Background: Tocilizumab, a humanized monoclonal antibody, targets IL-6 receptors blocking downstream pro-inflammatory effects of IL-6. In preliminary reports it was suggested to be beneficial in patients with severe COVID-19. Methods: In this open-label prospective study we describe clinical characteristics and outcome of 51 patients hospitalized with confirmed and severe COVID-19 pneumonia treated with tocilizumab intravenously. All patients had elevated IL-6 plasma level (>40 pg/mL) and oxygen saturation <93% in ambient air. Clinical outcomes, oxygen support, laboratory data and adverse events were collected over a follow-up of 30 days. Results: Forty-five patients (88%) were on high-flow oxygen supplementation, six of whom with invasive ventilation. From baseline to day 7 after tocilizumab we observed a dramatic drop of body temperature and CRP value with a significant increase in lymphocyte count (p<0.001). Over a median follow-up time of 34 days from tocilizumab, 34 patients (67%) showed an improvement in their clinical severity class; 31 were discharged; 17 (33%) showed a worsening of their clinical status, of these 14 died (27%). The mortality rate was significantly associated with mechanical ventilation at baseline (83.3% vs 20% of patients on non-invasive oxygen support; p=0.0001). The most frequent side effects were an increase of hepatic enzymes (29%), thrombocytopenia (14%), and serious bacterial and fungal infections (27%). Conclusion: Tocilizumab exerts a rapidly beneficial effect on fever and inflammatory markers, although no significant impact on the clinical outcome can be inferred by our results. Critically ill patients seem to have a high risk of serious infections with this drug.

Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in Milan, Italy / V. Morena, L. Milazzo, L. Oreni, G. Bestetti, T. Fossali, C. Bassoli, A. Torre, M.V. Cossu, C. Minari, E. Ballone, A. Perotti, D. Mileto, F. Niero, S. Merli, A. Foschi, S. Vimercati, G. Rizzardini, S. Sollima, L. Bradanini, L. Galimberti, R. Colombo, V. Micheli, C. Negri, A.L. Ridolfo, L. Meroni, M. Galli, S. Antinori, M. Corbellino. - In: EUROPEAN JOURNAL OF INTERNAL MEDICINE. - ISSN 0953-6205. - 76(2020 Jun), pp. 36-42. [10.1016/j.ejim.2020.05.011]

Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in Milan, Italy

Morena V.;Bestetti G.;Fossali T.;Bassoli C.;Torre A.;Cossu M. V.;Minari C.;Ballone E.;Mileto D.;Merli S.;Foschi A.;Vimercati S.;Bradanini L.;Micheli V.;Galli M.;Antinori S.;
2020-06

Abstract

Background: Tocilizumab, a humanized monoclonal antibody, targets IL-6 receptors blocking downstream pro-inflammatory effects of IL-6. In preliminary reports it was suggested to be beneficial in patients with severe COVID-19. Methods: In this open-label prospective study we describe clinical characteristics and outcome of 51 patients hospitalized with confirmed and severe COVID-19 pneumonia treated with tocilizumab intravenously. All patients had elevated IL-6 plasma level (>40 pg/mL) and oxygen saturation <93% in ambient air. Clinical outcomes, oxygen support, laboratory data and adverse events were collected over a follow-up of 30 days. Results: Forty-five patients (88%) were on high-flow oxygen supplementation, six of whom with invasive ventilation. From baseline to day 7 after tocilizumab we observed a dramatic drop of body temperature and CRP value with a significant increase in lymphocyte count (p<0.001). Over a median follow-up time of 34 days from tocilizumab, 34 patients (67%) showed an improvement in their clinical severity class; 31 were discharged; 17 (33%) showed a worsening of their clinical status, of these 14 died (27%). The mortality rate was significantly associated with mechanical ventilation at baseline (83.3% vs 20% of patients on non-invasive oxygen support; p=0.0001). The most frequent side effects were an increase of hepatic enzymes (29%), thrombocytopenia (14%), and serious bacterial and fungal infections (27%). Conclusion: Tocilizumab exerts a rapidly beneficial effect on fever and inflammatory markers, although no significant impact on the clinical outcome can be inferred by our results. Critically ill patients seem to have a high risk of serious infections with this drug.
COVID-19; IL-6 inhibitors; tocilizumab; Antiviral Agents; Betacoronavirus; Female; Fever; Humans; Italy; Lymphocyte Count; Male; Middle Aged; Outcome and Process Assessment, Health Care; Receptors, Interleukin-6; Respiration, Artificial; Retrospective Studies; Antibodies, Monoclonal, Humanized; Coronavirus Infections; Pandemics; Pneumonia, Viral; Respiratory Insufficiency
Settore MED/17 - Malattie Infettive
21-mag-2020
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/771260
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