Tocilizumab and COVID-19: Timing of administration assessment - 01/11/21

Doi : 10.1016/j.idnow.2021.06.304

Q. Richier ^a,^{^{1
Authors contributed equally.},}⁎ , V. Jachiet ^b,^{^{1
Authors contributed equally.}}, V. Bonnemains ^b, L. Plaçais ^c, N. Abisror ^b, M. Garnier ^d, J. Pacanowski ^a, R. Dhote ^e, O. Hinchschberger ^f, M. Michel ^g, B. Bienvenu ^h, C. Comarmond ⁱ, K. Lacombe ^a,^{^{2
Authors contributed equally.}}, A. Mekinian ^b,^{^{2
Authors contributed equally.}}
^a Sorbonne Université, Inserm IPLESP, Service de maladies infectieuses, hôpital Saint-Antoine, AP–HP, 75012 Paris, France
^b Sorbonne Université, AP–HP, Hôpital Saint-Antoine, Service de Médecine Interne and Inflammation-Immunopathology-Biotherapy Department (DMU 3iD), 75012, Paris, France
^c Service de médecine interne et immunologie clinique, hôpital Bicêtre, AP–HP, Paris, France
^d Service d’Anesthésie-réanimation et médecine péri-opératoire, hôpital Saint-Antoine, AP–HP, Sorbonne Université, GRC 29, Paris, France
^e Service de médecine interne, hôpital Avicenne, AP–HP, Paris, France
^f Service de médecine interne, hôpital Emile-Muller, Mulhouse, France
^g Service de médecine interne, hôpital Henri-Mondor, AP–HP, Paris, France
^h Service de Médecine Interne, hôpital Saint-Joseph, Marseille, France
ⁱ Service de médecine interne et immunologie clinique, hôpital Pitié-Salpêtrière, AP–HP, Paris, France

^⁎Corresponding author.

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En prensa. Pruebas corregidas por el autor. Disponible en línea desde el Monday 01 November 2021
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Highlights

•	Recent evidence showed efficacy of tocilizumab in COVID-19 patients.
•	The efficacy of tocilizumab was greater in the subgroup of oxygen-dependent patients, only and if injected within 7 days following symptom onset.
•	This subgroup was highly heterogeneous and precise timing for tocilizumab injection according to the oxygen level remains to be determined.
•	We showed no association between timing of injection after symptom onset and the efficacy of tocilizumab on the mortality rate.
•	In a secondary exploratory analysis, our study suggested that tocilizumab could be less effective when oxygen requirement is >11L/min compared to an earlier administration.
•	However, this hypothesis remains to be verified by administration timing-related randomized clinical trials.

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Abstract

Recent evidence showed greater efficacy of tocilizumab (TCZ) in the subgroups of COVID-19 patients who presented with symptoms for less than 7 days and in those only receiving oxygen. We retrospectively analyzed a compassionate use cohort to determine the best timing for TCZ injection. We showed no association between the timing of injection after symptom onset and the efficacy of TCZ on mortality. We then investigated whether the oxygen level at the time of TCZ injection impacted the mortality rate. Our study finally suggested that TCZ could be less effective when oxygen requirement is >11L/min and we hypothesized that earlier administration could be associated with better outcome. However, randomized clinical trials are required to confirm this hypothesis.

El texto completo de este artículo está disponible en PDF.

Keywords : COVID-19, SARS-CoV-2, Tocilizumab, Timing of administration, Oxygen level