In patients with asymptomatic SARS-CoV-2 infection residing with an infected household contact, combination antibody treatment with subcutaneous casirivimab-imdevimab was found to significantly decrease the risk for progression symptomatic COVID-19, according to results of a study published JAMA.
In this randomized, double-blind, placebo-controlled phase 3 trial, researchers enrolled patients with asymptomatic COVID-19 infection from 112 sites in the US, Romania, and Moldova who were residing with a symptomatic infected household contact. Eligible patients included those aged 12 years and older with reverse transcription-quantitative polymerase chain reaction-confirmed asymptomatic COVID-19 infection. All eligible patients were identified within 96 hours after a household contact tested positive for the infection. Patients were randomly assigned in a 1:1 fashion to receive either combination antibody treatment with subcutaneous casirivimab-imdevimab (600 mg each) or placebo (ClinicalTrials.gov, NCT04452318).
Among a total of 314 patients who underwent randomization, 158 received casirivimab-imdevimab and 156 received placebo. Of these patients, the mean age was 41 (range, 12-87) years, 51.6% were women, and 204 were symptomatic and seronegative at baseline and were included in the primary efficacy analysis. The proportion of seronegative patients who progressed to symptomatic COVID-19 within a 28-day efficacy assessment period was the primary endpoint. Secondary endpoints included the number of weeks of symptomatic SARS-CoV-2 infection and the number of weeks of an increased SARS-CoV-2 viral load (>4 log10 copies/mL).
A total of 310 (99.7%) patients completed the 28-day efficacy assessment period. The researchers found that the risk for progression to symptomatic COVID-19 infection was significantly decreased among patients who received casirivimab-imdevimab vs those who received placebo (29% vs 42.3%, respectively; odds ratio, 0.54; 95% CI, 0.30-0.97; P =.04). Of note, the absolute risk difference was -13.3% (95% CI, -26.3 to -0.3). They also found that the number of weeks of symptomatic COVID-19 per 1000 patients was significantly decreased among patients in casirivimab-imdevimab group vs those in the placebo group (895.7 weeks vs 1637.4 weeks; P =.03). Similar results were observed between patients in the casirivimab-imdevimab vs placebo groups in regard to the number of weeks of an increased SARS-CoV-2 viral load per 1000 patients (489.8 weeks vs 811.9 weeks; P =.001).
In regard to adverse events between patients in the casirivimab-imdevimab and placebo groups, 33.5% and 48.1% had 1 or more treatment-emergent adverse events, 25.8% and 39.7% had an adverse event related to COVID-19, and 11% and 16% had an adverse event unrelated to COVID-19, respectively. At day 8, the researchers assessed virologic outcomes and found that patients in the casirivimab-imdevimab group experienced a more rapid decline in SARS-CoV-2 viral load compared with those in the placebo group (adjusted least-squares mean difference, -1.5 log10 copies/mL). In addition, the proportion of patients who required hospitalization or admission to an emergency department was significantly decreased among those in the casirivimab-imdevimab vs placebo groups (0 vs 6)
Study limitations included that patients were recruited from only 3 countries, with the majority recruited from sites in the US, the small sample size, and the small number of non-White patients enrolled. In addition, this study was conducted prior to both the widespread availability of COVID-19 vaccines and the emergence of the Delta and Omicron SARS-CoV-2 variants.
According to the researchers, “[decreases] in progression to symptomatic infection and in other outcomes as observed herein would be of potential clinical relevance for [the] use of monoclonal antibody therapies in [the] early treatment of COVID-19 [infection].”
Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
O’Brien MP, Forleo-Neto E, Sarkar N, et al. Effect of subcutaneous casirivimab and imdevimab antibody combination vs placebo on development of symptomatic COVID-19 in early asymptomatic SARS-CoV-2 infection: A randomized clinical trial. JAMA. Published online January 14, 2022. doi:10.1001/jama.2021.24939