Effectiveness of Casirivimab-Imdevimab and Sotrovimab During a SARS-CoV-2 Delta Variant Surge: A Cohort Study and Randomized Comparative Effectiveness Trial.

Autor:	Huang DT; Clinical Research Investigation and Systems Modeling of Acute Illness (CRISMA) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.; Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.; Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., McCreary EK; Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Bariola JR; Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Minnier TE; Wolff Center, University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania., Wadas RJ; Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Shovel JA; Wolff Center, University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania., Albin D; Supply Chain Management/HC Pharmacy, UPMC, Pittsburgh, Pennsylvania., Marroquin OC; Clinical Analytics, UPMC, Pittsburgh, Pennsylvania., Kip KE; Clinical Analytics, UPMC, Pittsburgh, Pennsylvania., Collins K; Clinical Analytics, UPMC, Pittsburgh, Pennsylvania., Schmidhofer M; Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Wisniewski MK; Wolff Center, University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania., Nace DA; Division of Geriatric Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Sullivan C; Clinical Research Investigation and Systems Modeling of Acute Illness (CRISMA) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.; Health System Office of Healthcare Innovation, UPMC, Pittsburgh, Pennsylvania., Axe M; Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Meyers R; Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Weissman A; Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Garrard W; Clinical Analytics, UPMC, Pittsburgh, Pennsylvania., Peck-Palmer OM; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Wells A; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Bart RD; Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.; Health Services Division, UPMC, Pittsburgh, Pennsylvania., Yang A; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Berry LR; Berry Consultants, Austin, Texas., Berry S; Berry Consultants, Austin, Texas., Crawford AM; Berry Consultants, Austin, Texas., McGlothlin A; Berry Consultants, Austin, Texas., Khadem T; Health System Office of Healthcare Innovation, UPMC, Pittsburgh, Pennsylvania., Linstrum K; Clinical Research Investigation and Systems Modeling of Acute Illness (CRISMA) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.; Health System Office of Healthcare Innovation, UPMC, Pittsburgh, Pennsylvania., Montgomery SK; Clinical Research Investigation and Systems Modeling of Acute Illness (CRISMA) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.; Health System Office of Healthcare Innovation, UPMC, Pittsburgh, Pennsylvania., Ricketts D; Clinical Research Investigation and Systems Modeling of Acute Illness (CRISMA) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Kennedy JN; Clinical Research Investigation and Systems Modeling of Acute Illness (CRISMA) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.; Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Pidro CJ; Clinical Research Investigation and Systems Modeling of Acute Illness (CRISMA) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Nakayama A; Health System Office of Healthcare Innovation, UPMC, Pittsburgh, Pennsylvania., Zapf RL; Wolff Center, University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania., Kip PL; Wolff Center, University of Pittsburgh Medical Center (UPMC), Pittsburgh, Pennsylvania., Haidar G; Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Snyder GM; Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., McVerry BJ; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Yealy DM; Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Angus DC; Clinical Research Investigation and Systems Modeling of Acute Illness (CRISMA) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.; Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.; Health System Office of Healthcare Innovation, UPMC, Pittsburgh, Pennsylvania., Seymour CW; Clinical Research Investigation and Systems Modeling of Acute Illness (CRISMA) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.; Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.; Health System Office of Healthcare Innovation, UPMC, Pittsburgh, Pennsylvania.
Jazyk:	angličtina
Zdroj:	JAMA network open [JAMA Netw Open] 2022 Jul 01; Vol. 5 (7), pp. e2220957. Date of Electronic Publication: 2022 Jul 01.
DOI:	10.1001/jamanetworkopen.2022.20957
Abstrakt:	Importance: The effectiveness of monoclonal antibodies (mAbs), casirivimab-imdevimab and sotrovimab, is unknown in patients with mild to moderate COVID-19 caused by the SARS-CoV-2 Delta variant. Objective: To evaluate the effectiveness of mAb against the Delta variant compared with no mAb treatment and to ascertain the comparative effectiveness of casirivimab-imdevimab and sotrovimab. Design, Setting, and Participants: This study comprised 2 parallel studies: (1) a propensity score-matched cohort study of mAb treatment vs no mAb treatment and (2) a randomized comparative effectiveness trial of casirivimab-imdevimab and sotrovimab. The cohort consisted of patients who received mAb treatment at the University of Pittsburgh Medical Center outpatient infusion centers and emergency departments from July 14 to September 29, 2021. Participants were patients with a positive SARS-CoV-2 test result who were eligible to receive mAbs according to emergency use authorization criteria. Exposure: For the trial, patients were randomized to either intravenous casirivimab-imdevimab or sotrovimab according to a system therapeutic interchange policy. Main Outcomes and Measures: For the cohort study, risk ratio (RR) estimates for the primary outcome of hospitalization or death by 28 days were compared between mAb treatment and no mAb treatment using propensity score-matched models. For the comparative effectiveness trial, the primary outcome was hospital-free days (days alive and free of hospitalization) within 28 days after mAb treatment, where patients who died were assigned -1 day in a bayesian cumulative logistic model adjusted for treatment location, age, sex, and time. Inferiority was defined as a 99% posterior probability of an odds ratio (OR) less than 1. Equivalence was defined as a 95% posterior probability that the OR was within a given bound. Results: A total of 3069 patients (1023 received mAb treatment: mean [SD] age, 53.2 [16.4] years; 569 women [56%]; 2046 had no mAb treatment: mean [SD] age, 52.8 [19.5] years; 1157 women [57%]) were included in the prospective cohort study, and 3558 patients (mean [SD] age, 54 [18] years; 1919 women [54%]) were included in the randomized comparative effectiveness trial. In propensity score-matched models, mAb treatment was associated with reduced risk of hospitalization or death (RR, 0.40; 95% CI, 0.28-0.57) compared with no treatment. Both casirivimab-imdevimab (RR, 0.31; 95% CI, 0.20-0.50) and sotrovimab (RR, 0.60; 95% CI, 0.37-1.00) were associated with reduced hospitalization or death compared with no mAb treatment. In the clinical trial, 2454 patients were randomized to receive casirivimab-imdevimab and 1104 patients were randomized to receive sotrovimab. The median (IQR) hospital-free days were 28 (28-28) for both mAb treatments, the 28-day mortality rate was less than 1% (n = 12) for casirivimab-imdevimab and less than 1% (n = 7) for sotrovimab, and the hospitalization rate by day 28 was 12% (n = 291) for casirivimab-imdevimab and 13% (n = 140) for sotrovimab. Compared with patients who received casirivimab-imdevimab, those who received sotrovimab had a median adjusted OR for hospital-free days of 0.88 (95% credible interval, 0.70-1.11). This OR yielded 86% probability of inferiority for sotrovimab vs casirivimab-imdevimab and 79% probability of equivalence. Conclusions and Relevance: In this propensity score-matched cohort study and randomized comparative effectiveness trial, the effectiveness of casirivimab-imdevimab and sotrovimab against the Delta variant was similar, although the prespecified criteria for statistical inferiority or equivalence were not met. Both mAb treatments were associated with a reduced risk of hospitalization or death in nonhospitalized patients with mild to moderate COVID-19 caused by the Delta variant. Trial Registration: ClinicalTrials.gov Identifier: NCT04790786.
Databáze:	MEDLINE
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