Effectiveness of Casirivimab-Imdevimab and Sotrovimab During a SARS-CoV-2 Delta Variant Surge
MD, MPH David T Huang, PharmD Erin K Mccreary, MD J Ryan Bariola, MS Tami E Minnier, MD Richard J Wadas, BSN Judith A Shovel, Debbie Albin, MD Oscar C Marroquin, PhD Kevin E Kip, MBA Kevin Collins, MD Mark Schmidhofer, MA Mary Kay Wisniewski, MD David A Nace, MHA Colleen Sullivan, BS Meredith Axe, MBA Russell Meyers, MD; Alexandra Weissman, PhD William Garrard, PhD Octavia M Peck-Palmer, MD, DMSc Alan Wells, MD Robert D Bart, MD Anne Yang, PhD Lindsay R Berry, PhD Scott Berry, PhD Amy M Crawford, PhD Anna Mcglothlin, PharmD Tina Khadem, MS Kelsey Linstrum, MS Stephanie K Montgomery, MET; Daniel Ricketts, MS Jason N Kennedy, BS Caroline J Pidro, MS Anna Nakayama, PhD Rachel L Zapf, PhD Paula L Kip, MD; Ghady Haidar, MD Graham M Snyder, MD; Bryan J Mcverry, MD Donald M Yealy, MD, MPH Derek C Angus, MD, MSc Christopher W Seymour
JAMA Network Open, doi:10.1001/jamanetworkopen.2022.20957
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 (continued) Key Points Question Is monoclonal antibody (mAb) treatment effective in nonhospitalized patients with COVID-19 caused by the Delta variant? Findings In this propensity scorematched cohort study (n = 3069) and randomized comparative effectiveness trial (n = 3558), mAb treatment
Adverse Events Among the 2454 patients who received casirivimab-imdevimab, 17 (<1%) reported adverse events and 7 (<1%) reported severe adverse events, making them rare. Similarly, for the 1104 patients who received sotrovimab, 6 (<1%) reported adverse events and 4 (<1%) reported severe adverse events. The most commonly reported adverse events were flushing, itching, breathing difficulties, and chest tightness or pain.
Discussion During the Delta variant surge, we found that casirivimab-imdevimab and sotrovimab were each associated with a reduced risk-adjusted hospitalization and death among patients with mild to moderate COVID-19 compared with no mAb treatment. In a randomized comparative effectiveness trial, no primary analysis met a prespecified trigger for conclusions of inferiority or equivalence, although the subgroup analysis of patients who received mAb treatment in an infusion center showed superiority of casirivimab-imdevimab over sotrovimab. The Delta variant of SARS-CoV-2 was observed in late 2020 and became the dominant strain worldwide by July 2021. Yet, early evidence of the efficacy of mAb was reported before the emergence of the Delta variant. The present study extended previous work 5 and found that mAbs were associated with improved outcomes in patients with the Delta variant in a cohort with a robust sample size and methods to adjust for treatment selection and confounding. Future work is needed to ascertain the effectiveness of mAbs..
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