Effects of Siltuximab Versus Corticosteroids in Preventing COVID-19 Pneumonia Disease Progression: Multicentre, Open-Label, Randomized Clinical Trial

Abstract

In 2020, COVID-19 caused a global health crisis, prompting research efforts and accelerating drug development. As part of this response, we conducted a phase 2b, multicentre, open-label, randomized (1:1) clinical trial to compare the effects of siltuximab versus corticosteroids on disease progression in hospitalized adults with COVID-19 pneumonia. Between April 2020 and January 2021, 82 patients were randomized to receive siltuximab and 80 corticosteroids (20 methylprednisolone and 60 dexamethasone). Median (IQR) age was 61 years (50-72). Nineteen patients allocated to siltuximab were admitted to the intensive care unit compared to eight receiving corticosteroids (p = 0.025). Corticosteroid treatment was independently associated with a higher risk of avoiding intensive care unit admission (2.7; 95% CI, 1.11-6.62), lower risk of requiring mechanical ventilation (0.43; 95% CI, 0.20-0.93) and shorter hospitalization duration (p = 0.008). Mortality was similar between arms (p = 0.675). Twenty-eight patients receiving siltuximab required rescue therapy while only 5 receiving corticosteroids (p < 0.001). Furthermore, patients receiving corticosteroids had a 53% lower risk of confirmed bacterial or fungal invasive infections (RR 0.47; 95% CI, 0.23-0.95; p = 0.0096). Our results show that initial treatment with corticosteroids was more effective than siltuximab in preventing disease progression, reducing intensive care unit admission, mechanical ventilation, with shorter hospital stays, and fewer infection in COVID-19 pneumonia. Despite numerous challenges, these findings provide valuable insights into optimizing therapeutic strategies, supporting corticosteroids as a preferred treatment over siltuximab in this setting.

Keywords: ICU; IL‐6 antagonists; covid‐19; dexamethasone; siltuximab.

FIGURE 1

Patient Flowchart including outcomes for the primary endpoint and the main secondary endpoints.

FIGURE 2

Kaplan–Meier survival analysis: Days from start of treatment to admission to intensive care unit according to randomization groups. Unadjusted hazard ratio (HR) with 95% confidence interval (CI) is shown.

FIGURE 3

Kaplan–Meier survival analysis: Days from initiation of treatment to requiring respiratory support (high flow nasal cannula, non‐invasive mechanical ventilation, invasive mechanical ventilation) according to randomization group. Unadjusted hazard ratio (HR) with 95% confidence interval (CI) is shown.