Casirivimab-imdevimab combo may reduce hospitalization in mild-to-moderate COVID-19

29 Sep 2021 byRoshini Claire Anthony
Casirivimab-imdevimab combo may reduce hospitalization in mild-to-moderate COVID-19

Treatment with a combination of the recombinant human IgG1 monoclonal antibodies casirivimab and imdevimab reduced hospitalization rates in high-risk patients with mild-to-moderate COVID-19, according to results of a retrospective study.

“[C]asirivimab-imdevimab treatment of mild-to-moderate COVID-19 was associated with a statistically significant decrease in the rate of all-cause hospitalization during the first 28 days after infusion,” noted the authors.

The study was conducted between December 4, 2020 and April 9, 2021 at Mayo Clinic sites in four US states. Participants were 696 high-risk* adult outpatients (median age 63 years, 51.4 percent female) with mild-to-moderate PCR-confirmed COVID-19 who, within 10 days of symptom onset (median 2 days between PCR test and infusion), received 1-hour infusions of casirivimab (1,200 mg) and imdevimab (1,200 mg). They were propensity score matched with 696 patients with mild-to-moderate COVID-19 who did not receive monoclonal antibody treatment.

About 45 percent of patients were aged 65 years. The most common high-risk factors were hypertension (52.4 percent), BMI 35 kg/m2 (31.0 percent), diabetes mellitus (24.6 percent), chronic lung or renal disease (22.1 and 11.4 percent, respectively), congestive heart failure (6.6 percent), and immunocompromise (6.7 percent).

All-cause hospitalization at day 28 was significantly reduced among patients treated with casirivimab-imdevimab compared with the control cohort (1.6 percent vs 4.8 percent; absolute difference, 3.2 percent, 95 percent confidence interval [CI], 1.4–5.1 percent). [EClinicalMedicine 2021;doi:10.1016/j.eclinm.2021.101102]

This reduction was evident as early as day 14 (1.3 percent vs 3.3 percent; absolute difference, 2.0 percent, 95 percent CI, 0.5–3.7 percent) and day 21 (1.3 percent vs 4.2 percent; absolute difference, 2.9 percent, 95 percent CI, 1.2–4.7 percent).

This translates to an estimated >110 hospitalization days saved in the first 28 days of follow-up among casirivimab-imdevimab recipients.

All-cause ICU admission rates were low and comparable between the casirivimab-imdevimab and control cohorts (risk difference, 0.15, 0.15, and 0.30 percent at days 14, 21, and 28, respectively).

There were five all-cause deaths, one of which occurred in a casirivimab-imdevimab-treated patient and was possibly COVID-19–related. The four deaths in the control group were attributed to respiratory progression due to COVID-19 (n=2), cerebrovascular accident (n=1), and sudden cardiac death (n=1).

Casirivimab-imdevimab recipients had more hospitalization-free days than those in the control group (eg, number of days in hospital: 0.07 vs 0.23 at day 28).

Seven patients experienced adverse events (AEs), all mild. The AEs included nausea (n=2), shortness of breath (n=2), fever (n=4), and chest pain, headache, or flushing (n=1). There were no incidents of anaphylaxis.

The authors pointed out that the study population was limited to individuals with a high risk of progressing to severe COVID-19 disease, with common high-risk factors including hypertension, obesity, diabetes, and older age.

“[These factors have been identified] as predisposing factors for severe and critical COVID-19,” they said, highlighting the clinical relevance of the low hospitalization rate seen in this study.

The overall low rate of hospitalization in the control group could be due to multiple factors including improved monitoring and testing strategies, they continued.

“[T]his real-world study suggests that when patients who are at high risk due to a range of comorbidities contract a mild or moderate case of COVID-19, this combination of monoclonal injections gives them a chance of a nonhospitalized recovery. In other words, they recover safely at home,” said senior author Professor Raymund Razonable, an infectious diseases specialist from Mayo Clinic in Rochester, Minnesota, US.

Limitations included the retrospective observational study design, predominantly Caucasian population, and use of a single healthcare system. “[The results] must [also] be considered in the face of variable susceptibility of emerging variants in the community,” the authors said.

“Our conclusion overall at this point is that monoclonal antibodies are an important [treatment] option … to reduce the impact of COVID-19 in high-risk patients,” said Razonable.

 

 

 

*High-risk: Age 65 years, BMI 35 kg/m2, diabetes mellitus, chronic kidney disease, immunocompromised, or use of immunosuppressive medications. In patients aged 55 years, hypertension, cardiovascular disease, or chronic lung disease were qualifying criteria.