Use of siltuximab in patients with COVID-19 pneumonia requiring ventilatory support
clinical drug discovery/repurposing immunology/immunity
Authors: Giuseppe Gritti et al
Link to paper: https://www.medrxiv.org/content/10.1101/2020.04.01.20048561v1
Journal/ Pre-Print: medRxiv
Key Words: siltuximab, interleukin-6, ARDS, C-Reactive Protein
Research Highlights
1. Observational case control study of use of siltuximab in COVID-19 patients with ARDs
2. 33% patients improved, 43% of patients stabilised and 24% experienced a worsening in their condition
3. CRP levels reduced to normal range following Siltuximab treatment
Summary
Trial of the use of siltuximab, a chimeric mAb that blocks IL-6, in COVID-19 patients who developed pneumonia/ARDS. Preliminary data presented for the first 21 patients treated with siltuximab and followed for up to 7 days show 33% (7/21) patients improved, 43% (9/21) of patients stabilised and 24% (5/21) experienced a worsening in their condition in which 1 patient died, and 1 patient experienced a cerebrovascular event. CRP levels returned to normal levels by day 5 in all patients with sufficient recorded values (100% 16/16). Targeting IL-6 has been identified as a potential strategy to mitigate the complications associated with COVID-19 infection.
Impact for SARS-CoV2/COVID19 research efforts
Treatment of SARS-CoV2/COVID19 positive individuals
Study shows potential role of siltuximab in treating patients with ARDS secondary to SARS-CoV-2 infection
Study Type
· Clinical Cohort study (e.g. drug trials)
Strengths and limitations of the paper
Novelty: Potential use of siltuximab to treat severe COVID-19 infected patients
Standing in the field: IL-6 may play a role in the cytokine storm associated with serious adverse outcomes in patients infected with SARS-CoV-2. Several studies are exploring blockade of IL-6 as a suitable therapeutic target for such patients.
Appropriate statistics: Not applicable
Viral model used: SARS-CoV2 strain
Translatability: Elevated IL-6 levels are associated with severity of disease and lead to ARDS the leading caused of mortality in patients with COVID-19. Direct targeting of IL-6 may improve clinical outcomes in these critically ill patients. Siltuximab is already an FDA-approved drug for other conditions.
Main limitations: Trial not randomised, no control arm, poor outcome, short follow-up period with limited number of patients. However, study is ongoing up to day 30 and further results expected.