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Multicenter Study
. 2022 Jan;28(1):3-10.
doi: 10.1177/17534259211064602. Epub 2022 Jan 28.

Delayed inflammation decrease is associated with mortality in Tocilizumab-treated critically ill SARS-CoV-2 patients: A retrospective matched-cohort analysis

Tomas Urbina  1   2 , Jean-Rémi Lavillegrand  1   2 , Marc Garnier  2   3 , Arsene Mekinian  2   4 , Jerome Pacanowski  5 , Nathalie Mario  6 , Guillaume Dumas  7 , Geoffroy Hariri  1   2 , Antoine Pilon  6 , Lucie Darrivère  3 , Muriel Fartoukh  2   8 , Bertrand Guidet  1   2 , Eric Maury  1   2 , Judith Leblanc  9 , Yannick Chantran  10 , Olivier Fain  2   4 , Karine Lacombe  2   5 , Guillaume Voiriot  2   8 , Hafid Ait-Oufella  1   2   11
Affiliations
Multicenter Study

Delayed inflammation decrease is associated with mortality in Tocilizumab-treated critically ill SARS-CoV-2 patients: A retrospective matched-cohort analysis

Tomas Urbina et al. Innate Immun. 2022 Jan.

Abstract

Little is known about the immuno-inflammatory response to Tocilizumab and its association with outcome in critically-ill SARS-CoV2 pneumonia. In this multicenter retrospective cohort of SARS-CoV-2 patients admitted to three intensive care units between March and April 2020, we matched on gender and SAPS II 21 Tocilizumab-treated patients to 42 non-treated patients. Need for mechanical ventilation was 76% versus 79%. IL-6, C-reactive protein, and fibrinogen had been collected within the first days of admission (T1), 3 d (T2) and 7 d (T3) later. Tocilizumab-treated patients had persistently higher IL-6 plasma levels and persistently lower C-Reactive protein and fibrinogen levels. Among Tocilizumab-treated patients, baseline levels of inflammatory biomarkers were not different according to outcome. Conversely, C-reactive protein and fibrinogen decrease was delayed in non-survivors. C-Reactive protein decreased at T1 in survivors (45 [30-98] vs 170 [69-204] mg/l, P < 0.001) but only at T2 in non-survivors (37 [13-74] vs 277 [235-288], P = 0.03). Fibrinogen decreased at T2 in survivors (4.11 [3.58-4.69] vs 614 [5.61-7.85] g/l, P = 0.005) but not in non-survivors (4.79 [4.12-7.58] vs 7.24 [6.22-9.24] g/l, P = 0.125). Tocilizumab treatment was thus associated with a persistent both increase in plasma IL-6, and decrease in C-reactive protein and fibrinogen. Among Tocilizumab-treated patients, the decrease in inflammatory biomarkers was delayed in non-survivors.

Keywords: C-reactive protein; SARS-CoV-2; Tocilizumab; cytokine; intensive care unit.

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Conflict of interest statement

Declaration of conflicting interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
IL-6 plasma level kinetics in Tocilizumab-treated patients and matched controls. IL-6 expressed in log of pg/ml. P Values from a Mann–Whitney test for IL-6 at T1, T2, and T3 between treated patients and matched controls. T1 was the day of 1st cytokine, CRP, fibrinogen and blood lymphocyte count measurement within the first d of ICU admission, T2 was 3 d later and T3 7 d later.
Figure 2.
Figure 2.
(A) C-Reactive protein and (B) fibrinogen kinetics in Tocilizumab-treated patients and matched controls. P Values from a Mann–Whitney test for C-reactive protein or fibrinogen at T1, T2, and T3 between treated patients and matched controls. T1 was the day of 1st cytokine, CRP, fibrinogen and blood lymphocyte count measurement within the first d of ICU admission, T2 was 3 d later and T3 7 d later.
Figure 3.
Figure 3.
(A) CRP and (B) fibrinogen plasma level kinetics amongst patients treated with Tocilizumab, according to survival. Survival censored at d-60. P Values from a Wilcoxon's paired test for CRP and fibrinogen between different time points amongst respectively survivors and non-survivors in treated patients. Pre-treatment was the day of anti-IL6R injection, T1 was the day of 1st cytokine, CRP, fibrinogen and blood lymphocyte count measurement available in the ICU, T2 was 3 d later and T3 7 d later.
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