Treatment with neutralizing monoclonal antibody safe and yield positive outcomes in COVID-19 patients: JAMA

The findings, published in JAMA Network Open, suggest that targeted risk stratification strategies may help optimize future nMAb treatment decisions.

The cause of COVID-19, SARS-CoV-2, may lead to severe disease linked with high death and hospitalization rates. Therapy with neutralizing monoclonal antibodies that bind to the spike protein of SARS-CoV-2 has been demonstrated to prevent death and hospitalization n randomized clinical trials (RCTs) of nonvaccinated, nonhospitalized patients at high risk of poor outcomes. The US FDA granted several nMAb therapies emergency use authorization (EUA).

Building on evidence from RCTs, monitoring the safety and effectiveness of nMAb therapies is critical to inform clinical practice and policy recommendations. Therefore, Nalini Ambrose, The MITRE Corporation, Bedford, Massachusetts, and colleagues assessed the safety of four neutralizing monoclonal antibodies products (sotrovimab, casirivimab-imdevimab, bamlanivimab-etesevimab, and bamlanivimab) and their association with adverse outcomes for treatment of COVID-19 in a retrospective cohort study.

The study included 167 183 patients from a consortium of 4 healthcare systems. The patients were nonhospitalized, 12 years and older with a positive COVID-19 infection, and met at least one emergency use authorization criterion for risk of a poor outcome.

The association between treatment with nMAbs and four outcomes were assessed using clinical and SARS-CoV-2 genomic sequence data. The four outcomes included hospitalization, all-cause ED visits, death, and a composite of death and hospitalization within 14 days and 30 days of the index date. Patient index dates were divided into four variant epochs: Omicron BA.1 (January 1 to 31, 2022), Delta and Omicron BA.1 (December 1 to 31, 2021), Delta (July 1 to November 30, 2021), and pre-Delta (November 9, 2020, to June 30, 2021).

The authors reported the following findings:

• Among 167 183 patients, the mean age was 47.0 years; 57.2% were female at birth.
• A total of 25 241 patients received treatment with neutralizing monoclonal antibodies. Treatment with nMAbs was associated with lower odds of hospitalization within 14 days (OR, 0.52), ED visits within 14 days (odds ratio [OR], 0.76), and death within 30 days (OR, 0.14).
• The association between nMAbs and reduced hospitalization risk was more substantial in unvaccinated patients (14-day hospitalization: OR, 0.51). The associations with death and hospitalization were stronger in immunocompromised patients (hospitalization within 14 days: OR, 0.31; death within 30 days: OR, 0.13).
• The strength of associations of nMAbs increased incrementally among patients with a greater probability of poor outcomes; for example, the ORs for hospitalization within 14 days were 0.58 among those in the third (moderate) risk stratum and 0.41 among those in the fifth (highest) risk stratum.
• The association of nMAb treatment with reduced hospitalization risk within 14 days was strongest during the Delta variant epoch (OR, 0.37) but not during the Omicron BA.1 epoch (OR, 1.29). These findings were corroborated in the subset of patients with viral genomic data.
• Treatment with nMAbs was associated with a significant mortality benefit in all variant epochs (Delta: OR, 0.14; pre-Delta: OR, 0.16; Delta and Omicron BA.1: OR, 0.10; and Omicron BA.1: OR, 0.13).
• Potential adverse drug events were identified in 38 treated patients (0.2%

"This study is noteworthy because of its long study period, large sample size, and inclusion of viral genomic data," the researchers wrote.

Reference:

Ambrose N, Amin A, Anderson B, et al. Neutralizing Monoclonal Antibody Use and COVID-19 Infection Outcomes. JAMA Netw Open. 2023;6(4):e239694. doi:10.1001/jamanetworkopen.2023.9694