Influence of Prednisone on Inflammatory Biomarkers in Community-Acquired Pneumonia: Secondary Analysis of a Randomized Trial

Natalie Raess, Philipp Schuetz, Nicole Cesana-Nigro, Bettina Winzeler, Sandrine A Urwyler, Sabine Schaedelin, Nicolas Rodondi, Manuel R Blum, Matthias Briel, Beat Mueller, Mirjam Christ-Crain, Claudine A Blum, Natalie Raess, Philipp Schuetz, Nicole Cesana-Nigro, Bettina Winzeler, Sandrine A Urwyler, Sabine Schaedelin, Nicolas Rodondi, Manuel R Blum, Matthias Briel, Beat Mueller, Mirjam Christ-Crain, Claudine A Blum

Abstract

Glucocorticoids are frequently prescribed in inflammatory diseases and have recently experienced a boom in the treatment of COVID-19. Small studies have shown an effect of glucocorticoids on inflammatory marker levels, but definitive proof is lacking. We investigated the influence of prednisone on inflammatory biomarkers in a previous multicenter, randomized, placebo-controlled trial that compared a 7-day treatment course of 50-mg prednisone to placebo in patients hospitalized with community-acquired pneumonia. We compared levels of C-reactive protein (CRP), procalcitonin (PCT), leukocyte and neutrophil count between patients with and without glucocorticoid treatment at baseline and on days 3, 5, and 7 and at discharge by Wilcoxon tests and analysis of variance. A total of 356 patient data sets in the prednisone group and 355 in the placebo group were available for analysis. Compared to placebo, use of prednisone was associated with reductions in levels of CRP on days 3, 5, and 7 (mean difference of 46%, P < .001 for each time point). For PCT, no such difference was observed. Leukocyte and neutrophil count were higher in the prednisone group at all time points (mean difference of 27% for leukocytes and 33% for neutrophils, P <.001 for all time points). We conclude that after administration of glucocorticoids in community-acquired pneumonia, patients had lower CRP levels and increased leukocyte and neutrophil count as compared to the placebo group. PCT levels were not different between treatment groups. PCT levels thus may more appropriately mirror the resolution of infection compared to more traditional inflammatory markers.

Keywords: C-reactive protein; biomarkers; glucocorticoids; procalcitonin; respiratory tract infections.

Conflict of interest statement

The authors declare no conflicts of interest in relation to this study. P.S. reports grants from ThermoFisher, bioMerieux, Roche Diagnostics, Nestlé, and Abbott, outside the submitted work.

© 2021 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.

Figures

Figure 1
Figure 1
Study flowchart. ITT, intention‐to‐treat.
Figure 2
Figure 2
(A) Levels of C‐reactive (CRP) protein in placebo and prednisone groups from day 1 to discharge. Values are given as the natural logarithm (ln) of CRP. CRP levels were not different between groups at day 1 (P = .815), but lower in the prednisone group on days 3, 5, and 7 (overall mean difference, −46%; all P < .001). At discharge after day 7, CRP levels did not differ any more (P = .548). (B) Levels of leukocytes in placebo and prednisone groups from day 1 to discharge. Values are given as the ln of leukocytes. Leukocyte count was not different between groups on day 1 (P = .814), but higher in the prednisone group on days 3, 5, and 7 and at discharge (overall mean difference, +27%; all P < .001). (C) Levels of neutrophils in placebo and prednisone groups from day 1 to discharge. Values are given as the ln of neutrophils. Neutrophil cell count on day 1 was not different between groups (P = .491) but significantly higher in the prednisone group on days 3, 5, and 7 and at discharge (overall mean difference, +33%; all P < .001). (D) Levels of procalcitonin in placebo and prednisone groups from day 1 to discharge. Values are given as the ln of procalcitonin. Procalcitonin levels were not significantly different on day 1 (P = .670), day 3 (P = .374), day 5 (P = .135), and at discharge (P = .929), but marginal on day 7 (P = .049).

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