Use of the rheumatic drug tocilizumab for treatment of SARS-CoV-2 patients
1
Department of Rheumatology, Rehabilitation and Internal Medicine, Poznan University of Medical Sciences, Poland
Online publication date: 2021-09-08
Reumatologia 2021;(Konferencja Pacjent post-COVID-owy. Co zostaje, a co się zmienia? 1):252-259
KEYWORDS
ABSTRACT
Coronavirus disease 2019 (COVID-19) is a highly infectious respiratory disease caused by a new coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has been observed to vary in its degree of symptoms. One of the most important clinical manifestations is pneumonia and the subsequent worsening of the hyperinflammatory state and cytokine storm.
Tocilizumab (TCB) is a recombinant humanized, anti-human monoclonal antibody of the immunoglobulin G1k (IgG1k) subclass that acts against soluble and membrane-bound interleukin six receptors (IL-6R). There is wide use of TCB in rheumatic diseases. However, recently this medication has been used in the treatment of SARS-CoV-2 infection. Tocilizumab application in COVID-19 patients with a high risk of a cytokine storm shows a positive response in reducing the mortality rate. Moreover, TCB minimizes the time needed to recover, improves oxygenation, shortens the duration of vasopressor support, and reduces the likelihood of invasive mechanical ventilation.
Therefore we provide an overview of recent studies to understand the efficacy of this drug under various circumstances, including COVID-19 and rheumatic pathologies. This article also explores and integrates the different treatment possibilities in prominent anti-inflammatory and immune-modulatory-related symptoms. The preliminary data demonstrate promising results regarding the efficacy of TCB use in severe COVID-19 patients. Nevertheless, randomized controlled trials, with adequate sample sizes and sufficient follow-up periods, are needed to form conclusions and establish treatment recommendations.
Tocilizumab (TCB) is a recombinant humanized, anti-human monoclonal antibody of the immunoglobulin G1k (IgG1k) subclass that acts against soluble and membrane-bound interleukin six receptors (IL-6R). There is wide use of TCB in rheumatic diseases. However, recently this medication has been used in the treatment of SARS-CoV-2 infection. Tocilizumab application in COVID-19 patients with a high risk of a cytokine storm shows a positive response in reducing the mortality rate. Moreover, TCB minimizes the time needed to recover, improves oxygenation, shortens the duration of vasopressor support, and reduces the likelihood of invasive mechanical ventilation.
Therefore we provide an overview of recent studies to understand the efficacy of this drug under various circumstances, including COVID-19 and rheumatic pathologies. This article also explores and integrates the different treatment possibilities in prominent anti-inflammatory and immune-modulatory-related symptoms. The preliminary data demonstrate promising results regarding the efficacy of TCB use in severe COVID-19 patients. Nevertheless, randomized controlled trials, with adequate sample sizes and sufficient follow-up periods, are needed to form conclusions and establish treatment recommendations.
REFERENCES (64)
1.
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497–506, DOI: 10.1016/S0140-6736(20)30183-5.
2.
Baloch S, Baloch MA, Zheng T, Pei X. The coronavirus disease 2019 (COVID-19) pandemic. Tohoku J Exp Med 2020; 250: 271–278, DOI: 10.1620/tjem.250.271.
3.
Asselah T, Durantel D, Pasmant E, et al. COVID-19: Discovery, diagnostics and drug development. J Hepatol 2021; 74: 168–184, DOI: 10.1016/j.jhep.2020.09.031.
4.
Lotfi M, Hamblin MR, Rezaei N. COVID-19: transmission, prevention, and potential therapeutic opportunities. Clin Chim Acta 2020; 508: 254–266, DOI: 10.1016/j.cca.2020.05.044.
5.
Ragab D, Salah Eldin H, Taeimah M, et al. The COVID-19 cytokine storm; what we know so far. Front Immunol 2020 16; 11: 1446, DOI: 10.3389/fimmu.2020.01446.
6.
Wiersinga WJ, Rhodes A, Cheng AC, et al. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19). JAMA 2020; 324: 782, DOI: 10.1001/jama.2020.12839.
7.
Cascella M, Rajnik M, Aleem A, et al. Features, evaluation, and treatment of coronavirus (COVID-19) [Updated 2021]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 [Available from: https://www.ncbi.nlm.nih.gov/b...].
8.
Amraei R, Rahimi N. COVID-19, renin–angiotensin system and endothelial dysfunction. Cells 2020; 9: 1652, DOI: 10.3390/cells9071652.
9.
Hu B, Huang S, Yin L. The cytokine storm and COVID-19. J Med Virol 2021; 93: 250–256, DOI: 10.1002/jmv.26232.
10.
Scott LJ. Tocilizumab: a review in rheumatoid arthritis. Drugs 2017; 77: 1865–1879, DOI: 10.1007/s40265-017-0829-7.
11.
Samaee H, Mohsenzadegan M, Ala S, et al. Tocilizumab for treatment patients with COVID-19: recommended medication for novel disease. Int Immunopharmacol 2020; 89: 107018, DOI: 10.1016/j.intimp.2020.107018.
12.
Tanaka T, Narazaki M, Kishimoto T. Interleukin (IL-6) immunotherapy. Cold Spring Harb Perspect Biol 2018; 10: a028456, DOI: 10.1101/cshperspect.a028456.
13.
Luo P, Liu Y, Qiu L, et al. Tocilizumab treatment in COVID-19: a single center experience. J Med Virol 2020; 92: 814–818, DOI: 10.1002/jmv.25801.
14.
Li Q, Guan X, Wu P, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med 2020; 382: 1199–1207, DOI: 10.1056/NEJMoa2001316.
15.
Sheppard M, Laskou F, Stapleton PP, et al. Tocilizumab (Actemra). Hum Vaccin Immunother 2017; 13: 1972–1988, DOI: 10.1080/21645515.2017.1316909.
16.
Fajgenbaum DC, June CH. Cytokine Storm. Longo DL, editor. N Engl J Med 2020; 383: 2255–2273, DOI: 10.1056/NEJMra2026131.
17.
Nile SH, Nile A, Qiu J, et al. COVID-19: pathogenesis, cytokine storm and therapeutic potential of interferons. Cytokine Growth Factor Rev 2020; 53: 66–70, DOI: 10.1016/j.cytogfr.2020.05.002.
18.
Caricchio R, Gallucci M, Dass C, et al. Preliminary predictive criteria for COVID-19 cytokine storm. Ann Rheum Dis 2020; 80: 88–95, DOI: 10.1136/annrheumdis-2020-218323.
19.
Cron RQ, Davi S, Minoia F, Ravelli A. Clinical features and correct diagnosis of macrophage activation syndrome. Expert Rev Clin Immunol 2015; 11: 1043–1053, DOI: 10.1586/1744666X.2015.1058159.
20.
Ravelli A, Minoia F, Davì S, et al. 2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborat. Arthritis Rheumatol 2016; 68: 566–676, DOI: 10.1002/art.39332.
21.
Srirangan S, Choy EH. The role of interleukin 6 in the pathophysiology of rheumatoid arthritis. Ther Adv Musculoskelet Dis 2010; 2: 247–256, DOI: 10.1177/1759720X10378372.
22.
Kim GW, Lee NR, Pi RH, et al. IL-6 inhibitors for treatment of rheumatoid arthritis: past, present, and future. Arch Pharm Res 2015; 38: 575–584, DOI: 10.1007/s12272-015-0569-8.
23.
Okuda Y. Review of tocilizumab in the treatment of rheumatoid arthritis. Biologics 2008; 2: 75–82, DOI: 10.2147/btt.s1828.
24.
Zhang S, Li L, Shen A, et al. Rational use of tocilizumab in the treatment of novel coronavirus pneumonia. Clin Drug Investing 2020; 40: 511–518, DOI: 10.1007/s40261-020-00917-3.
25.
Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol 2014; 6: a016295, DOI: 10.1101/cshperspect.a016295.
26.
Patel A, Shah K, Dharsandiya M, et al. Safety and efficacy of tocilizumab in the treatment of severe acute respiratory syndrome coronavirus-2 pneumonia: a retrospective cohort study. Indian J Med Microbiol 2020; 38: 116–122, DOI: 10.4103/ijmm.IJMM_20_298.
27.
Cortegiani A, Ippolito M, Greco M, et al. Rationale and evidence on the use of tocilizumab in COVID-19: a systematic review. Pulmonology 2021; 27: 52–66, DOI: 10.1016/j.pulmoe.
29.
Fu B, Xu X, Wei H. Why tocilizumab could be an effective treatment for severe COVID-19? J Transl Med 2020; 18: 164, DOI: 10.1186/s12967-020-02339-3.
30.
Turnier JL, Brunner HI. Tocilizumab for treating juvenile idiopathic arthritis. Expert Opin Biol Ther, 16: 4, 559–566, DOI: 10.1517/14712598.2016.1150997.
31.
Vercruysse F, Barnetche T, Lazaro E, et al. Adult-onset Still’s disease biological treatment strategy may depend on the phenotypic dichotomy. Arthritis Res Ther 2019; 21: DOI: 10.1186/s13075-019-1838-6.
32.
Siegler EL, Kenderian SS. Neurotoxicity and cytokine release syndrome after chimeric antigen receptor T-cell therapy: insights into mechanisms and novel therapies. Front Immunol 2020; 11: DOI: 10.3389/fimmu.2020.01973.
33.
Maude SL, Barrett D, Teachey DT, Grupp SA. Managing cytokine release syndrome associated with novel T cell-engaging therapies. Cancer J 2014; 20: 119–122: DOI: 10.1097/PPO. 0000000000000035.
34.
Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood 2014; 124: 188–195, DOI: 10.1182/blood-2014-05-552729 [published correction appears in Blood 2015; 126: 1048, dosage error in article text; published correction appears in Blood 2016; 128: 1533].
35.
Bonifant CL, Jackson HJ, Brentjens RJ, Curran KJ. Toxicity and management in CAR T-cell therapy. Mol Ther Oncolytics 2016; 3: 16011, DOI: 10.1038/mto.2016.11.
36.
Le RQ, Li L, Yuan W, 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: 943–947, DOI: 10.1634/theoncologist.2018-0028.
37.
Klopfenstein T, Zayet S, Lohse A, et al. Impact of tocilizumab on mortality and/or invasive mechanical ventilation requirement in a cohort of 206 COVID-19 patients. Int J Infect Dis 2020; 99: 491–495, DOI: 10.1016/j.ijid.2020.08.024.
38.
Somers EC, Eschenauer GA, Troost JP, et al. Tocilizumab for treatment of mechanically ventilated patients with COVID-19. Clin Infect Dis 2020; 73: e445–e454, DOI: 10.1093/cid/ciaa954.
39.
Albertini L, Soletchnik M, Razurel A, et al. Observational study on off-label use of tocilizumab in patients with severe COVID-19. Eur J Hosp Pharm 2021; 28: 22–27, DOI: 10.1136/ejhpharm-2020-002414.
40.
Yuan X, Mu JS, Mo GX, et al. [Respiratory support for severe 2019-nCoV pneumonia suffering from acute respiratory failure: time and strategy]. Zhonghua Jie He He Hu Xi Za Zhi 2020; 43: 177–180, DOI: 10.3760/cma.j.issn.1001-0939.2020.03.006 [Article in Chinese].
41.
Kataoka H, Kodama F, Tomita T, et al. Immediate amelioration of severe respiratory distress in Sjögren’s syndrome with COVID-19 Treated with a single dose of off-label tocilizumab. Intern Med 2021; 60: 639–643, DOI: 10.2169/internalmedicine. 6010-20.
42.
Kewan T, Covut F, Al-Jaghbeer MJ, et al. Tocilizumab for treatment of patients with severe COVID-19: a retrospective cohort study. EClinicalMedicine 2020; 24: 100418, DOI: 10.1016/j.eclinm.2020.100418.
43.
Ruscitti P, Berardicurti O, Iagnocco A, Giacomelli R. Cytokine storm syndrome in severe COVID-19. Autoimmun Rev 2020; 19: 102562, DOI: 10.1016/j.autrev.2020.102562.
44.
Kaye AG, Siegel R. The efficacy of IL-6 inhibitor tocilizumab in reducing severe COVID-19 mortality: a systematic review. PeerJ 2020; 8: e10322, DOI: 10.7717/peerj.10322.
45.
Boregowda U, Perisetti A, Nanjappa A, et al. Addition of tocilizumab to the standard of care reduces mortality in severe COVID-19: a systematic review and meta-analysis. Front Med (Lausanne) 2020; 7: 586221, DOI: 10.3389/fmed.2020.586221.
46.
Tleyjeh IM, Kashour Z, Damlaj M, et al. Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis. Clin Microbiol Infect 2021; 27: 215–227, DOI: 10.1016/j.cmi.2020.10.036.
47.
Biran N, Ip A, Ahn J, et al. Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study. Lancet Rheumatol 2020; 2: e603–e612, DOI: 10.1016/S2665-9913(20)30277-0.
48.
Carvalho V, Turon R, Goncalves B, et al. Effects of tocilizumab in critically ill patients with COVID-19: a quasi-experimental study. medRxiv 2021. DOI: 10.1101/2020.07.13.20149328 [Preprint].
49.
Guaraldi G, Meschiari M, Cozzi-Lepri A, et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol 2020; 2: e474–e484, DOI: 10.1016/S2665-9913(20)30173-9.
50.
Rosas IO, Bräu N, Waters M, et al. Tocilizumab in hospitalized patients with severe Covid-19 pneumonia. N Engl J Med 2021; 384: 1503–1516, DOI: 10.1056/NEJMoa2028700.
52.
investigators. Efficacy of tocilizumab in patients hospitalized with Covid-19. N Engl J Med 2020; 383: 2333–2344, DOI: 10.1056/NEJMoa2028836.
53.
RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2021; 397: 1637–1645, DOI: 10.1016/S0140-6736(21)00676-0.
54.
Salama C, Han J, Yau L, et al. Tocilizumab in patients hospitalized with Covid-19 pneumonia. N Engl J Med 2021; 384: 20–30, DOI: 10.1056/NEJMoa2030340.
55.
Menzella F, Fontana M, Salvarani C, et al. Efficacy of tocilizumab in patients with COVID-19 ARDS undergoing noninvasive ventilation. Crit Care 2020; 24: 589, DOI: 10.1186/s13054-020-03306-6.
57.
-IL6-receptor tocilizumab use in severe and critical patients affected by coronavirus disease 2019: a comparative analysis.
59.
Stasi C, Fallani S, Voller F, Silvestri C. Treatment for COVID-19: an overview. Eur J Pharmacol 2020; 889: 173644, DOI: 10.1016/j.ejphar.2020.173644.
60.
Hariyanto TI, Kurniawan A. Tocilizumab administration is associated with the reduction in biomarkers of coronavirus disease 2019 infection. J Med Virol 2020; 93: 1832–1836, DOI: 10.1002/jmv.26698.
61.
Moes DJ, van Westerloo DJ, Arend SM, et al. Fixed dosing of tocilizumab in ICU admitted COVID-19 patients is a superior choice compared to bodyweight based dosing; an observational population pharmacokinetic and pharmacodynamic study. medRxiv 2021; 05.10.21256933, DOI: 10.1101/2021.05.10.21256933 [Preprint].
62.
Farooqi F, Dhawan N, Morgan R, et al. Treatment of severe COVID-19 with tocilizumab mitigates cytokine storm and averts mechanical ventilation during acute respiratory distress: a case report and literature review. Trop Med Infect Dis 2020; 5: 112, DOI: 10.3390/tropicalmed5030112.
63.
Tsang HF, Chan LWC, Cho WCS, at al. An update on COVID-19 pandemic: the epidemiology, pathogenesis, prevention and treatment strategies. Expert Rev Anti Infect Ther 2020; 877–888: 1–12, DOI: 10.1080/14787210.2021.1863146.
64.
Matrajt L, Eaton J. Optimizing vaccine allocation for COVID-19 vaccines: critical role of single-dose vaccination. medRxiv 2021; 12.31.20249099, DOI: 10.1101/2020.12.31.20249099 [Preprint].
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