Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in patients with severe COVID-19.
Savino Sciascia, Franco Aprà, Alessandra Baffa, Simone Baldovino, Daniela Boaro, R Boero, Stefano Bonora, Andrea Calcagno, Irene Cecchi, Giacoma Cinnirella, Marcella Converso, Martina Cozzi, Paola Crosasso, Fabio De Iaco, Giovanni Di Perri, Mario Eandi, Roberta Fenoglio, Massimo Giusti, Daniele Imperiale, Gianlorenzo Imperiale, Sergio Livigni, Emilpaolo Manno, Carlo Massara, Valeria Milone, Giuseppe Di Natale, Mauro Navarra, Valentina Oddone, Sara Osella, Pavilio Piccioni, Massimo Radin, Dario Roccatello, Daniela Rossi
Abstract
OBJECTIVES: No agent has yet been proven to be effective for the treatment of patients with severe COVID-19. METHODS: We conducted a pilot prospective open, single-arm multicentre study on off-label use of tocilizumab (TCZ) involving 63 hospitalised adult patients (56 males, age 62.6±12.5) with severe COVID-19. Clinical and laboratory parameters were prospectively collected at baseline, day 1, 2, 7 and 14. No moderate-to-severe adverse events attributable to TCZ were recorded. RESULTS: We observed a significant improvement in the levels of ferritin, C-reactive protein, D-dimer. The ratio of the partial pressure of oxygen (Pa02) to the fraction of inspired oxygen (Fi02) improved (mean±SD Pa02/Fi02 at admission: 152±53; at day 7: 283.73±115.9, at day 14: 302.2±126, p<0.05). The overall mortality was 11%; D-dimer level at baseline, but not IL-6 levels were predictors of mortality. TCZ administration within 6 days from admission in the hospital was associated with an increased likelihood of survival (HR 2.2 95%CI 1.3-6.7, p<0.05). CONCLUSIONS: In hospitalised adult patients with severe COVID-19, TCZ could be a safe option. An improvement in respiratory and laboratory parameters was observed. Future controlled trials in patients with severe illness are urgently needed to confirm the definite benefit with IL-6 target therapy.