Real-world Effectiveness of Sotrovimab for the Early Treatment of COVID-19 During SARS-CoV-2 Delta and Omicron Waves in the United States

Abstract

Background Sotrovimab, a recombinant human monoclonal antibody (mAb) against SARS-CoV-2 had US FDA Emergency Use Authorization (EUA) for the treatment of high-risk outpatients with mild-to-moderate COVID-19 from May 26, 2021, to April 5, 2022. The study objective was to evaluate the real-world effectiveness of sotrovimab in reducing the risk of 30-day all-cause hospitalization and/or mortality during the time period when the prevalence of circulating SARS-CoV-2 variants was changing between Delta and Omicron sub-lineages in the US. Methods A retrospective analysis was conducted on de-identified claims data for 1,530,501 patients diagnosed with COVID-19 (ICD-10: U07.1) from September 1, 2021, to April 30, 2022, in the FAIR Health National Private Insurance Claims (FH NPIC®) database. Patients meeting EUA high-risk criteria were identified via pre-specified ICD-10-CM diagnoses in records ≤24 months prior to their first COVID-19 diagnosis and divided into two cohorts based on claimed procedural codes: treated with sotrovimab (″sotrovimab″) and not treated with a mAb (″no mAb″). All-cause hospitalizations and facility-reported all-cause mortality within 30 days of diagnosis (″30-day hospitalization or mortality″) were identified. Multivariable and propensity score-matched Poisson and logistic regressions were conducted to estimate the adjusted relative risk (RR) and odds of 30-day hospitalization or mortality among those treated with sotrovimab compared with those not treated with a mAb. Results Of the high-risk COVID-19 patients identified, 15,633 were treated with sotrovimab and 1,514,868 were not treated with a mAb. Compared with the no mAb cohort, the sotrovimab cohort was older and had a higher proportion of patients across the majority of high-risk conditions. In the no mAb cohort, 84,307 (5.57%) patients were hospitalized and 8,167 (0.54%) deaths were identified, while in the sotrovimab cohort, 418 (2.67%) patients were hospitalized and 13 (0.08%) deaths were identified. After adjusting for potential confounders, high-risk COVID-19 patients treated with sotrovimab had a 55% relative risk reduction of 30-day hospitalization or mortality (RR: 0.45, 95% CI: 0.41,0.49) and an 85% relative risk reduction of 30-day mortality (RR: 0.15, 95% CI: 0.08, 0.29) compared with high-risk patients not treated with a mAb. From September 2021 to April 2022, sotrovimab maintained clinical effectiveness with relative risk reductions of 30-day hospitalization or mortality ranging from 46% to 71%. Stratifying by high-risk condition, sotrovimab-treated patients exhibited statistically significant relative risk reductions of 30-day hospitalization or mortality compared with the no mAb cohort across all high-risk conditions (P<0.0001), ranging from 44% among pregnant women to 70% among patients 65 years and older. Conclusion In this large, US real-world, observational study of high-risk COVID-19 patients with reported diagnosis between September 2021 and April 2022 during the Delta and early Omicron variant waves, treatment with sotrovimab was associated with reduced risk of 30-day all-cause hospitalization and facility-reported mortality compared with no mAb treatment. Sotrovimab clinical effectiveness persisted throughout the months when Delta and early Omicron sub-lineages were the predominant circulating variants in the US, though there was an uncertain RR estimate in April 2022 with wide confidence intervals due to the small sample size. Sotrovimab clinical effectiveness also persisted among all high-risk subgroups assessed.

Characteristics and outcomes of patients with COVID-19 at high-risk of disease progression receiving sotrovimab, oral antivirals or no treatment in England

“…32 Similarly, in an observational study in the US, treatment with sotrovimab was associated with a reduced risk of all-cause hospitalisation and mortality during the predominance of early Omicron variants. 33 This study has several limitations that should be considered. Firstly, the study presents descriptive analyses with no adjustments for differences in patient characteristics between cohorts, meaning that any potential associations may be subject to bias and confounding.…”

“…32 Similarly, in an observational study in the US, treatment with sotrovimab was associated with a reduced risk of all-cause hospitalisation and mortality during the predominance of early Omicron variants. 33…”

“…30 The results of this study compliment other recent real-word studies on early treatments for COVID-19 in the UK. [31][32][33] For example, the findings of a recent publication on the comparative effectiveness of sotrovimab versus molnupiravir in England, conducted using the OpenSAFELY platform, showed that sotrovimab treatment was associated with a significant reduction in risk of severe COVID-19 outcomes in comparison to treatment with molnupiravir during BA.1 (primary analysis) and BA.2 (exploratory analysis) predominance. 31 Moreover, sotrovimab was found to offer a similar level of protection against disease progression in patients with COVID-19 infected with the Omicron BA.1 and BA.2 subvariants.…”

Effectiveness of Sotrovimab in Preventing COVID-19-related Hospitalizations or Deaths Among U.S. Veterans

“…Aggarwal and colleagues examined effectiveness of sotrovimab among high-risk outpatients diagnosed with COVID-19 in Colorado during October 1, 2021 -December 11, 2021 when Delta was the predominant circulating variant and found a 63% lower odds of 28-day all-cause hospitalization and 89% lower odds of 28day all-cause mortality [7] Insurance Claims database found that patients receiving sotrovimab had a 55% lower risk of 30-day hospitalization or mortality (RR 0.45, 95% CI, 0.41 -0.49) and an 85% lower risk of 30-day mortality (RR 0.15, 95% CI, 0.08 -0.29) [18]. Like Aggarwal et al, Cheng et al found reduced, non-significant sotrovimab effectiveness during BA.2 predominance -RR 0.32, 95% CI, 0.04 -2.38 -in April 2022, with 68 doses of sotrovimab dispensed in an eligible population over 117 thousand.…”

Real-world effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab on preventing hospital admission among higher-risk patients with COVID-19 in Wales: a retrospective cohort study

“…The reduction in hospitalisations and deaths found in this study are broadly consistent with published preomicron randomised controlled trials for sotrovimab, 2 molnupiravir, 3 and nirmatrelvirritonavir, 4 despite our study being carried out when omicron was the predominant variant in Wales. Similar results were observed in real-world studies of nirmatrelvir-ritonavir 22 where a significant decrease in the rate of severe COVID-19 or death was observed with an adjusted HR of 0.54 (95%CI: 0.39-0.75) when omicron was the predominant variant, a preprint study of sotrovimab with a 55% relative risk (RR) reduction of hospitalisation (RR: 0.45, 95%CI: 0.41-0.49) before 23 and a study of sotrovimab with a 72% reduction in risk of hospitalisation (OR: 0.28, 95%CI: 0.11-0.71) after the emergence of omicron variants. 24 Our results contrast to those of the recently published 25,000 participant, prospective, openlabel, UK-wide, PANORAMIC trial, which found only a 1% risk of all-cause hospitalisation and that molnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among adults over 50 years of age or over 18 with other risk factors, in the community.…”