In patients hospitalized for COVID-19 pneumonia, treatment with usual care plus namilumab, but not infliximab, was associated with greatly decreased C-reactive protein concentrations as well as improved outcomes, according to the results of a recent study published in Lancet Respiratory Medicine.
Namilumab is an anti-granulocyte-macrophage colony stimulating factor (GM-CSF) monoclonal antibody that has been studied in inflammatory conditions such as rheumatoid arthritis and has a good safety profile. Infliximab is a widely used anti-tumour necrosis factor (TNF) monoclonal antibody, and as such is an important proinflammatory cytokine. Study investigators sought to determine whether the efficacy and safety of these drugs warranted further testing in larger clinical trials. The investigation was based on the hypothesis that recruitment and activation of inflammatory monocytes and macrophages is important in the pathogenesis of severe COVID-19.
This randomized, multicenter, open-label, phase 2 proof-of-concept trial recruited patients hospitalized for COVID-19 pneumonia at 9 hospitals in the United Kingdom. Participants were randomly assigned to groups receiving either usual care (control group), or usual care plus a single intravenous dose of either a 150 mg namilumab or 5 mg/kg infliximab (namilumab or infliximab treatment groups). Among the 299 patients recruited who underwent screening for study inclusion, 146 met the inclusion and exclusion criteria and were enrolled in the study. These 146 patients were then randomized 1:1:1 into usual care (n=54), and groups receiving either namilumab (n=57), or infliximab (n=35). After the administration of namilumab or infliximab, all patients were followed for 28 days. The primary endpoint was improvement in inflammation, measured by C-reactive protein concentrations over time.
The investigators found the probabilities that the interventions were superior to usual care alone in reducing C-reactive protein concentrations over time were 97% for namilumab and 15% for infliximab. Death occurred in 11% of patients in the namilumab group compared with 19% in the usual care group, while 14% of patients died in the infliximab group compared with 15% in the usual care group. Notably, the infliximab trial was “stopped for futility,” said the investigators.
The investigators concluded, “Our trial showed that the addition of namilumab, but not infliximab, to usual care reduced inflammation as measured by CRP concentration in hospitalised patients with COVID-19, compared with usual care alone.” They added that “targeted GM-CSF inhibitors such as namilumab should be further investigated in hospitalised patients with COVID-19.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Fisher BA, Veenith T, Slade D, et al. Namilumab or infliximab compared with standard of care in hospitalised patients with COVID-19 (CATALYST): a randomised, multicentre, multi-arm, multistage, open-label, adaptive, phase 2, proof-of-concept trial. Lancet Respir Med. Published online December 16, 2021. doi:10.1016/S2213-2600(21)00460-4