once or twice daily tocilizumab did not differ significantly in terms of efficacy. Therefore a single dose of 400 mg once daily tocilizumab could be a rational treatment option.

Kaynakça

  • 1. Li Q, Guan X, Wu P et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020 Mar 26;382(13):1199-120. doi: 10.1056/NEJMoa2001316. Epub 2020 Jan 29. PMID: 31995857; PMCID: PMC7121484.
  • 2. Wu C, Chen X, Cai Y 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. Santosha A Vardhana, Jedd D Wolchok. The many faces of the anti-COVID immune response. J Exp Med. 2020 Jun 1;217(6): e20200678. doi: 10.1084/jem.20200678. PMID: 32353870; PMCID: PMC7191310.
  • 4. L Chen, H G Liu, W Liu et al. Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia. Zhonghua Jie He He Hu Xi Za Zhi. 2020 Mar 12;43(3):203-208.
  • 5. Zumla A, Hui DS, Azhar EI, Memish ZA, Maeurer M. Reducing mortality from 2019-nCoV: host-directed therapies should be an option. Lancet. 2020 Feb 22;395(10224): e35-e36.
  • 6. Chen L, Liu HG, Liu W, Liu J, Liu K, Shang J, Deng Y, Wei S. [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia]. Zhonghua Jie He He Hu Xi Za Zhi. 2020 Mar 12;43(3):203-208. Chinese. doi: 10.3760/cma.j.issn.1001-0939.2020.03.013. PMID: 32164089.
  • 7. Fan Wang, Jiayan Nie, Haizhou Wang et al. Characteristics of Peripheral Lymphocyte Subset Alteration in COVID-19 Pneumonia. J Infect Dis. 2020 May 11;221(11):1762-1769.https://doi.org/10.1101/2020.02.10.20021832.
  • 8. Nicola Potere, Marcello Di Nisio, Donatella Cibelli, et al. Interleukin-6 receptor blockade with subcutaneous tocilizumab in severe COVID-19 pneumonia and hyperinflammation: a case-control study. Ann Rheum Dis. 2021 Feb;80(2):1-2.doi:10.1136/ annrheumdis-2020-218243.
  • 9. Xiaoling Xu, Mingfeng Han, Tiantian Li et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci USA. 2020 May 19;117(20):10970-10975. doi: 10.1073/pnas.2005615117. Epub 2020 Apr 29. PMID: 32350134; PMCID: PMC7245089.
  • 10. Konstantinos F, Anastasia B, Raymond N. Systematic review of the prevalence of current smoking among hospitalized COVID-19 patients in China: Could nicotine be a therapeutic option?". Intern Emerg Med. 2020 Aug;15(5):845-852. doi: 10.1007/s11739-020-02355-7. Epub 2020 May 9.
  • 11. Jonathan P Wong, Satya Viswanathan, Ming Wang, et al. "Current and future developments in the treatment of virus-induced hypercytokinemia". Future Med Chem. 2017 Feb;9(2):169-178.doi:10.4155/fmc- 2016-0181. ISSN 1756-8927. PMC 7079716. PMID 28128003.
  • 12. Qiang Liu, Yuan-hong Zhou, Zhan-qiu Yang "The cytokine storm of severe influenza and development of immunomodulatory therapy". Cell Mol Immunol. 2016 Jan;13(1):3-10. doi:10.1038/cmi.2015.74. PMC 4711683. PMID 26189369.
  • 13. Sonu Bhaskar, Akansha Sinha, Maciej Banach, et al. The cytokine storm of severe influenza and development of immunomodulatory therapy. Cell Mol Immunol. 2016 Jan;13(1):3-10.doi: 10.3389/fimmu.2020.01648.
  • 14. Danielle Byrne, Siobhan B O' Neill, Nestor L Müller, et al. RSNA Expert Consensus Statement on Reporting Chest CT Findings Related to COVID-19: Interobserver Agreement Between Chest Radiologists. Can Assoc Radiol J. 2021 Feb;72(1):159-166.doi: 10.1177/0846537120938328. Epub 2020 Jul 2. PMID: 32615802; PMCID: PMC7335944.
  • 15. Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr;8(4):420-422.
  • 16. Eimer J, Vesterbacka J, Svensson AK, Stojanovic B, Wagrell C, Sönnerborg A, Nowak P. Tocilizumab shortens time on mechanical ventilation and length of hospital stay in patients with severe COVID-19: a retrospective cohort study. J Intern Med. 2021 Mar;289(3):434-436. doi: 10.1016/S2213-2600(20)30076-X. Epub 2020 Feb 18. Erratum in: Lancet Respir Med. 2020 Feb 25: PMID: 32085846; PMCID: PMC7164771.
  • 17. Jishnu Malgie, Jan W Schoones, Bart G Pijls. Decreased Mortality in Coronavirus Disease 2019 Patients Treated with Tocilizumab: A Rapid Systematic Review and Meta-analysis of Observational Studies. Clin Infect Dis. 2021 Jun 1;72(11):e742-e749. doi: 10.1093/cid/ciaa1445. PMID: 32964913; PMCID: PMC7543350.
  • 18. 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. Autoimmun Rev. 2020 Jul;19(7):102568. doi: 10.1016/j.autrev.2020.102568. Epub 2020 May 3. PMID: 32376398; PMCID: PMC7252115.
  • 19. Colaneri M, Bogliolo L, Valsecchi P, et al. Tocilizumab for Treatment of Severe COVID-19 Patients: Preliminary Results from SMAtteo COvid19 REgistry (SMACORE). Microorganisms. 2020 May 9;8(5):695. doi: 10.3390/microorganisms8050695. PMID: 32397399; PMCID: PMC7285503.
  • 20. Alattar R, Ibrahim TBH, Shaar SH, et al. Tocilizumab for the treatment of severe coronavirus disease 2019. J Med Virol. 2020 Oct;92(10):2042-2049. doi: 10.1002/jmv.25964. Epub 2020 May 10. PMID: 32369191; PMCID: PMC7267594.
  • 21. 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.
  • 22. Dastan F, Saffaei A, Haseli S, et al. Promising effects of tocilizumab in COVID-19: A non-controlled, prospective clinical trial. Int Immunopharmacol. 2020 Nov;88:106869.doi: 10.1016/j.intimp.2020.106869. Epub 2020 Aug 4. PMID: 32889241; PMCID: PMC7402206.
  • 23. Carlo Salvarani, Giovanni Dolci, Marco Massari, 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. doi:10.1001/jamainternmed.2020.6615.
  • 24. A Cortegiani, M Ippolito, M Greco, et al. Rationale and evidence on the use of tocilizumab in COVID-19: a systematic review. Pulmonology. Jan-Feb 2021;27(1):52-66.doi:10.1016/j.pulmoe2020.07.003.
  • 25. Baek HJ, Lim MJ, Park W, et al. Efficacy and safety of tocilizumab in Korean patients with active rheumatoid arthritis. Korean J Intern Med. 2019 Jul;34(4):917-931.doi: 10.3904/kjim.2017.159. Epub 2018 Jan 17. PMID: 29334721; PMCID: PMC6610180.

COVID-19 Pnömonisi ile İlişkili Akut Solunum Sıkıntısı Sendromunda tek doz (400 mg) ve çift doz (800 mg) Tocilizumab ile Tedavinin Değerlendirilmesi

Yıl 2022, Cilt 12, Sayı 1, 134 - 138, 15.01.2022
https://doi.org/10.16899/jcm.1031086

Öz

Arka plan: COVID-19, şiddetli akut solunum sendromu koronavirüs 2 (SARS-CoV-2) olarak adlandırılan yeni koronavirüsün neden olduğu viral bir enfeksiyondur. Son çalışmalar, şiddetli enfeksiyon grubundaki IL-6 seviyesinin orta gruptan daha yüksek olduğunu göstermiştir, bu da IL-6'nın şiddet değerlendirmesi için bir biyobelirteç olarak kullanılabileceğini düşündürmektedir. Bununla birlikte, kritik hastalardaki IL-6 düzeylerinin korelasyonu hala bilinmemektedir. Tocilizumab, IL-6 reseptörüne karşı monoklonal bir antikordur ve COVID-19 hastalarında sitokin fırtınası veya makrofaj aktivasyon sendromu (MAS) için yaygın olarak kullanılır. Amaç: Bu çalışmada, tedavi olarak farklı dozlarda tocilizumabın (400 mg ve 800 mg) klinik sonuçlarını karşılaştırmak istedik. Yöntemler: Bu retrospektif analize, günde bir veya iki kez 400 mg tocilizumab alan COVID-19 pnömonisi ile ilişkili hafif Akut Solunum Sıkıntısı Sendromu (ARDS) olan 120 hastayı dahil ettik. İki tedavi grubu yaş, cinsiyet, eşlik eden hastalıklar, arteriyel oksijen basıncı (PaO2), oda havasında oksijen satürasyonu (SaO2), yoğun bakıma yatış, yoğun bakımda kalış süresi, entübasyon durumu açısından karşılaştırıldı. , mortalite, C reaktif protein, beyaz kan hücresi sayısı, trombositler, nötrofil, lenfosit, ferritin, D-dimer, prokalsitonin seviyeleri. Bulgular: Cinsiyet, arteriyel oksijen basıncı (PaO2), oda havasında oksijen satürasyonu (SaO2), komorbiditeler, entübasyon ihtiyacı, mortalite, yoğun bakım gereksinimi, toplam hastanede kalış süresi açısından iki doz rejimi arasında istatistiksel olarak anlamlı bir fark yoktu. , yoğun bakımda kalış süresi, CRP, WBC, trombosit, nötrofil, lenfosit, ferritin, D-dimer ve prokalsitonin düzeyleri. Sonuç : Halihazırda tocilizumabın kısa ve uzun dönem yan etkileri literatürde net olarak bildirilmemiştir. Günde bir veya iki kez tocilizumabın klinik sonuçları, etkinlik açısından önemli ölçüde farklılık göstermedi. Bu nedenle günde bir kez 400 mg'lık tek doz tocilizumab rasyonel bir tedavi seçeneği olabilir.

Kaynakça

  • 1. Li Q, Guan X, Wu P et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020 Mar 26;382(13):1199-120. doi: 10.1056/NEJMoa2001316. Epub 2020 Jan 29. PMID: 31995857; PMCID: PMC7121484.
  • 2. Wu C, Chen X, Cai Y 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. Santosha A Vardhana, Jedd D Wolchok. The many faces of the anti-COVID immune response. J Exp Med. 2020 Jun 1;217(6): e20200678. doi: 10.1084/jem.20200678. PMID: 32353870; PMCID: PMC7191310.
  • 4. L Chen, H G Liu, W Liu et al. Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia. Zhonghua Jie He He Hu Xi Za Zhi. 2020 Mar 12;43(3):203-208.
  • 5. Zumla A, Hui DS, Azhar EI, Memish ZA, Maeurer M. Reducing mortality from 2019-nCoV: host-directed therapies should be an option. Lancet. 2020 Feb 22;395(10224): e35-e36.
  • 6. Chen L, Liu HG, Liu W, Liu J, Liu K, Shang J, Deng Y, Wei S. [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia]. Zhonghua Jie He He Hu Xi Za Zhi. 2020 Mar 12;43(3):203-208. Chinese. doi: 10.3760/cma.j.issn.1001-0939.2020.03.013. PMID: 32164089.
  • 7. Fan Wang, Jiayan Nie, Haizhou Wang et al. Characteristics of Peripheral Lymphocyte Subset Alteration in COVID-19 Pneumonia. J Infect Dis. 2020 May 11;221(11):1762-1769.https://doi.org/10.1101/2020.02.10.20021832.
  • 8. Nicola Potere, Marcello Di Nisio, Donatella Cibelli, et al. Interleukin-6 receptor blockade with subcutaneous tocilizumab in severe COVID-19 pneumonia and hyperinflammation: a case-control study. Ann Rheum Dis. 2021 Feb;80(2):1-2.doi:10.1136/ annrheumdis-2020-218243.
  • 9. Xiaoling Xu, Mingfeng Han, Tiantian Li et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci USA. 2020 May 19;117(20):10970-10975. doi: 10.1073/pnas.2005615117. Epub 2020 Apr 29. PMID: 32350134; PMCID: PMC7245089.
  • 10. Konstantinos F, Anastasia B, Raymond N. Systematic review of the prevalence of current smoking among hospitalized COVID-19 patients in China: Could nicotine be a therapeutic option?". Intern Emerg Med. 2020 Aug;15(5):845-852. doi: 10.1007/s11739-020-02355-7. Epub 2020 May 9.
  • 11. Jonathan P Wong, Satya Viswanathan, Ming Wang, et al. "Current and future developments in the treatment of virus-induced hypercytokinemia". Future Med Chem. 2017 Feb;9(2):169-178.doi:10.4155/fmc- 2016-0181. ISSN 1756-8927. PMC 7079716. PMID 28128003.
  • 12. Qiang Liu, Yuan-hong Zhou, Zhan-qiu Yang "The cytokine storm of severe influenza and development of immunomodulatory therapy". Cell Mol Immunol. 2016 Jan;13(1):3-10. doi:10.1038/cmi.2015.74. PMC 4711683. PMID 26189369.
  • 13. Sonu Bhaskar, Akansha Sinha, Maciej Banach, et al. The cytokine storm of severe influenza and development of immunomodulatory therapy. Cell Mol Immunol. 2016 Jan;13(1):3-10.doi: 10.3389/fimmu.2020.01648.
  • 14. Danielle Byrne, Siobhan B O' Neill, Nestor L Müller, et al. RSNA Expert Consensus Statement on Reporting Chest CT Findings Related to COVID-19: Interobserver Agreement Between Chest Radiologists. Can Assoc Radiol J. 2021 Feb;72(1):159-166.doi: 10.1177/0846537120938328. Epub 2020 Jul 2. PMID: 32615802; PMCID: PMC7335944.
  • 15. Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr;8(4):420-422.
  • 16. Eimer J, Vesterbacka J, Svensson AK, Stojanovic B, Wagrell C, Sönnerborg A, Nowak P. Tocilizumab shortens time on mechanical ventilation and length of hospital stay in patients with severe COVID-19: a retrospective cohort study. J Intern Med. 2021 Mar;289(3):434-436. doi: 10.1016/S2213-2600(20)30076-X. Epub 2020 Feb 18. Erratum in: Lancet Respir Med. 2020 Feb 25: PMID: 32085846; PMCID: PMC7164771.
  • 17. Jishnu Malgie, Jan W Schoones, Bart G Pijls. Decreased Mortality in Coronavirus Disease 2019 Patients Treated with Tocilizumab: A Rapid Systematic Review and Meta-analysis of Observational Studies. Clin Infect Dis. 2021 Jun 1;72(11):e742-e749. doi: 10.1093/cid/ciaa1445. PMID: 32964913; PMCID: PMC7543350.
  • 18. 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. Autoimmun Rev. 2020 Jul;19(7):102568. doi: 10.1016/j.autrev.2020.102568. Epub 2020 May 3. PMID: 32376398; PMCID: PMC7252115.
  • 19. Colaneri M, Bogliolo L, Valsecchi P, et al. Tocilizumab for Treatment of Severe COVID-19 Patients: Preliminary Results from SMAtteo COvid19 REgistry (SMACORE). Microorganisms. 2020 May 9;8(5):695. doi: 10.3390/microorganisms8050695. PMID: 32397399; PMCID: PMC7285503.
  • 20. Alattar R, Ibrahim TBH, Shaar SH, et al. Tocilizumab for the treatment of severe coronavirus disease 2019. J Med Virol. 2020 Oct;92(10):2042-2049. doi: 10.1002/jmv.25964. Epub 2020 May 10. PMID: 32369191; PMCID: PMC7267594.
  • 21. 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.
  • 22. Dastan F, Saffaei A, Haseli S, et al. Promising effects of tocilizumab in COVID-19: A non-controlled, prospective clinical trial. Int Immunopharmacol. 2020 Nov;88:106869.doi: 10.1016/j.intimp.2020.106869. Epub 2020 Aug 4. PMID: 32889241; PMCID: PMC7402206.
  • 23. Carlo Salvarani, Giovanni Dolci, Marco Massari, 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. doi:10.1001/jamainternmed.2020.6615.
  • 24. A Cortegiani, M Ippolito, M Greco, et al. Rationale and evidence on the use of tocilizumab in COVID-19: a systematic review. Pulmonology. Jan-Feb 2021;27(1):52-66.doi:10.1016/j.pulmoe2020.07.003.
  • 25. Baek HJ, Lim MJ, Park W, et al. Efficacy and safety of tocilizumab in Korean patients with active rheumatoid arthritis. Korean J Intern Med. 2019 Jul;34(4):917-931.doi: 10.3904/kjim.2017.159. Epub 2018 Jan 17. PMID: 29334721; PMCID: PMC6610180.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Bilimleri ve Hizmetleri
Bölüm Orjinal Araştırma
Yazarlar

Barış ÇİL (Sorumlu Yazar)
0000-0003-1090-0697
Türkiye


Mehmet KABAK
0000-0003-4781-1751
Türkiye

Destekleyen Kurum YOK
Proje Numarası YOK
Yayımlanma Tarihi 15 Ocak 2022
Kabul Tarihi 18 Aralık 2021
Yayınlandığı Sayı Yıl 2022, Cilt 12, Sayı 1

Kaynak Göster

AMA Çil B. , Kabak M. Evaluation of Treatment with a single (400mg) versus double dose (800mg) of Tocilizumab in Acute Respiratory Distress Syndrome Associated with COVID-19Pneumonia. J Contemp Med. 2022; 12(1): 134-138.