The effect of tixagevimab-cilgavimab on clinical outcomes in patients with COVID-19: A systematic review with meta-analysis

Wang, Yong; Zheng, Jun; Zhu, Kongfu; Wang, Bei; Wang, Daping; Hou, Mengzhuo

doi:10.1016/j.jinf.2022.08.021

Cited by 9 publications

(8 citation statements)

References 7 publications

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“…The findings of our study suggest that PrEP was less effective against Omicron variants than strains of SARS-CoV-2 to which participants were exposed in the pivotal trial. While the difference in proportion of patients reporting symptomatic COVID-19 fell short of statistical significance, the odds ratio was similar to that in published studies, which did observe a statistically significant treatment effect and thus clinical efficacy of PrEP against Omicron variants [13,14].…”

Section: Discussionsupporting

confidence: 82%

Real-World Efficacy of COVID-19 Pre-Exposure Prophylaxis with Tixagevimab/Cilgavimab in People with Multiple Sclerosis

Elias,

Jaber,

Manzano

et al. 2023

Vaccines

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Vaccines against the SARS-CoV-2 virus were authorized for use by the Food and Drug Administration (FDA) in the United States and have proven effective for the prevention of morbidity and death from COVID-19. Certain immunosuppressant medications prevent the development of protective immunity following COVID-19 vaccination. In December 2021, the FDA issued an emergency use authorization (EUA) for a monoclonal-antibody combination of tixagevimab and cilgavimab, under the brand name Evusheld, for pre-exposure prophylaxis (PrEP) against COVID-19 for individuals with moderate-to-severe immune compromise. While a 77% reduction in symptomatic COVID-19 was observed in the PROVENT study, the trial was conducted prior to emergence of the B.1.1.529 Omicron variant. We suspected reduced efficacy of PrEP against Omicron subvariants. We conducted a retrospective cohort study comparing the prevalence of symptomatic COVID-19 infections between 1 January 2022 and 1 July 2022 in eligible patients treated with PrEP versus untreated using a questionnaire administered with the REDCap survey tool. Responses from 235 participants were included in the final analysis, with 176 untreated respondents and 59 in the PrEP cohort. Symptomatic COVID-19 infections were reported in 50 (28.4%) untreated participants and only 9 (15.3%) of those who received PrEP (p = 0.0557; OR 0.4536; 95% CI 0.2046 to 0.9599). Only two participants were hospitalized for COVID-19 infection, both in the untreated cohort. The reduction in COVID-19 infections did not achieve statistical significance, indicating diminished efficacy against Omicron variants.

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Section: Discussionsupporting

confidence: 82%

Real-World Efficacy of COVID-19 Pre-Exposure Prophylaxis with Tixagevimab/Cilgavimab in People with Multiple Sclerosis

Elias,

Jaber,

Manzano

et al. 2023

Vaccines

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“…Recent meta-analysis confirmed the favorable results in a heterogenous mixture of studies, including both pre-exposure prophylaxis and treatment, showing that the overall mortality rate in the Tixagevimab/Cilgavimab-treated group was significantly lower than that in the control group (RR = 0.50, 95% CI: 0.39, 0.64, p < 0.01) [ 73 ]. In addition, protection against COVID-19 was significantly improved in the Tixagevimab/Cilgavimab group compared with the control group (RR = 0.28, 95% CI: 0.15, 0.53, p < 0.01) [ 73 ]. Tixagevimab/Cilgavimab treatment was not associated with the development of serious adverse events in patients (OR = 0.90, 95% CI: 0.67, 1.21, p = 0.48; I 2 = 0%).…”

Section: Therapymentioning

confidence: 93%

Tixagevimab/Cilgavimab in SARS-CoV-2 Prophylaxis and Therapy: A Comprehensive Review of Clinical Experience

Akinosoglou

Rigopoulos

Kaiafa

et al. 2022

Viruses

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Effective treatments and vaccines against COVID-19 used in clinical practice have made a positive impact on controlling the spread of the pandemic, where they are available. Nevertheless, even if fully vaccinated, immunocompromised patients still remain at high risk of adverse outcomes. This has driven the largely expanding field of monoclonal antibodies, with variable results. Tixagevimab/Cilgavimab (AZD7442), a long-acting antibody combination that inhibits the attachment of the SARS-CoV-2 spike protein to the surface of cells, has proved promising in reducing the incidence of symptomatic COVID-19 or death in high-risk individuals without major adverse events when given as prophylaxis, as well as early treatment. Real-world data confirm the antibody combination’s prophylaxis efficacy in lowering the incidence, hospitalization, and mortality associated with COVID-19 in solid organ transplant recipients, patients with immune-mediated inflammatory diseases and hematological malignancies, and patients in B-cell-depleting therapies. Data suggest a difference in neutralization efficiency between the SARS-CoV-2 subtypes in favor of the BA.2 over the BA.1. In treating COVID-19, AZD7442 showed a significant reduction in severe COVID-19 cases and mortality when given early in the course of disease, and within 5 days of symptom onset, without being associated with severe adverse events, even when it is used in addition to standard care. The possibility of the development of spike-protein mutations that resist monoclonal antibodies has been reported; therefore, increased vigilance is required in view of the evolving variants. AZD7442 may be a powerful ally in preventing COVID-19 and the mortality associated with it in high-risk individuals. Further research is required to include more high-risk groups and assess the concerns limiting its use, along the SARS-CoV-2 evolutionary trajectory.

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“…In vitro, cilgavimab-selected variants that expressed Spike protein amino acid substitutions R346G/I, K444E/N/Q/R/T, or N450D were each associated with a >200-fold reduction in susceptibility [3]. The number of articles reporting the effects of tixagevimab/cilgavimab on clinical outcomes in patients with COVID-19 is limited [4][5][6]. In the first genomic surveillance study on tixagevimab/cilgavimab 300/300 mg treatment, Vellas et al found resistance mutations R346X, K444X, and L452R in 73% (9/11) of BA.2-infected solid organ transplant recipients receiving heavy immunosuppression who were followed for up to 14 days [4].…”

Section: Introductionmentioning

confidence: 99%

Treatment-Emergent Cilgavimab Resistance Was Uncommon in Vaccinated Omicron BA.4/5 Outpatients

Gruber,

Tucci,

Rueca

et al. 2023

Biomolecules

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Mutations in the SARS-CoV-2 Spike glycoprotein can affect monoclonal antibody efficacy. Recent findings report the occurrence of resistant mutations in immunocompromised patients after tixagevimab/cilgavimab treatment. More recently, the Food and Drug Agency revoked the authorization for tixagevimab/cilgavimab, while this monoclonal antibody cocktail is currently recommended by the European Medical Agency. We retrospectively reviewed 22 immunocompetent patients at high risk for disease progression who received intramuscular tixagevimab/cilgavimab as early COVID-19 treatment and presented a prolonged high viral load. Complete SARS-CoV-2 genome sequences were obtained for a deep investigation of mutation frequencies in Spike protein before and during treatment. At seven days, only one patient showed evidence of treatment-emergent cilgavimab resistance. Quasispecies analysis revealed two different deletions on the Spike protein (S:del138–144 or S:del141–145) in combination with the resistance S:K444N mutation. The structural and dynamic impact of the two quasispecies was characterized by using molecular dynamics simulations, showing the conservation of the principal functional movements in the mutated systems and their capabilities to alter the structure and dynamics of the RBD, responsible for the interaction with the ACE2 human receptor. Our study underlines the importance of prompting an early virological investigation to prevent drug resistance or clinical failures in immunocompetent patients.

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The effect of tixagevimab-cilgavimab on clinical outcomes in patients with COVID-19: A systematic review with meta-analysis

Cited by 9 publications

References 7 publications

Real-World Efficacy of COVID-19 Pre-Exposure Prophylaxis with Tixagevimab/Cilgavimab in People with Multiple Sclerosis

Real-World Efficacy of COVID-19 Pre-Exposure Prophylaxis with Tixagevimab/Cilgavimab in People with Multiple Sclerosis

Tixagevimab/Cilgavimab in SARS-CoV-2 Prophylaxis and Therapy: A Comprehensive Review of Clinical Experience

Treatment-Emergent Cilgavimab Resistance Was Uncommon in Vaccinated Omicron BA.4/5 Outpatients

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