Tocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis
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ORIGINAL ARTICLE
Tocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis Mathilde Roumier 1 & Romain Paule 1 & Alexandre Vallée 2 & Julien Rohmer 1 & Marie Ballester 3 & Anne-Laure Brun 4 & Charles Cerf 5 & Marie-Laure Chabi 4 & Thierry Chinet 6,7 & Marie-Alice Colombier 1 & Eric Farfour 8 & Erwan Fourn 1 & Guillaume Géri 7,9,10 & David Khau 1 & Ibrahim Marroun 1 & Matthieu Ponsoye 1 & Antoine Roux 7,11 & Hélène Salvator 7,11 & Yoland Schoindre 1 & Anne-Gaëlle Si Larbi 5 & Colas Tchérakian 11 & Marc Vasse 8 & Anne Verrat 3 & Benjamin Zuber 5 & Louis-Jean Couderc 7,11 & Jean-Emmanuel Kahn 7,12 & Matthieu Groh 1 & Félix Ackermann 1 & on behalf of the Foch COVID19 Study Group Received: 15 July 2020 / Accepted: 3 November 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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 Mathilde Roumier and Romain Paule contributed equally to this work. Matthieu Groh and Félix Ackermann are senior co-authors * Félix Ackermann [email protected]
7
Simone Veil Medical Faculty, Université Paris-Saclay, Montigny-le-Bretonneux, France
1
Department of Internal Medicine, Foch Hospital, F-92151 Suresnes, France
8
Department of Clinical Biolo
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