No evidence of tocilizumab treatment efficacy for severe to critical SARS-CoV2 infected patients: Results from a retrospective controlled multicenter study.
Age Factors
Aged
Antibodies, Monoclonal, Humanized
/ therapeutic use
COVID-19
/ diagnosis
Case-Control Studies
Female
Follow-Up Studies
France
/ epidemiology
Hospital Mortality
Humans
Male
Middle Aged
Oxygen
/ administration & dosage
Respiration, Artificial
/ statistics & numerical data
Retrospective Studies
Risk Factors
SARS-CoV-2
/ isolation & purification
Severity of Illness Index
Standard of Care
/ statistics & numerical data
Treatment Outcome
COVID-19 Drug Treatment
Journal
Medicine
ISSN: 1536-5964
Titre abrégé: Medicine (Baltimore)
Pays: United States
ID NLM: 2985248R
Informations de publication
Date de publication:
28 May 2021
28 May 2021
Historique:
received:
12
09
2020
accepted:
26
04
2021
entrez:
25
5
2021
pubmed:
26
5
2021
medline:
1
6
2021
Statut:
ppublish
Résumé
To assess tocilizumab (TCZ) efficacy associated to standard of care (SOC) compared to SOC alone in severe coronavirus associated disease 2019 (COVID-19) patients. In a matched case-control study from 3 French Hospital COVID-19 Departments, 27 patients with severe COVID-19 treated with TCZ and SOC were matched for baseline epidemiological and clinical features and compared to 27 severe COVID-19 patients treated with SOC alone. Baseline characteristics of the study population were comparable between groups. Eleven patients (20%) died. TCZ was not associated with clinical improvement as compared to SOC regarding oxygen-free status (44% vs 63%) and death (18.5% vs 22%), despite a higher decrease of the C-reactive protein at Day 7 (10.7 vs 52 mg/L; P < 10-3). Compared to the 43 patients alive at the end-of follow-up, patients who died were older (78 vs 64 years; P < 10-3), with 82% of them older than 72 years vs only 23% of live patients (P < 10-3). Age (OR = 1.15; 95%CI = 1.04-1.3; P = .008) and age over 72 years (OR) = 14.85; 95%CI = 2.7-80; P = .002) were independently associated with mortality. TCZ in addition to SOC for severe COVID-19 patients did not reduce mortality, subsequent need for invasive mechanical ventilation nor did it shorten the time of oxygen support, despite better control of the inflammatory response. More powerful and randomized controlled trials are warranted to determine if TCZ is effective in the management of COVID-19.
Identifiants
pubmed: 34032722
doi: 10.1097/MD.0000000000026023
pii: 00005792-202105280-00032
pmc: PMC8154429
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
tocilizumab
I031V2H011
Oxygen
S88TT14065
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
e26023Informations de copyright
Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.
Déclaration de conflit d'intérêts
The authors have no funding and conflicts of interest to disclose.
Références
Zhu N, Zhang D, Wang W, et al. Nov coronavirus patients pneumonia China. N Engl J Med 2019;382:727–33.
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.
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;180:934–43. doi:10.1001/jamainternmed.2020.0994.
doi: 10.1001/jamainternmed.2020.0994
Moore JB, June CH. Cytokine release syndrome in severe COVID-19. Science 2020;368:473–4.
McGonagle D, Sharif K, O’Regan A, Bridgewood K. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev 2020;19:102537doi:10.1016/j.autrev.2020.102537.
doi: 10.1016/j.autrev.2020.102537
Hadjadj J, Yatim N, Barnabei L, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science 2020;369:718–24.
Herold T, Jurinovic V, Arnreich C, et al. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol 2020;146:128.e4–36.e4. doi:10.1016/j.jaci.2020.05.008.
doi: 10.1016/j.jaci.2020.05.008
Liu F, Li L, Xu M, et al. Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. J Clin Virol 2020;127:104370doi:10.1016/j.jcv.2020.104370.
doi: 10.1016/j.jcv.2020.104370
Yang Z, Liu J, Zhou Y, Zhao X, Zhao Q, Liu J. The effect of corticosteroid treatment on patients with coronavirus infection: a systematic review and meta-analysis. J Infect 2020;81:e13–20.
Pan H, Peto R, et al. WHO Solidarity Trial Consortium. Repurposed antiviral drugs for Covid-19 – interim who solidarity trial results. N Engl J Med 2021;384:497–511. doi:10.1056/NEJMoa2023184.
doi: 10.1056/NEJMoa2023184
Horby P, Lim WS, et al. RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19 – preliminary report. N Engl J Med 2021;384:693–704. doi:10.1056/NEJMoa2021436.
doi: 10.1056/NEJMoa2021436
Fitzgerald JC, Weiss SL, Maude SL, et al. Cytokine release syndrome after chimeric antigen receptor T cell therapy for acute lymphoblastic leukemia. Crit Care Med 2017;45:124–31.
Xu X, Han M, Li T, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A 2020;117:10970–5.
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;19:102568doi:10.1016/j.autrev.2020.102568.
doi: 10.1016/j.autrev.2020.102568
Sciascia S, Apra F, Baffa A, et al. Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in patients with severe COVID-19. Clin Exp Rheumatol 2020;38:529–32.
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;8:695doi:10.3390/microorganisms8050695.
doi: 10.3390/microorganisms8050695
Lan SH, Lai CC, Huang HT, et al. Tocilizumab for severe COVID-19: a systematic review and meta-analysis. Int J Antimicrob Agents 2020;56:106103doi:10.1016/j.ijantimicag.2020.106103.
doi: 10.1016/j.ijantimicag.2020.106103
Guaraldi G, Meschiari M, Cozzi-Lepri A, et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol 2020;2:474–84.
Somers EC, Eschenauer GA, Troost JP, et al. Tocilizumab for treatment of mechanically ventilated patients with COVID-19. Clin Infect Dis 2020;ciaa954doi:10.1093/cid/ciaa954.
doi: 10.1093/cid/ciaa954
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:e603–12.
Ruan Q, Yang K, Wang W, et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 2020;46:846–8.
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;55:105954doi:10.1016/j.ijantimicag.2020.105954.
doi: 10.1016/j.ijantimicag.2020.105954
Jamilloux Y, Henry T, Belot A, et al. Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions. Autoimmun Rev 2020;19:102567doi:10.1016/j.autrev.2020.102567.
doi: 10.1016/j.autrev.2020.102567
Potere N, Nisio MD, Rizzo G, et al. Low-dose subcutaneous tocilizumab to prevent disease progression in patients with moderate COVID-19 pneumonia and hyperinflammation. Int J Infect Dis 2020;100:421–4. doi:10.1016/j.ijid.2020.07.078.
doi: 10.1016/j.ijid.2020.07.078
Giamarellos-Bourboulis EJ, Netea MG, Rovina N, et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe 2020;27:992–1000.e3.
Klopfenstein T, Zayet S, Lohse A, et al. Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients. Med Mal Infect 2020;50:397–400. doi:10.1016/j.medmal.2020.05.001.
doi: 10.1016/j.medmal.2020.05.001
Campochiaro C, Della-Torre E, Cavalli G, 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.
Ip A, Berry DA, Hansen E, et al. Hydroxychloroquine and tocilizumab therapy in COVID-19 patients – An observational study. PLoS One 2020;15:e0237693doi:10.1371/journal.pone.0237693.
doi: 10.1371/journal.pone.0237693
Salvarani C, Dolci G, Massari M, 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;181:24–31. doi:10.1001/jamainternmed.2020.6615.
doi: 10.1001/jamainternmed.2020.6615
Hermine O, Mariette X, Tharaux P-L, 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. doi:10.1001/jamainternmed.2020.6820.
doi: 10.1001/jamainternmed.2020.6820
Stone JH, Frigault MJ, Serling-Boyd NJ, et al. Efficacy of tocilizumab in patients hospitalized with Covid-19. N Engl J Med 2020;383:2333–44. doi:10.1056/NEJMoa2028836.
doi: 10.1056/NEJMoa2028836
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.
doi: 10.1056/NEJMoa2030340
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:n84doi:10.1136/bmj.n84.
doi: 10.1136/bmj.n84
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;395:1054–62.
Yang X, Yu Y, Xu J, 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;8:475–81. doi:10.1016/S2213-2600(20)30079-5.
doi: 10.1016/S2213-2600(20)30079-5
Banerjee A, Pasea L, Harris S, et al. Estimating excess 1-year mortality associated with the COVID-19 pandemic according to underlying conditions and age: a population-based cohort study. Lancet 2020;395:1715–25.
Williamson E, Walker AJ, Bhaskaran KJ, et al. OpenSAFELY: factors associated with COVID-19-related hospital death in the linked electronic health records of 17 million adult NHS patients. medRxiv 2020 2020.05.06.20092999 LSHTM Data Compass.