Comparison of Dual Monoclonal Antibody Therapies for COVID-19 Evolution: A Multicentric Retrospective Study

Abstract

Background: Neutralizing antibodies targeting the SARS-CoV-2 Spike protein reduce COVID-19-related risk of hospitalization, particularly in high-risk individuals. The COCOPREV-R study aimed to evaluate and compare clinical outcomes in high-risk SARS-CoV-2 patients treated with dual monoclonal antibody therapies and to identify associated virological factors.

Methods: The COCOPREV-R study retrospectively collected real-world data from high-risk patients receiving Bamlanivimab/Etesevimab or Casirivimab/Imdevimab dual monoclonal antibody therapies (22 February 2021 to 15 June 2021).

Results: The study included 1004 patients with COVID-19, of whom 691 received Bamlanivimab/Etesevimab and 313 received Casirivimab/Imdevimab. The alpha variant represented 90.1% of those for whom data were available. The risk of hospitalization within 30 days was lower with Bamlanivimab/Etesevimab (12.7%, CI 95% [9.9-16.3%]) compared to Casirivimab/Imdevimab (28.4%, CI 95% [22.7-35.1%) (p < 0.001). The 30-day mortality rates were comparable between both groups (p = 0.982). Analysis of SARS-CoV-2 PCR negativity showed no difference between the two treatment groups (95.2% [93.0-96.9%] and 93.5% [89.1-96.6%] until day 30, p = 0.851 for Bamlanivimab/Etesevimab and Casirivimab/Imdevimab, respectively). Among persistently positive samples with available sequencing results (n = 43), Spike protein changes occurred only in Bamlanivimab/Etesevimab (42.9%) vs. Casirivimab/Imdevimab (0.0%) groups. Q493R (25.0%) and E484K (12.5%) were the most common mutations selected by Bamlanivimab/Etesevimab in follow-up samples. Other factors (immunodepression, comorbidities, and age) did not appear to be associated with the occurrence of Spike protein mutations.

Conclusions: A higher rate of hospitalization was seen with Casirivimab/Imdevimab (RONAPREVE^®) in comparison with Bamlanivimab/Etesevimab treatment, but with the emergence of Spike mutations only in the Bamlanivimab/Etesevimab group.

Keywords: COVID-19; SARS-CoV-2; immune escape mutation; monoclonal antibody therapy; spike gene.

Figure 1

(A) Probability of hospitalization (COVID-19 cause) at 30 days of treatment administration (Kaplan–Meier method). Patients treated with Casirivimab/Imdevimab had a higher rate of hospitalization 30 days post-infusion (28.4% [22.7–35.1%]) compared to the Bamlanivimab/Imdevimab treatment group (12.7% [9.9–16.3%]). (B) Probability of death (COVID-19 cause) at 30 days of treatment administration (Kaplan–Meier method). The probability of death was low in both dual monoclonal antibody therapy arms. The proportion of deaths due to COVID-19 following infusion of Bamlanivimab/Etesevimab was 2.8% versus 2.0% in patients treated with Casirivimab/Imdevimab. (C) Probability of death (All causes) at 30 days of treatment administration (Kaplan–Meier method). The probability of death from all causes was similar between Bamlanivimab/Etesevimab and Casirivimab/Imdevimab (5.4% vs. 5.5%, p = 0.585)) until 30 days.

Figure 1

(A) Probability of hospitalization (COVID-19 cause) at 30 days of treatment administration (Kaplan–Meier method). Patients treated with Casirivimab/Imdevimab had a higher rate of hospitalization 30 days post-infusion (28.4% [22.7–35.1%]) compared to the Bamlanivimab/Imdevimab treatment group (12.7% [9.9–16.3%]). (B) Probability of death (COVID-19 cause) at 30 days of treatment administration (Kaplan–Meier method). The probability of death was low in both dual monoclonal antibody therapy arms. The proportion of deaths due to COVID-19 following infusion of Bamlanivimab/Etesevimab was 2.8% versus 2.0% in patients treated with Casirivimab/Imdevimab. (C) Probability of death (All causes) at 30 days of treatment administration (Kaplan–Meier method). The probability of death from all causes was similar between Bamlanivimab/Etesevimab and Casirivimab/Imdevimab (5.4% vs. 5.5%, p = 0.585)) until 30 days.

Figure 1

(A) Probability of hospitalization (COVID-19 cause) at 30 days of treatment administration (Kaplan–Meier method). Patients treated with Casirivimab/Imdevimab had a higher rate of hospitalization 30 days post-infusion (28.4% [22.7–35.1%]) compared to the Bamlanivimab/Imdevimab treatment group (12.7% [9.9–16.3%]). (B) Probability of death (COVID-19 cause) at 30 days of treatment administration (Kaplan–Meier method). The probability of death was low in both dual monoclonal antibody therapy arms. The proportion of deaths due to COVID-19 following infusion of Bamlanivimab/Etesevimab was 2.8% versus 2.0% in patients treated with Casirivimab/Imdevimab. (C) Probability of death (All causes) at 30 days of treatment administration (Kaplan–Meier method). The probability of death from all causes was similar between Bamlanivimab/Etesevimab and Casirivimab/Imdevimab (5.4% vs. 5.5%, p = 0.585)) until 30 days.

Figure 2

Analysis of the negativity of COVID-19 PCR tests (survival analysis method with interval-censored data) in the pharmaceutical company database. The proportions of negative PCR tests were similar between Bamlanivimab/Etesevimab and Casirivimab/Imdevimab (95.2% vs. 93.5% p = 0.851).