Challenges in Translating Recent RCTs on Endovascular Therapy for Large Core Infarctions Into Real-World Practice

将近期关于大面积梗死血管内治疗的随机对照试验结果转化为实际应用的挑战

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Abstract

BACKGROUND: The emergence of SARS-CoV-2 led to the development of therapeutic monoclonal antibodies (mAbs) including sotrovimab, casirivimab/imdevimab (REGEN-COV) and tixagevimab/cilgavimab (EVUSHELD). While tixagevimab/cilgavimab was not approved in the United States for COVID-19 treatment, there was limited off-label use in Singapore based on promising results from the TACKLE trial. The effectiveness of these mAbs against Omicron variants is uncertain. [Figure: see text] METHODS: This is a retrospective cohort study of hospitalized COVID-19 patients treated with mAbs from August 2021 to July 2022, who were matched with a control group at a ratio of 1:3 using propensity score matching (PSM). Characteristics used in PSM included age, gender, vaccination status, comorbidities and use of other treatment modalities ±7 days of 1st PCR positive. Firth’s Logistic regression was used to estimate the effectiveness of mAb in reducing severe COVID-19 outcomes. Patients were stratified by the years 2021 and 2022 to distinguish the Delta and Omicron variants. [Figure: see text] RESULTS: A total of 366 patients were treated with mAbs: 251 patients received sotrovimab, 83 tixagevimab/cilgavimab, and 32 casirivimab/imdevimab. Our analysis suggested an overall lower rate of severe COVD-19 outcome including oxygen use and composite outcomes of high flow oxygen ( >4L), Intensive Care Unit (ICU) admission, or mortality when treated with mAbs (Table 1). However, these differences were not statistically significant, except for a lower oxygen use in patients treated with sotrovimab in 2022. Among 93 patients treated with sotrovimab in 2022, 91.4% did not require oxygen use compared to 81.0% not on sotrovimab (p=0.02). When comparing sotrovimab use for Omicron variant in 2022 with the Delta variant in 2021 (n=158), a lower rate of oxygen use (p< 0.001) and composite outcomes (p=0.043) were observed (Table 2). Analysis between sotrovimab and tixagevimab/cilgavimab showed no significant difference in overall effectiveness. [Figure: see text] CONCLUSION: Despite reduced in vitro neutralization of Omicron subvariants, there was evidence of improved outcomes among patients who received Sotrovimab. Given the potential for the re-emergence of susceptibility as SARS-CoV-2 continues to evolve, mAbs may continue to serve as a valuable component of the armamentarium. DISCLOSURES: Barnaby Edward Young, MB BChir, PhD, Astra Zeneca: Honoraria|Gilead: Honoraria|Moderna: Honoraria|Pfizer: Honoraria|Sanofi: Grant/Research Support|Sanofi: Honoraria Shawn Vasoo, MBBS, MRCP, D(ABP), D(ABIM) (Inf Dis), FRCPath, bioMerieux: In-kind, for this study|Rosco Diagnostica: In-kind, for this study

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