Change in Effectiveness of Sotrovimab for Preventing Hospitalization and Mortality in COVID-19 Outpatients During the Omicron Phase

Abstract

Background: Sotrovimab, a neutralizing monoclonal antibody (mAb) treatment authorized for early symptomatic COVID-19 patients, was effective in preventing the progression of severe disease and mortality following SARS-CoV-2 Delta variant infection. It is not known whether sotrovimab is similarly effective for SARS-CoV-2 Omicron variant infection. Methods: Observational cohort study of non-hospitalized adult patients with SARS-CoV-2 infection from December 26, 2021 to March 10, 2022 (>96% Omicron BA.1 variant), using electronic health records from a statewide health system linked to state-level vaccine and mortality data. We used propensity matching to select up to 3 patients not receiving mAbs or other authorized antivirals for each patient who received outpatient sotrovimab treatment. The primary outcome was 28-day hospitalization; secondary outcomes included mortality. To evaluate change in sotrovimab effectiveness during the Omicron phase, we propensity matched sotrovimab-treated patients from Omicron to Delta (October 1-December 11, 2021) phases to each other and then to untreated controls with a treatment-variant interaction added to the logistic regression model. Results: Of 30,247 patients with SARS-CoV-2 infection, we matched 1,542 receiving sotrovimab to 3,663 not receiving treatment. Compared to untreated patients, sotrovimab treatment was not associated with reduced odds of all-cause 28-day hospitalization (raw rate 2.5% versus 3.2%; adjusted OR 0.82, 95% CI 0.55, 1.19) or mortality (raw rate 0.1% versus 0.2%; adjusted OR 0.62, 95% CI 0.07, 2.78). In the combined analysis across Omicron and Delta phases, the observed treatment OR was higher during Omicron than during Delta (OR 0.85 vs. 0.39, respectively; interaction p=0.053) Conclusion: Real-world evidence demonstrated sotrovimab was not associated with reduced hospitalization and all-cause 28-day mortality among COVID-19 outpatients during the Omicron BA.1 phase and attenuated compared to the Delta phase

Efficacy and safety of sotrovimab in patients with COVID‐19: A rapid review and meta‐analysis

“…Data are available online for the included studies. 19,20,[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]…”

Association between treatment failure and hospitalization after receipt of neutralizing monoclonal antibody treatment for COVID-19 outpatients

“…While some mAbs have lost effectiveness due to resistance of newer variants [10,11], other mAb agents and antivirals have maintained effectiveness. When these agents are effective, hospitalization or death (e.g., treatment failure) occurs infrequently but are important outcome measures to understand which patients might be less likely to benefit from mAb therapies.…”

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

“…Among 522 sotrovimab-treated patients PS-matched with 1,563 patients not treated with a mAb, sotrovimab treatment was associated with a 63% (OR: 0.37; 95% CI: 0.19, 0.66) lower odds of 28-day all-cause hospitalization and an 89% (OR: 0.11; 95% CI: 0.0, 0.79) lower odds of 28-day all-cause mortality, similar to our findings during the time period when Delta was the predominant variant (Aggarwal et al, 2022a). A subsequent study using similar methods assessed sotrovimab effectiveness among 5,205 PS-matched high-risk patients between December 26, 2021, and March 10, 2022, and found non-significant lower odds of 28-day all-cause hospitalization (OR: 0.82, 95% CI: 0.55, 1.19) and 28-day all-cause mortality (OR: 0.62, 95% CI: 0.07, 2.78) during the Omicron BA.1 wave (Aggarwal, et al, 2022b). In contrast, our findings showed that sotrovimab maintained statistically significant lower odds of 30-day all-cause hospitalization or mortality between 55%-67% during the December 2021 through March 2022 time period when Omicron BA.1 became the predominant circulating variant.…”

“…Among high-risk subgroups, Aggarwal, et al observed trending towards a lower odds of 28-day hospitalization among patients age ≥65 years (OR: 0.52, 95% CI: 0.30, 0.92), immunocompromised patients (OR: 0.63, 95% CI: 0.38, 1.04), and those with 2 or more comorbid conditions (OR: 0.65, 95% CI: 0.42, 1.01) who were treated with sotrovimab compared with those not treated with a mAb. The non-significant findings from Aggarwal, et al may be due to the smaller sample size and lower power to detect differences between treatment groups (Aggarwal, et al, 2022b).…”