Effect of Sotrovimab on Hospitalization or Death Among High-risk Patients With Mild to Moderate COVID-19
Gupta et al.
, Effect of Sotrovimab on Hospitalization or Death Among High-risk Patients With Mild to Moderate COVID-19
, JAMA, doi:10.1001/jama.2022.2832 (results published 12/4/21), COMET-ICE, NCT04545060
RCT 1,057 outpatients, 529 treated with sotrovimab, showing significantly lower hospitalization >24h or mortality with treatment.Efficacy is variant dependent. In Vitro studies predict lower efficacy for BA.1 [Liu, Sheward, VanBlargan] and a lack of efficacy for BA.2 [Zhou]. US EUA has been revoked.
risk of death, 80.0% lower, RR 0.20, p = 0.50, treatment 0 of 528 (0.0%), control 2 of 529 (0.4%), NNT 264, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 29.
risk of mechanical ventilation, 88.9% lower, RR 0.11, p = 0.12, treatment 0 of 528 (0.0%), control 4 of 529 (0.8%), NNT 132, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm), day 29.
risk of progression, 75.0% lower, RR 0.25, p < 0.001, treatment 7 of 528 (1.3%), control 28 of 529 (5.3%), NNT 25, day 29.
risk of hospitalization >24hrs or death, 79.0% lower, RR 0.21, p < 0.001, treatment 6 of 528 (1.1%), control 30 of 529 (5.7%), NNT 22, day 29, ITT, primary outcome.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Conflicts of interest:
research funding from the drug patent holder, employee of the drug patent holder.
Gupta et al., 4 Dec 2021, Double Blind Randomized Controlled Trial, placebo-controlled, multiple countries, peer-reviewed, 68 authors, average treatment delay 2.6 days, trial NCT04545060 (history)
JAMA | Original Investigation
Effect of Sotrovimab on Hospitalization or Death Among High-risk Patients
With Mild to Moderate COVID-19
A Randomized Clinical Trial
Anil Gupta, MD; Yaneicy Gonzalez-Rojas, MD; Erick Juarez, MD; Manuel Crespo Casal, MD; Jaynier Moya, MD; Diego Rodrigues Falci, MD, PhD;
Elias Sarkis, MD; Joel Solis, MD; Hanzhe Zheng, PhD; Nicola Scott, MSc; Andrea L. Cathcart, PhD; Sergio Parra, MD, MSc; Jennifer E. Sager, PhD;
Daren Austin, PhD; Amanda Peppercorn, MD; Elizabeth Alexander, MD, MSc; Wendy W. Yeh, MD; Cynthia Brinson, MD; Melissa Aldinger, PharmD;
Adrienne E. Shapiro, MD, PhD; for the COMET-ICE Investigators
IMPORTANCE Older patients and those with comorbidities who are infected with SARS-CoV-2
may be at increased risk of hospitalization and death. Sotrovimab is a neutralizing antibody
for the treatment of high-risk patients to prevent COVID-19 progression.
OBJECTIVE To evaluate the efficacy and adverse events of sotrovimab in preventing
progression of mild to moderate COVID-19 to severe disease.
DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial including 1057 nonhospitalized
patients with symptomatic, mild to moderate COVID-19 and at least 1 risk factor for
progression conducted at 57 sites in Brazil, Canada, Peru, Spain, and the US from August 27,
2020, through March 11, 2021; follow-up data were collected through April 8, 2021.
INTERVENTIONS Patients were randomized (1:1) to an intravenous infusion with 500 mg of
sotrovimab (n = 528) or placebo (n = 529).
MAIN OUTCOMES AND MEASURES The primary outcome was the proportion of patients with
COVID-19 progression through day 29 (all-cause hospitalization lasting >24 hours for acute
illness management or death); 5 secondary outcomes were tested in hierarchal order,
including a composite of all-cause emergency department (ED) visit, hospitalization of any
duration for acute illness management, or death through day 29 and progression to severe or
critical respiratory COVID-19 requiring supplemental oxygen or mechanical ventilation.
RESULTS Enrollment was stopped early for efficacy at the prespecified interim analysis.
Among 1057 patients randomized (median age, 53 years [IQR, 42-62], 20% were ⱖ65 years
of age, and 65% Latinx), the median duration of follow-up was 103 days for sotrovimab and
102 days for placebo. All-cause hospitalization lasting longer than 24 hours or death was
significantly reduced with sotrovimab (6/528 [1%]) vs placebo (30/529 [6%]) (adjusted
relative risk [RR], 0.21 [95% CI, 0.09 to 0.50]; absolute difference, –4.53% [95% CI, –6.70%
to –2.37%]; P < .001). Four of the 5 secondary outcomes were statistically significant in favor
of sotrovimab, including reduced ED visit, hospitalization, or death (13/528 [2%] for
sotrovimab vs 39/529 [7%] for placebo; adjusted RR, 0.34 [95% CI, 0.19 to 0.63]; absolute
difference, –4.91% [95% CI, –7.50% to –2.32%]; P < .001) and progression to severe or critical
respiratory COVID-19 (7/528 [1%] for sotrovimab vs 28/529 [5%] for placebo; adjusted RR,
0.26 [95% CI, 0.12 to 0.59]; absolute difference, –3.97% [95% CI, –6.11% to –1.82%];
P = .002). Adverse events were infrequent and similar between treatment groups (22% for
sotrovimab vs 23% for placebo); the most common events were diarrhea with sotrovimab
(n = 8; 2%) and COVID-19 pneumonia with placebo (n = 22; 4%).
CONCLUSIONS AND RELEVANCE Among nonhospitalized patients with mild to moderate
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