Dataset Information

Effectiveness of Casirivimab and Imdevimab Antibody Combination in Immunocompromised Hospitalized Patients With Coronavirus Disease 2019: A Post Hoc Analysis in a Phase 1/2/3 Double-Blind Trial.

ABSTRACT:

Background

Individuals who are immunocompromised (IC) are at high risk for severe coronavirus disease 2019 (COVID-19).

Methods

Post hoc analyses of a double-blind trial conducted prior to Omicron (June 2020-April 2021), in hospitalized patients with COVID-19 assessed viral load, clinical outcomes, and safety of casirivimab plus imdevimab (CAS + IMD) versus placebo in IC versus overall study patients.

Results

Ninety-nine of 1940 (5.1%) patients were IC. IC versus overall patients were more frequently seronegative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies (68.7% vs 41.2%) and had higher median baseline viral loads (7.21 vs 6.32 log₁₀ copies/mL). On placebo, IC versus overall patients had slower viral load declines. CAS + IMD reduced viral load in IC and overall patients; least-squares mean difference versus placebo in time-weighted average change from baseline viral load at day 7 was -0.69 (95% confidence interval [CI], -1.25 to -.14) log₁₀ copies/mL for IC patients and -0.31 (95% CI, -.42 to -.20) log₁₀ copies/mL for overall patients. For IC patients, the cumulative incidence of death or mechanical ventilation at day 29 was lower with CAS + IMD (11.0%) versus placebo (17.2%), consistent with overall patients (15.7% CAS + IMD vs 18.3% placebo). IC and overall patients receiving CAS + IMD exhibited similar rates of treatment-emergent adverse events (30.4% and 26.6%, respectively), grade ≥2 hypersensitivity or infusion-related reactions (1.4% and 2.5%), and deaths (8.7% and 12.2%).

Conclusions

IC patients were more likely to exhibit high viral loads and be seronegative at baseline. For susceptible SARS-CoV-2 variants, CAS + IMD reduced viral load and resulted in fewer death or mechanical ventilation events in IC and overall study patients. There were no new safety findings among IC patients. Clinical Trials Registration. NCT04426695.

SUBMITTER: Somersan-Karakaya S

PROVIDER: S-EPMC10205469 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

Effectiveness of Casirivimab and Imdevimab Antibody Combination in Immunocompromised Hospitalized Patients With Coronavirus Disease 2019: A Post Hoc Analysis in a Phase 1/2/3 Double-Blind Trial.

Somersan-Karakaya Selin S Mylonakis Eleftherios E Mou Jenni J Oviedo-Orta Ernesto E O'Brien Meagan P MP Mas Casullo Veronica V Mahmood Adnan A Hooper Andrea T AT Hussein Mohamed M Ali Shazia S Marty Francisco M FM Forleo-Neto Eduardo E Bhore Rafia R Hamilton Jennifer D JD Herman Gary A GA Hirshberg Boaz B Weinreich David M DM

Open forum infectious diseases 20230419 5

<h4>Background</h4>Individuals who are immunocompromised (IC) are at high risk for severe coronavirus disease 2019 (COVID-19).<h4>Methods</h4>Post hoc analyses of a double-blind trial conducted prior to Omicron (June 2020-April 2021), in hospitalized patients with COVID-19 assessed viral load, clinical outcomes, and safety of casirivimab plus imdevimab (CAS + IMD) versus placebo in IC versus overall study patients.<h4>Results</h4>Ninety-nine of 1940 (5.1%) patients were IC. IC versus overall pat ...[more]

PMID: 37229174

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Project description:IntroductionCasirivimab and imdevimab (CAS/IMV) are two non-competing, high-affinity human IgG1 anti-SARS-CoV-2 monoclonal antibodies, that showed a survival benefit in seronegative hospitalized patients with COVID-19. This study aimed to estimate the day-28 risk of mechanical ventilation (MV) and death in individuals hospitalized for severe COVID-19 pneumonia and receiving CAS/IMV. Additionally, it aimed to identify variables measured at the time of hospital admission that could predict these outcomes and derive a prediction algorithm.MethodsThis is a retrospective, observational cohort study conducted in 12 hospitals in Italy. Adult patients who were consecutively hospitalized from November 2021 to February 2022 receiving CAS/IMV were included. A multivariable logistic regression model was used to identify predictors of MV or death by day 28 from treatment initiation, and β-coefficients from the model were used to develop a risk score that was derived by means of leave-one-out internal cross-validation (CV), external CV, and calibration. Secondary outcome was mortality.ResultsA total of 480 hospitalized patients in the training set and 157 patients in the test set were included. By day 28, 36 participants (8%) underwent MV and 28 died (6%) for a total of 58 participants (12%) experiencing the composite primary endpoint. In multivariable analysis, four factors [age, PaO2/FiO2 ratio, lactate dehydrogenase (LDH), and platelets] were independently associated with the risk of MV/death and were used to generate the proposed risk score. The accuracy of the score in the area under the curve (AUC) was 0.80 and 0.77 in internal validation and test for the composite endpoint and 0.87 and 0.86 for death, respectively. The model also appeared to be well calibrated with the raw data.ConclusionThe mortality risk reported in our study was lower than that previously reported. Although CAS/IMV is no longer used, our score might help in identifying which patients are not likely to benefit from monoclonal antibodies and may require alternative interventions.

Project description:ObjectivesFour peer-reviewed publications have reported results from randomized controlled trials of convalescent plasma for coronavirus disease 2019 infection; none were conducted in the United States nor used standard plasma as a comparator. To determine if administration of convalescent plasma to patients with coronavirus disease 2019 increases antibodies to severe acute respiratory syndrome coronavirus 2 and improves outcome.DesignDouble-blind randomized controlled trial.SettingHospital in New York.PatientsPatients with polymerase chain reaction documented coronavirus disease 2019 infection.InterventionsPatients were randomized (4:1) to receive 2 U of convalescent plasma versus standard plasma. Antibodies to severe acute respiratory syndrome coronavirus 2 were measured in plasma units and in trial recipients.Measurements and main resultsEnrollment was terminated after emergency use authorization was granted for convalescent plasma. Seventy-four patients were randomized. At baseline, mean (sd) Acute Physiology and Chronic Health Evaluation II score (23.4 [5.6] and 22.5 [6.6]), percent of patients intubated (19% and 20%), and median (interquartile range) days from symptom onset to randomization of 9 (6-18) and 9 (6-15), were similar in the convalescent plasma versus standard plasma arms, respectively. Convalescent plasma had high neutralizing activity (median [interquartile range] titer 1:526 [1:359-1:786]) and its administration increased antibodies to severe acute respiratory syndrome coronavirus 2 by 14.4%, whereas standard plasma administration led to an 8.6% decrease (p = 0.005). No difference was observed for ventilator-free days through 28 days (primary study endpoint): median (interquartile range) of 28 (2-28) versus 28 (0-28; p = 0.86) for the convalescent plasma and standard plasma groups, respectively. A greater than or equal to 2 point improvement in the World Health Organization scale was achieved by 20% of subjects in both arms (p = 0.99). All-cause mortality through 90 days was numerically lower in the convalescent plasma versus standard plasma groups (27% vs 33%; p = 0.63) but did not achieve statistical significance. A key prespecified subgroup analysis of time to death in patients who were intubated at baseline was statistically significant; however, sample size numbers were small.ConclusionsAdministration of convalescent plasma to hospitalized patients with coronavirus disease 2019 infection increased antibodies to severe acute respiratory syndrome coronavirus disease 2 but was not associated with improved outcome.

Dataset Information

Effectiveness of Casirivimab and Imdevimab Antibody Combination in Immunocompromised Hospitalized Patients With Coronavirus Disease 2019: A Post Hoc Analysis in a Phase 1/2/3 Double-Blind Trial.

Background

Methods

Results

Conclusions

Publications

Effectiveness of Casirivimab and Imdevimab Antibody Combination in Immunocompromised Hospitalized Patients With Coronavirus Disease 2019: A Post Hoc Analysis in a Phase 1/2/3 Double-Blind Trial.

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