Effect of Sotrovimab on Hospitalization or Death Among High-risk Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial

• Published in: JAMA : the journal of the American Medical Association Vol. 327; no. 13; pp. 1236 - 1246
• Main Authors: Gupta, Anil, Gonzalez-Rojas, Yaneicy, Juarez, Erick, Crespo Casal, Manuel, Moya, Jaynier, Rodrigues Falci, Diego, Sarkis, Elias, Solis, Joel, Zheng, Hanzhe, Scott, Nicola, Cathcart, Andrea L, Parra, Sergio, Sager, Jennifer E, Austin, Daren, Peppercorn, Amanda, Alexander, Elizabeth, Yeh, Wendy W, Brinson, Cynthia, Aldinger, Melissa, Shapiro, Adrienne E
• Format: Journal Article
• Language: English
• Published: United States American Medical Association 05.04.2022
• Subjects: Acute Disease; Adult; Adverse events; Aged; Antibodies; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - therapeutic use; Antibodies, Neutralizing - administration & dosage; Antibodies, Neutralizing - therapeutic use; Antiviral Agents - administration & dosage; Antiviral Agents - therapeutic use; Clinical trials; Comments; Coronaviruses; COVID-19; COVID-19 - mortality; COVID-19 Drug Treatment; Death; Diarrhea; Disease Progression; Emergency medical care; Emergency medical services; Health risks; Health services; Hospitalization; Humans; Illnesses; Infusions, Intravenous; Intravenous administration; Intravenous infusion; Mechanical ventilation; Middle Aged; Monoclonal antibodies; Mortality; Online First; Original Investigation; Patients; Placebos; Respiration, Artificial; Risk analysis; Risk assessment; Risk factors; Risk groups; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Statistical analysis; Treatment Outcome; Viral diseases
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.2022.2832

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 ≥65 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 COVID-19 and at risk of disease progression, a single intravenous dose of sotrovimab, compared with placebo, significantly reduced the risk of a composite end point of all-cause hospitalization or death through day 29. The findings support sotrovimab as a treatment option for nonhospitalized, high-risk patients with mild to moderate COVID-19, although efficacy against SARS-CoV-2 variants that have emerged since the study was completed is unknown. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04545060