Comparative effectiveness of sotrovimab versus no treatment in non-hospitalised high-risk patients with COVID-19 in North West London: a retrospective cohort study using the Discover dataset

Introduction There is uncertainty regarding how in vitro antibody neutralisation activity translates to the clinical efficacy of sotrovimab against severe acute respiratory syndrome coronavirus 2, although real-world evidence has demonstrated continued effectiveness during both BA.2 and BA.5 predominance. We previously reported descriptive results from the Discover dataset for patients treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or patients at highest risk per National Health Service (NHS) criteria but who were untreated. This study sought to assess the effectiveness of sotrovimab compared with no early coronavirus disease 2019 (COVID-19) treatment in highest-risk patients with COVID-19. Methods Retrospective cohort study using the Discover dataset in North West London. Patients had to be non-hospitalised at index, aged ≥12 years old and meet ≥1 of the NHS highest-risk criteria for receiving early COVID-19 treatment with sotrovimab. The primary objective was to assess the risk of COVID-19-related hospitalisation and/or COVID-19-related death within 28 days of the observed/imputed treatment date between patients treated with sotrovimab and highest-risk patients who received no early COVID-19 treatment. We also performed subgroup analyses for patients aged <65 and ≥65 years, patients with renal dysfunction, and by Omicron subvariant prevalence period (BA.1/2 emergence: 1 December 2021–12 February 2022 [period 1]; BA.2 reaching and at its peak: 13 February–31 May 2022 [period 2]; BA.2 falling and BA.4/5 emergence: 1 June–31 July 2022 [period 3]). Inverse probability of treatment weighting based on propensity scores was used to adjust for measured known and likely confounders between the cohorts. Cox proportional hazards models with stabilised weights were performed to assess hazard ratios (HRs). Results A total of 599 highest-risk patients treated with sotrovimab and 5,191 untreated highest-risk patients were included. Compared with untreated patients, sotrovimab treatment reduced the risk of COVID-19 hospitalisation or death by 50% (HR=0.50; 95% confidence interval [CI] 0.24, 1.06); however, statistical significance was not reached (p=0.07). In addition, sotrovimab reduced the risk of COVID-19 hospitalisation by 57% (HR=0.43; 95% CI 0.18, 1.00) compared with the untreated group, although also not statistically significant (p=0.051). Among patients aged ≥65 years and patients with renal disease, sotrovimab treatment was associated with a significantly reduced risk of COVID-19 hospitalisation, by 89% (HR=0.11; 95% CI 0.02, 0.82; p=0.03) and 82% (HR=0.18; 95% CI 0.05, 0.62; p=0.007), respectively. In period 1, sotrovimab treatment was associated with a 75% lower risk of COVID-19 hospitalisation or death compared with the untreated group (HR=0.25; 95% CI 0.07, 0.89; p=0.032). In periods 2 and 3, HRs of COVID-19 hospitalisation or death were 0.53 (95% CI 0.14, 2.00; p=0.35) and 0.78 (95% CI 0.23, 2.69; p=0.69), respectively, for the sotrovimab versus untreated groups, but differences were not statistically significant. Conclusions Sotrovimab treatment was associated with a significant reduction in risk of COVID-19 hospitalisation in patients aged ≥65 years and those with renal disease compared with the untreated cohort. For the overall cohort, the risk of hospitalisation following sotrovimab treatment was also lower compared with the untreated group; however, this did not achieve statistical significance (p=0.051). The risk of hospitalisation and/or death was lower for the sotrovimab-treated cohort across all time periods but did not reach significance for periods 2 and 3. ### Competing Interest Statement Myriam Drysdale, Daniel C. Gibbons, Emily J. Lloyd, William Kerr and Helen J. Birch are employees of, and/or shareholders in, GSK. Vishal Patel was an employee of GSK at the time of the study and is now an employee of KVM Analytics. Evgeniy R. Galimov, Marcus J. Yarwood, Jonathan D. Watkins, Sophie Young, Benjamin F. Pierce and Tahereh Kamalati are (or were at time of study) employees of Imperial College Health Partners, which received funding from GSK and Vir Biotechnology, Inc to conduct the study. Bethany Levick is an employee of OPEN Health, which received funding from GSK and Vir Biotechnology, Inc to conduct the study. A consultancy fee was paid to the institutional account of Stephen J. Brett. ### Funding Statement This study was funded by GSK in collaboration with Vir Biotechnology, Inc (study number 219543). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Discover Data Research Access Group (DRAG) which has derogated powers to approve studies under its overarching approval as a Health Research Database. Ethics approval for the use of the Discover Platform for research was obtained from the West Midlands, Solihull HRA research ethics committee (reference 18/WM/0323, Integrated Research Application System project ID 253449). This study complies with all applicable laws regarding subject privacy. Data were aggregated and counts less than five were suppressed in line with information governance suppression rules. No direct subject contact or primary collection of individual human subject data occurred. Study results were in tabular form and aggregate analyses that omit subject identification, therefore informed consent, ethics committee or institutional review board approval were not required. Any publications and reports do not include subject identifiers. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The Discover data that support the findings of this study are available from Imperial College Health Partners via approval from the DRAG under certain restrictions.