Tocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis.

Autor: Roumier M; Department of Internal Medicine, Foch Hospital, F-92151, Suresnes, France., Paule R; Department of Internal Medicine, Foch Hospital, F-92151, Suresnes, France., Vallée A; Diagnosis and Therapeutic Center, Hypertension and Cardiovascular Prevention Unit, AP-HP, Hôtel-Dieu Hospital, Paris-Descartes University, Paris, France., Rohmer J; Department of Internal Medicine, Foch Hospital, F-92151, Suresnes, France., Ballester M; Emergency Department, Foch Hospital, F-92151, Suresnes, France., Brun AL; Department of Radiology, Foch Hospital, F-92151, Suresnes, France., Cerf C; Department of Anesthesiology and Intensive Care, Foch Hospital, F-92151, Suresnes, France., Chabi ML; Department of Radiology, Foch Hospital, F-92151, Suresnes, France., Chinet T; Department of Respiratory Medicine, Ambroise Paré Hospital, AP-HP, F-92100, Boulogne-Billancourt, France.; Simone Veil Medical Faculty, Université Paris-Saclay, Montigny-le-Bretonneux, France., Colombier MA; Department of Internal Medicine, Foch Hospital, F-92151, Suresnes, France., Farfour E; Department of Clinical Biology & INSERM UMRS-1176, Foch Hospital, F-92151, Suresnes, France., Fourn E; Department of Internal Medicine, Foch Hospital, F-92151, Suresnes, France., Géri G; Simone Veil Medical Faculty, Université Paris-Saclay, Montigny-le-Bretonneux, France.; Medical Intensive Care Unit, Ambroise Paré Hospital, AP-HP, F-92100, Boulogne-Billancourt, France.; INSERM UMR 1018, Villejuif, France., Khau D; Department of Internal Medicine, Foch Hospital, F-92151, Suresnes, France., Marroun I; Department of Internal Medicine, Foch Hospital, F-92151, Suresnes, France., Ponsoye M; Department of Internal Medicine, Foch Hospital, F-92151, Suresnes, France., Roux A; Simone Veil Medical Faculty, Université Paris-Saclay, Montigny-le-Bretonneux, France.; Department of Respiratory Medicine, Foch Hospital, F-92151, Suresnes, France., Salvator H; Simone Veil Medical Faculty, Université Paris-Saclay, Montigny-le-Bretonneux, France.; Department of Respiratory Medicine, Foch Hospital, F-92151, Suresnes, France., Schoindre Y; Department of Internal Medicine, Foch Hospital, F-92151, Suresnes, France., Si Larbi AG; Department of Anesthesiology and Intensive Care, Foch Hospital, F-92151, Suresnes, France., Tchérakian C; Department of Respiratory Medicine, Foch Hospital, F-92151, Suresnes, France., Vasse M; Department of Clinical Biology & INSERM UMRS-1176, Foch Hospital, F-92151, Suresnes, France., Verrat A; Emergency Department, Foch Hospital, F-92151, Suresnes, France., Zuber B; Department of Anesthesiology and Intensive Care, Foch Hospital, F-92151, Suresnes, France., Couderc LJ; Simone Veil Medical Faculty, Université Paris-Saclay, Montigny-le-Bretonneux, France.; Department of Respiratory Medicine, Foch Hospital, F-92151, Suresnes, France., Kahn JE; Simone Veil Medical Faculty, Université Paris-Saclay, Montigny-le-Bretonneux, France.; Department of Internal Medicine, Ambroise Paré Hospital, AP-HP, F-92100, Boulogne-Billancourt, France., Groh M; Department of Internal Medicine, Foch Hospital, F-92151, Suresnes, France., Ackermann F; Department of Internal Medicine, Foch Hospital, F-92151, Suresnes, France. f.ackermann@hopital-foch.com.
Jazyk: angličtina
Zdroj: Journal of clinical immunology [J Clin Immunol] 2021 Feb; Vol. 41 (2), pp. 303-314. Date of Electronic Publication: 2020 Nov 14.
DOI: 10.1007/s10875-020-00911-6
Abstrakt: 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%; wHR: 0.58 [0.36-0.94]; 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%, wHR = 1.66 [1.17-2.37], p = 0.005), with a shorter delay before being weaned of oxygen therapy (mean 11 vs. 16 days; p < 0.001). At D28, the rate of patients discharged from hospital was higher in the tocilizumab group (70% vs. 40%, wHR = 1.82 [1.22-2.75]; p = 0.003). The levels of CRP and fibrinogen post therapy (p < 0.001 for both variables) were significantly lower in the tocilizumab group (interaction test, mixed model). Rates of neutropenia (35% vs. 0%; p < 0.001) were higher in the tocilizumab group, yet rates of infections (22% vs. 38%, p = 0.089) including ventilator-acquired pneumonia (8% vs. 26%, p = 0.022) were higher in the control group.
Conclusion: These data could be helpful for the design of future trials aiming to counter COVID-19-induced inflammation, especially before patients require admission to the intensive care unit.
Databáze: MEDLINE
Externí odkaz: