| Autor: |
Cristina Mussini, Alessandro Cozzi-Lepri, Marianna Meschiari, Erica Franceschini, Giulia Burastero, Matteo Faltoni, Giacomo Franceschi, Vittorio Iadisernia, Sara Volpi, Andrea Dessilani, Licia Gozzi, Jacopo Conti, Martina Del Monte, Jovana Milic, Vanni Borghi, Roberto Tonelli, Lucio Brugioni, Elisa Romagnoli, Antonello Pietrangelo, Elena Corradini, Massimo Girardis, Stefano Busani, Andrea Cossarizza, Enrico Clini, Giovanni Guaraldi |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Viruses, Vol 15, Iss 2, p 294 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1999-4915 |
| DOI: |
10.3390/v15020294 |
| Popis: |
Background: Treatment guidelines recommend the tocilizumab use in patients with a CRP of >7.5 mg/dL. We aimed to estimate the causal effect of glucocorticoids + tocilizumab on mortality overall and after stratification for PaO2/FiO2 ratio and CRP levels. Methods: This was an observational cohort study of patients with severe COVID-19 pneumonia. The primary endpoint was day 28 mortality. Survival analysis was conducted to estimate the conditional and average causal effect of glucocorticoids + tocilizumab vs. glucocorticoids alone using Kaplan–Meier curves and Cox regression models with a time-varying variable for the intervention. The hypothesis of the existence of effect measure modification by CRP and PaO2/FiO2 ratio was tested by including an interaction term in the model. Results: In total, 992 patients, median age 69 years, 72.9% males, 597 (60.2%) treated with monotherapy, and 395 (31.8%), adding tocilizumab upon respiratory deterioration, were included. At BL, the two groups differed for median values of CRP (6 vs. 7 mg/dL; p < 0.001) and PaO2/FiO2 ratio (276 vs. 235 mmHg; p < 0.001). In the unadjusted analysis, the mortality was similar in the two groups, but after adjustment for key confounders, a significant effect of glucocorticoids + tocilizumab was observed (adjusted hazard ratio (aHR) = 0.59, 95% CI: 0.38–0.90). Although the study was not powered to detect interactions (p = 0.41), there was a signal for glucocorticoids + tocilizumab to have a larger effect in subsets, especially participants with high levels of CRP at intensification. Conclusions: Our data confirm that glucocorticoids + tocilizumab vs. glucocorticoids alone confers a survival benefit only in patients with a CRP > 7.5 mg/dL prior to treatment initiation and the largest effect for a CRP > 15 mg/dL. Large randomized studies are needed to establish an exact cut-off for clinical use. |
| Databáze: |
Directory of Open Access Journals |
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