Tixagevimab/Cilgavimab for Prevention of COVID-19 during the Omicron Surge: Retrospective Analysis of National VA Electronic Data

Young‐Xu, Yinong; Epstein, Lauren; Marconi, Vincent C.; Davey, Victoria J.; Zwain, Gabrielle; Smith, Jeremy; Korves, Caroline; Cunningham, Fran; Ginde, Adit A.

doi:10.1101/2022.05.28.22275716

Cited by 20 publications

(55 citation statements)

References 29 publications

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“…Pre-emptive monoclonal antibody injections were independent protective factors against SARS-CoV-2 infections during follow-up. A reduced risk of COVID-19 breakthrough infections in immunocompromised patients after passive immunization with tixagevimab/cilgavimab was recently also observed by others [ 64 , 65 ] and further outlines the importance of access to antibody administration for patients with HMs. Nevertheless, analogously to vaccine boosters, monoclonal antibodies also need to be administered repeatedly; based on pharmacokinetic/pharmacodynamic modeling data, the FDA recommends re-administration every 6 months [ 66 ].…”

Section: Discussionsupporting

confidence: 61%

Efficacy of COVID-19 Booster Vaccines in Patients with Hematologic Malignancies: Experiences in a Real-World Scenario

Krekeler

Reitnauer

Bacher

et al. 2022

Cancers

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Background: Two-dose COVID-19 vaccination often results in poor humoral response rates in patients with hematologic malignancies (HMs); yet responses to COVID-19 booster vaccines and the risk of COVID-19 infection post-booster are mostly uncertain. Methods: We included 200 outpatients with HMs and predominantly lymphoid neoplasms (96%, 191/200) in our academic center and reported on the humoral responses, which were assessed by measurement of anti-spike IgG antibodies in peripheral blood as early as 14 days after mRNA-based prime-boost vaccination, as well as factors hampering booster efficacy. Previous basic (double) immunization was applied according to the local recommendations with mRNA- and/or vector-based vaccines. We also report on post-booster COVID-19 breakthrough infections that emerged in the Omicron era and the prophylaxis strategies that were applied to poor and non-responders to booster vaccines. Results: A total of 55% (110/200) of the patients achieved seroconversion (i.e., anti-spike protein IgG antibody titer > 100 AU/mL assessed in median 48 days after prime-boost vaccination) after prime-boost vaccination. Multivariable analyses revealed age, lymphocytopenia, ongoing treatment and prior anti-CD20 B-cell depletion to be independent predictors for booster failure. With each month between anti-CD20-mediated B-cell depletion and booster vaccination, the probability of seroconversion increased by approximately 4% (p < 0.001) and serum–antibody titer (S-AbT) levels increased by 90 AU/mL (p = 0.011). Notably, obinutuzumab treatment was associated with an 85% lower probability for seroconversion after prime-boost vaccination compared to rituximab (p = 0.002). Of poor or non-responders to prime-boost vaccination, 41% (47/114) underwent a second booster and 73% (83/114) underwent passive immunization. COVID-19 breakthrough infections were observed in 15% (29/200) of patients after prime-boost vaccination with predominantly mild courses (93%). Next to seroconversion, passive immunization was associated with a significantly lower risk of COVID-19 breakthrough infections after booster, even in vaccine non-responders (all p < 0.05). In a small proportion of analyzed patients with myeloid neoplasms (9/200), the seroconversion rate was higher compared to those with lymphoid ones (78% vs. 54%, accordingly), while the incidence rate of COVID-19 breakthrough infections was similar (22% vs. 14%, respectively). Following the low frequency of myeloid neoplasms in this study, the results may not be automatically applied to a larger cohort. Conclusions: Patients with HMs are at a high risk of COVID-19 booster vaccine failure; yet COVID-19 breakthrough infections after prime-boost vaccination are predominantly mild. Booster failure can likely be overcome by passive immunization, thereby providing immune protection against COVID-19 and attenuating the severity of COVID-19 courses. Further sophistication of clinical algorithms for preventing post-vaccination COVID-19 breakthrough infections is urgently needed.

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Section: Discussionsupporting

confidence: 61%

Efficacy of COVID-19 Booster Vaccines in Patients with Hematologic Malignancies: Experiences in a Real-World Scenario

Krekeler

Reitnauer

Bacher

et al. 2022

Cancers

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“…It included studies from the United States, France, Israel, Belgium, Spain and the United Kingdom. This review included ten retrospective cohort studies 12,[16][17][18][19][20][22][23][24][25] (including two preprints 16,20 ), six prospective, observational cohort studies [26][27][28][29][30][31] (also including one preprint…”

Section: Resultsmentioning

confidence: 99%

“…Subsequent to the phase 3 study, sixteen real-world post-licensing studies have been performed assessing clinical effectiveness against breakthrough infections. Five were performed in reference to a control group [16][17][18][19][20] , and reported clinical outcomes from propensity-matched U.S. army veterens 16…”

Section: Clinical Effectiveness Against Breakthrough Covid-19 Infectionsmentioning

confidence: 99%

“…Of the seventeen studies included in this review, sixteen have reported on hospitalisation of patients who received Tixagevimab/Cilgavimab. Six of these studies included corresponding controls 8,[16][17][18][19][20] . All of these studies demonstrated reduced rates of hospitalisation in patients receiving Tixagevimab/Cilgavimab.…”

Section: Clinical Effectiveness Against Covid-19 Hospitalisationmentioning

confidence: 99%

“…8,12,[16][17][18][19][20][22][23][24][25][27][28][29][30][31] (RRR: relative risk ratio; HR: hazard ratio; IRR: incidence risk ratio; OR: odds ratio; IQR: interquartile range)Neutralising ability of patient seraThis systematic review included 17 large scale human studies, including a total of 24,773 immunocompromised participants, of whom 10,775 received Tixagevimab/Cilgavimab as a prophylactic antibody therapy. While our findings are generally positive, it should be acknowledged that the real-world studies differed in quality.…”

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confidence: 99%

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Systematic review of the clinical effectiveness of Tixagevimab/Cilgavimab for prophylaxis of COVID-19 in immunocompromised patients

Suribhatla

Starkey

Ionescu³

et al. 2022

Preprint

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Background and aims Immunocompromised patients have a reduced ability to generate antibodies after COVID-19 vaccination and are at higher risk of SARS-CoV-2 infection, complications and mortality. Tixagevimab/Cilgavimab (Evusheld) is a monoclonal antibody combination which bind to the SARS-CoV-2 spike protein, preventing the virus entering human cells. The phase III PROVENT trial reported that immunocompromised patients given Tixagevimab/Cilgavimab had a significantly reduced risk of COVID-19 infection. However, PROVENT was conducted before the SARS-CoV-2 Omicron became prevalent. This systematic review provides an updated summary of real-world clinical evidence of Tixagevimab/Cilgavimab effectiveness in immunocompromised patients. Methods Two independent reviewers conducted PubMed and medRxiv searches for the period of 01/01/2021 to 01/10/2022. Clinical studies which reported the primary outcome of breakthrough COVID-19 infections after Tixagevimab/Cilgavimab administration were included in the review. COVID-19-related hospitalisations, ITU admissions and mortality were assessed as secondary outcomes. Clinical effectiveness was determined using the case-control clinical effectiveness methodology. The GRADE tool was used to ascertain the level of certainty for the primary outcome in each study. Results 17 clinical studies were included, comprising 24,773 immunocompromised participants of whom 10,775 received Tixagevimab/Cilgavimab. Most studies reported clinical outcomes during the SARS-CoV-2 Omicron wave. Six studies compared a Tixagevimab/Cilgavimab intervention group to a control group. Overall, the clinical effectiveness of prophylactic Tixagevimab/Cilgavimab against COVID-19 breakthrough infection, hospitalisation and ITU admission were 40.47%, 69.23% and 87.89%, respectively. For prevention of all-cause and COVID-19-specifc mortality, overall clinical effectiveness was 81.29% and 86.36%, respectively. Conclusions There is a growing body of real-world evidence validating the original PROVENT phase III study regarding the clinical effectiveness of Tixagevimab/Cilgavimab as prophylaxis for immunocompromised patients, notably demonstrating effectiveness during the Omicron wave. This review demonstrates the clinical effectiveness of prophylactic Tixagevimab/Cilgavimab at reducing COVID-19 infection, hospitalisation, ITU admission and mortality for immunosuppressed individuals. It is important that ongoing larger-scale and better-controlled real world studies are initiated and evaluated to provide ongoing certainty of the clinical benefit of prophylactic antibody treatment for immunocompromised patients in the face of new variants.

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Efficacy and safety of tixagevimab‐cilgavimab as pre‐exposure prophylaxis for COVID‐19: A systematic review and meta‐analysis

Soeroto

Yanto

Kurniawan

et al. 2023

Reviews in Medical Virology

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Some proportions of populations, such as immunocompromised patients and organ transplant recipients might have inadequate immune responses to the vaccine for coronavirus disease 2019 . For these groups of populations, administering monoclonal antibodies might offer some additional protection. This review sought to analyze the effectiveness and safety of tixagevimab-cilgavimab (Evusheld) as pre-exposure prophylaxis against COVID-19. We used specific keywords to comprehensively search for potential studies on PubMed, Scopus, Europe PMC, and ClinicalTrials.gov sources until 3 September 2022. We collected all published articles that analyzed tixagevimab-cilgavimab on the course of COVID-19. Review Manager 5.4 was utilized for statistical analysis. Six studies were included. Our pooled analysis revealed that tixagevimab-cilgavimab prophylaxis may decrease the rate of SARS-CoV-2 infection (OR: 0.24; 95% CI: 0.15-0.40, p < 0.00001, I 2 = 75%), lower COVID-19 hospitalization rate (OR: 0.13; 95% CI: 0.07-0.24, p < 0.00001, I 2 = 0%), decrease the severity risk (OR: 0.13; 95% CI: 0.07-0.24, p < 0.00001, I 2 = 0%), and lower COVID-19 deaths (OR: 0.17; 95% CI: 0.03-0.99, p = 0.05, I 2 = 72%). In the included studies, no major adverse events were reported. This study proposes that tixagevimab-cilgavimab was effective and safe for preventing COVID-19. Tixagevimab-cilgavimab may be offered to those who cannot be vaccinated or have inadequate immune response from the COVID-19 vaccine to give additional protection.

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Tixagevimab/Cilgavimab for Prevention of COVID-19 during the Omicron Surge: Retrospective Analysis of National VA Electronic Data

Cited by 20 publications

References 29 publications

Efficacy of COVID-19 Booster Vaccines in Patients with Hematologic Malignancies: Experiences in a Real-World Scenario

Efficacy of COVID-19 Booster Vaccines in Patients with Hematologic Malignancies: Experiences in a Real-World Scenario

Systematic review of the clinical effectiveness of Tixagevimab/Cilgavimab for prophylaxis of COVID-19 in immunocompromised patients

Efficacy and safety of tixagevimab‐cilgavimab as pre‐exposure prophylaxis for COVID‐19: A systematic review and meta‐analysis

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