Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia
MD Carlo Salvarani, MD Giovanni Dolci, MD Marco Massari, PhD Domenico Franco Merlo, BSc Silvio Cavuto, BSc Luisa Savoldi, MD Paolo Bruzzi, PhD Fabrizio Boni, MD Luca Braglia, BSc Caterina Turrà, MSc Pier Ferruccio Ballerini, MD Roberto Sciascia, MD Lorenzo Zammarchi, MD Ombretta Para, Pier Giorgio Scotton, MD; Walter Omar Inojosa, MD Viviana Ravagnani, MD Nicola Duccio Salerno, Pier Paolo Sainaghi, MD Alessandro Brignone, MD Mauro Codeluppi, MD Elisabetta Teopompi, PhD Maurizio Milesi, MD Perla Bertomoro, MD Norbiato Claudio, MD Mario Salio, MD Marco Falcone, MD Giovanni Cenderello, MD Lorenzo Donghi, Valerio Del Bono, MD Paolo Luigi Colombelli, MD Andrea Angheben, MD Angelina Passaro, MD Giovanni Secondo, MD Renato Pascale, MD Ilaria Piazza, MD Nicola Facciolongo, Massimo Costantini
JAMA Internal Medicine, doi:10.1001/jamainternmed.2020.6615
IMPORTANCE The coronavirus disease 2019 (COVID-19) pandemic is threatening billions of people worldwide. Tocilizumab has shown promising results in retrospective studies in patients with COVID-19 pneumonia with a good safety profile. OBJECTIVE To evaluate the effect of early tocilizumab administration vs standard therapy in preventing clinical worsening in patients hospitalized with COVID-19 pneumonia.
DESIGN, SETTING, AND PARTICIPANTS Prospective, open-label, randomized clinical trial that randomized patients hospitalized between March 31 and June 11, 2020, with COVID-19 pneumonia to receive tocilizumab or standard of care in 24 hospitals in Italy. Cases of COVID-19 were confirmed by polymerase chain reaction method with nasopharyngeal swab. Eligibility criteria included COVID-19 pneumonia documented by radiologic imaging, partial pressure of arterial oxygen to fraction of inspired oxygen (PaO 2 /FIO 2 ) ratio between 200 and 300 mm Hg, and an inflammatory phenotype defined by fever and elevated C-reactive protein. INTERVENTIONS Patients in the experimental arm received intravenous tocilizumab within 8 hours from randomization (8 mg/kg up to a maximum of 800 mg), followed by a second dose after 12 hours. Patients in the control arm received supportive care following the protocols of each clinical center until clinical worsening and then could receive tocilizumab as a rescue therapy.
MAIN OUTCOME AND MEASURES The primary composite outcome was defined as entry into the intensive care unit with invasive mechanical ventilation, death from all causes, or clinical aggravation documented by the finding of a PaO 2 /FIO 2 ratio less than 150 mm Hg, whichever came first. RESULTS A total of 126 patients were randomized (60 to the tocilizumab group; 66 to the control group). The median (interquartile range) age was 60.0 (53.0-72.0) years, and the majority of patients were male (77 of 126, 61.1%). Three patients withdrew from the study, leaving 123 patients available for the intention-to-treat analyses. Seventeen patients of 60 (28.3%) in the tocilizumab arm and 17 of 63 (27.0%) in the standard care group showed clinical worsening within 14 days since randomization (rate ratio, 1.05; 95% CI, 0.59-1.86). Two patients in the experimental group and 1 in the control group died before 30 days from randomization, and 6 and 5 patients were intubated in the 2 groups, respectively. The trial was prematurely interrupted after an interim analysis for futility.
CONCLUSIONS AND RELEVANCE In this randomized clinical trial of hospitalized adult patients with COVID-19 pneumonia and PaO 2 /FIO 2 ratio between 200 and 300 mm Hg who received tocilizumab, no benefit on disease progression was observed compared with standard care. Further blinded, placebo-controlled randomized clinical trials are needed to confirm the results and to evaluate possible applications of tocilizumab in different stages of the disease.
Author Contributions: Drs Dolci and Costantini had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Salvarani and Dolci contributed equally to this article and are co-first authors. Drs Facciolongo and Costantini contributed equally to this article and are co-last authors. Concept and design: Salvarani, Dolci, Massari, Cavuto, Bruzzi, Boni, Turrà, Colombelli,
References
Chen, Wu, Guo, Clinical and immunological features of severe and moderate coronavirus disease 2019, J Clin Invest,
doi:10.1172/JCI137244Guan, Ni, Hu, China Medical Treatment Expert Group for Covid-19. Clinical characteristics of coronavirus disease 2019 in China, N Engl J Med,
doi:10.1056/NEJMoa2002032Horby, Lim, Emberson, Dexamethasone in hospitalized patients with Covid-19-preliminary report, N Engl J Med,
doi:10.1056/NEJMoa2021436Infettive E Tropicali, Croce E Carle, Cuneo, Del Bono
Le, Li, Yuan, FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome, Oncologist,
doi:10.1634/theoncologist.2018-0028Liu, Li, Zhou, Guan, Xiang, Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?, J Autoimmun,
doi:10.1016/j.jaut.2020.102452Manfredi, Cassone, Furini, Tocilizumab therapy in rheumatoid arthritis with interstitial lung disease: a multicenter retrospective study, Intern Med J,
doi:10.1111/imj.14670Mccarthy, Savinelli, Feeney, Tocilizumab therapy in individuals with COVID-19 infection and hyperinflammatory state, Respirology,
doi:10.1111/resp.13912Merlo, Savoldi, Braglia, Emilia, Italy et al., SOC Internistica Multidisciplinare, Ospedale Civile Guastalla, Azienda USL-IRCCS di Reggio Emilia
Price, Altice, Shyr, Tocilizumab treatment for cytokine release syndrome in hospitalized COVID-19 patients: survival and clinical outcomes, Chest. Published online,
doi:10.1016/j.chest.2020.06.006Qin, Zhou, Hu, Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China, Clin Infect Dis,
doi:10.1093/cid/ciaa248Sc Medicina Interna, Ao, Mauriziano, SC Malattie dell'Apparato Respiratorio
Sciascia, Aprà, Baffa, Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in patients with severe COVID-19, Clin Exp Rheumatol
Ss Reumatologia, SC Medicina Interna, DIMET, Università del Piemonte Orientale e AOU Maggiore della Carità di Novara (Sainaghi); Reumatologia
Toniati, Piva, Cattalini, 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,
doi:10.1016/j.autrev.2020.102568Zeng, Huang, Guo, Association of inflammatory markers with the severity of COVID-19: a meta-analysis, Int J Infect Dis,
doi:10.1016/j.ijid.2020.05.055Zhou, Yu, Du, Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study, Lancet,
doi:10.1016/S0140-6736(20)30566-3DOI record:
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