Tocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis
Mathilde Roumier, Romain Paule, Alexandre Vallée, Julien Rohmer, Marie Ballester, Anne-Laure Brun, Charles Cerf, Marie-Laure Chabi, Thierry Chinet, Marie-Alice Colombier, Eric Farfour, Erwan Fourn, Guillaume Géri, David Khau, Ibrahim Marroun, Matthieu Ponsoye, Antoine Roux, Hélène Salvator, Yoland Schoindre, Anne-Gaëlle Si Larbi, Colas Tchérakian, Marc Vasse, Anne Verrat, Benjamin Zuber, Louis-Jean Couderc, Jean-Emmanuel Kahn, Matthieu Groh, Félix Ackermann
Journal of Clinical Immunology, doi:10.1007/s10875-020-00911-6
Background High levels of serum interleukin-6 (IL-6) correlate with disease severity in COVID-19. We hypothesized that tocilizumab (a recombinant humanized anti-IL-6 receptor) could improve outcomes in selected patients with severe worsening COVID-19 pneumonia and high inflammatory parameters. Methods The TOCICOVID study included a prospective cohort of patients aged 16-80 years with severe (requiring > 6 L/min of oxygen therapy to obtain Sp02 > 94%) rapidly deteriorating (increase by ≥ 3 L/min of oxygen flow within the previous 12 h) COVID-19 pneumonia with ≥ 5 days of symptoms and C-reactive protein levels > 40 mg/L. They entered a compassionate use program of treatment with intravenous tocilizumab (8 mg/kg with a maximum of 800 mg per infusion; and if needed a second infusion 24 to 72 h later). A control group was retrospectively selected with the same inclusion criteria. Outcomes were assessed at D28 using inverse probability of treatment weighted (IPTW) methodology. Results Among the 96 patients included (81% male, mean (SD) age: 60 (12.5) years), underlying conditions, baseline disease severity, and concomitant medications were broadly similar between the tocilizumab (n = 49) and the control (n = 47) groups. In the IPTW analysis, treatment with tocilizumab was associated with a reduced need for overall ventilatory support (49 vs. 89%, wHR: 0.39 [0.25-0.56]; p < 0.001). Albeit lacking statistical significance, there was a substantial trend towards a reduction of mechanical ventilation (31% vs. 45%;; p = 0.026). However, tocilizumab did not improve overall survival (wHR = 0.68 [0.31-1.748], p = 0.338). Among the 85 (89%) patients still alive at D28, patients treated with tocilizumab had a higher rate of oxygen withdrawal (82% vs. 73.5%,], p = 0.005), with a shorter delay before being
Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s10875-020-00911-6 . Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Authors' Contributions
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