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

• DOI: 10.1016/j.ejim.2020.05.011
• Publication Date: 2020-05-21T21:54:35Z
• Authors: Valentina Morena; Laura Milazzo; Letizia Oreni; Giovanna Bestetti; Tommaso Fossali; Cinzia Bassoli; Alessandro Torre; Maria Vittoria Cossu; Caterina Minari; Elisabetta Ballone; Andrea Perotti; Davide Mileto; Fosca Niero; Stefania Merli; Antonella Foschi; Stefania Vimercati; Giuliano Rizzardini; Salvatore Sollima; Lucia Bradanini; Laura Galimberti; Riccardo Colombo; Valeria Micheli; Cristina Negri; Anna Lisa Ridolfo; Luca Meroni; Massimo Galli; Spinello Antinori; Mario Corbellino
• Keywords: Male; 0301 basic medicine; 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; Fever; Pneumonia, Viral; Antibodies, Monoclonal, Humanized; Antiviral Agents; Betacoronavirus; 03 medical and health sciences; Internal Medicine; Humans; Lymphocyte Count; Pandemics; Retrospective Studies; SARS-CoV-2; COVID-19; Middle Aged; Receptors, Interleukin-6; Respiration, Artificial; 3. Good health; Outcome and Process Assessment, Health Care; Italy; Original Article; Female; Coronavirus Infections; Respiratory Insufficiency

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.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.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%).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.