Subcutaneous Monoclonal Antibodies Reduce Hospitalisation, Death in High-Risk Outpatients With Mild to Moderate COVID-19 Symptoms

April 12, 2022

By Denise Baez

Subcutaneously administered casirivimab and imdevimab was associated with reduced hospitalisation and death in high-risk outpatients with mild to moderate coronavirus disease 2019 (COVID-19) symptoms when compared with no treatment, and showed similar outcomes compared with intravenous treatment, according to a study published in JAMA Open Network.

In a cohort study of 1,959 propensity-matched outpatients with mild to moderate COVID-19 symptoms, the 28-day rate of hospitalisation or death was 3.4% among individuals receiving subcutaneous treatment compared with 7% for those receiving no treatment at all.

In a second cohort analysis of 2,185 outpatients, the 28-day rate of hospitalisation or death was 2.8% for subcutaneous treatment compared with 1.7% for intravenous treatment.

“These data suggest that subcutaneous administration of monoclonal antibodies may be a reasonable alternative to intravenous administration for prevention of death, intensive care unit admission, and need for mechanical ventilation,” wrote Erin K. McCreary, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, and colleagues.

The authors also noted that the findings provide preliminary evidence of potential expanded use of subcutaneous monoclonal antibody treatment, particularly in areas that are facing treatment capacity and/or staffing shortages.

The study included high-risk outpatients presenting to a learning health system in the United States with mild to moderate COVID-19 symptoms between July 14, 2021, and October 26, 2021, who were eligible for monoclonal antibody treatment under emergency use authorisation (EUA). Patients received either a subcutaneous injection or intravenous administration of the combined single dose of 600 mg of casirivimab and 600 mg of imdevimab. A non-treated control group of eligible patients was also studied.

Among 1,959 matched adults with mild to moderate COVID-19, 969 patients who received casirivimab and imdevimab subcutaneously had a 28-day rate of hospitalisation or death of 3.4% (22 of 653 patients) compared with 7% (92 of 1306 patients) in the non-treated controls group (risk ratio, 0.48; 95% confidence interval [CI], 0.30-0.80; P = .002).

Among 2,185 patients treated with subcutaneous (n = 969) or intravenous (n = 1,216) casirivimab and imdevimab, the 28-day rate of hospitalisation or death was 2.8% and 1.7%, respectively, which resulted in an adjusted risk difference of 1.5% (95% CI, -0.6% to 3.5%; P = .16).

Among all infusion patients, there was no difference in intensive care unit admission or need for mechanical ventilation.

“To our knowledge, this report is the largest analysis of outpatients with mild to moderate COVID-19 treated with subcutaneously administered monoclonal antibodies compared with non-treated and intravenously administered monoclonal antibodies,” the authors wrote. “These non-causal data indicate a consistent, significant benefit of monoclonal antibody therapy in decreasing hospitalisations and deaths for patients with mild to moderate COVID-19, regardless of route of administration, in a 100% Delta variant landscape.”

“This evidence is promising because administering intravenous monoclonal antibodies is logistically challenging, and healthcare systems across the globe continue to face critical staffing shortages…Subcutaneous administration allows for reduced appointment times (because of elimination of need to place a venous catheter and need to infuse the medication for a certain number of minutes), which increases treatment capacity,” the authors noted. “Indeed, our healthcare system was able to increase the number of patient appointments for monoclonal antibody treatment from 400 to 1,000 patients per week with the same number of staff by changing the route of administration from intravenous to subcutaneous. In addition, under the Public Readiness and Emergency Preparedness Act in the United States, pharmacists are allowed to administer subcutaneous injections, expanding the available staffing pool to much greater capacity. These important gains in practical resources for stressed health systems must be weighed against the absolute risk difference in hospitalisations with subcutaneous administration and intravenous administration, particularly when assessed in relation to lower risk of hospitalisation and death for subcutaneous administration in patients compared with non-treated patients.”


SOURCE: JAMA Network Open