Dysregulated inflammation is associated with poor outcomes in Coronavirus disease 2019 (COVID-19). We assessed the efficacy of namilumab, a granulocyte-macrophage colony-stimulating factor inhibitor and infliximab, a tumour necrosis factor inhibitor in hospitalised patients with COVID-19 in order to prioritise agents for phase 3 trials.
In this randomised, multi-arm, parallel group, open label, adaptive phase 2 proof-of-concept trial (CATALYST) we recruited hospitalised patients ≥16 years with COVID-19 pneumonia and C-reactive protein (CRP) ≥40mg/L in nine UK hospitals. Participants were randomly allocated with equal probability to usual care, or usual care plus a single 150mg intravenous dose of namilumab (150mg) or infliximab (5mg/kg). Randomisation was stratified for ward versus ICU. The primary endpoint was improvement in inflammation in intervention arms compared to control as measured by CRP over time, analysed using Bayesian multi-level models. ISRCTN registry number 40580903.
Between 15th June 2020 and 18th February 2021 we randomised 146 participants: 54 to usual care, 57 to namilumab and 35 to infliximab. The probabilities that namilumab and infliximab were superior to usual care in reducing CRP over time were 97% and 15% with point estimates for treatment-time interactions of -0.09 (-0.19, 0.00) and 0.06 (-0.05, 0.17) respectively. Consistent effects were seen in ward and ICU patients and aligned with clinical outcomes, such that the probability of discharge (WHO levels 1-3) at day 28 was 47% and 64% for ICU and ward patients on usual care, versus 66% and 77% for patients treated with namilumab. Death occurred in 6 (11%) and 10 (19%) namilumab and usual care patients respectively, and 4 (14%) and 5 (15%) infliximab and usual care patients respectively. 134 adverse events occurred in 30/55 (55%) namilumab patients compared to 145 in 29/54 (54%) usual care patients. 102 events occurred in 20/29 (69%) infliximab patients versus 112 events in 17/34 (50%) usual care patients.
Namilumab, but not infliximab, demonstrated proof-of-concept evidence for reduction in inflammation in hospitalised patients with COVID-19 pneumonia which was consistent with secondary clinical outcomes. Namilumab should be prioritised for further investigation in COVID-19.
Medical Research Council.
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ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine