COVID-19 morbidity decreases with tixagevimab–cilgavimab preexposure prophylaxis in kidney transplant recipient nonresponders or low-vaccine responders

Kaminski, Hannah; Gigan, Mickael; Vermorel, Agathe; Charrier, Manon; Guirle, Laura; Jambon, Frédéric; Lacapère, Arthur; Ménard, Coline; Moreau, Karine; Néau-Cransac, Martine; Novion, Marine; Pribat, Frederique; Taton, Benjamin; Borde, Sébastien; Burguet, Laure; Martinez, Charlie; Jasiek, M.; D’Halluin, Pauline; Lafon, Marie‐Edith; Merville, Pierre; Couzi, Lionel

doi:10.1016/j.kint.2022.07.008

Cited by 36 publications

(83 citation statements)

References 8 publications

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“…All our patients received the adjusted higher dose, either once or on two separate visits after the recommended dose modification by the FDA. While a recent in-vitro study showed reduced antibody neutralization of Tix-Cil against Omicron variants 13 , this did not have a significant clinical outcome in our study or similar studies during the Omicron variant period 9 , 14 , 15 .…”

Section: Discussioncontrasting

confidence: 74%

“…Such reduction in both COVID-19 related hospitalizations and deaths is significant. A similar report from a study of kidney transplant recipients (KTRs), has indicated that among patients who received Tix-Cil, only 1.2% were hospitalized as compared with 11.3% in the non-treated group 14 . They also reported one COVID-19 related death in the Tix-Cil group as compared to two deaths in the control group.…”

Section: Discussionmentioning

confidence: 82%

“…Additionally, our test positivity rate is similar to the Tix-Cil treated KTRs who were COVID-19 vaccine non-responders or low responders, following at least three doses of mRNA vaccines at the Bordeaux University Hospital in France. Among the 333 KTRs who received Tix-Cil, 12.3% developed symptomatic COVID-19 as compared to 43.3% of patients who did not receive Tix-Cil 14 . Other studies have also showed a significant reduction in the rates of SARS-CoV-2 positivity after Tix-Cil 1 , 17 .…”

Section: Discussionmentioning

confidence: 97%

See 2 more Smart Citations

The Prevention of COVID-19 in High-Risk Patients Using Tixagevimab–Cilgavimab (Evusheld): Real-World Experience at a Large Academic Center

Al-Obaidi

Gungor²,

Kurtin³

et al. 2023

The American Journal of Medicine

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Section: Discussioncontrasting

confidence: 74%

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

The Prevention of COVID-19 in High-Risk Patients Using Tixagevimab–Cilgavimab (Evusheld): Real-World Experience at a Large Academic Center

Al-Obaidi

Gungor²,

Kurtin³

et al. 2023

The American Journal of Medicine

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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%

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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“…Only the recently approved bebtelovimab retained its full neutralization capacity against all Omicron sub-lineages and the other VOCs, with Evusheld showing high levels of activity against all but BA.1.1. These data on the in vitro neutralization of Omicron variants by bebtelovimab and Evusheld, in combination with large clinical efficacy studies during waves dominated by other variants 32 and smaller retrospective studies 33 – 35 during Omicron waves, suggest that high doses of both treatments have an important role to play in treating and preventing infection with Omicron variants, although further clinical evidence is required to confirm this alongside the close monitoring of emergent resistance 36 .…”

Section: Sars-cov-2 Variant Evasion Of Mabsmentioning

confidence: 89%

SARS-CoV-2 variant evasion of monoclonal antibodies based on in vitro studies

Cox

Peacock²,

Harvey³

et al. 2022

Nat Rev Microbiol

212

142

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Monoclonal antibodies (mAbs) offer a treatment option for individuals with severe COVID-19 and are especially important in high-risk individuals where vaccination is not an option. Given the importance of understanding the evolution of resistance to mAbs by SARS-CoV-2, we reviewed the available in vitro neutralization data for mAbs against live variants and viral constructs containing spike mutations of interest. Unfortunately, evasion of mAb-induced protection is being reported with new SARS-CoV-2 variants. The magnitude of neutralization reduction varied greatly among mAb–variant pairs. For example, sotrovimab retained its neutralization capacity against Omicron BA.1 but showed reduced efficacy against BA.2, BA.4 and BA.5, and BA.2.12.1. At present, only bebtelovimab has been reported to retain its efficacy against all SARS-CoV-2 variants considered here. Resistance to mAb neutralization was dominated by the action of epitope single amino acid substitutions in the spike protein. Although not all observed epitope mutations result in increased mAb evasion, amino acid substitutions at non-epitope positions and combinations of mutations also contribute to evasion of neutralization. This Review highlights the implications for the rational design of viral genomic surveillance and factors to consider for the development of novel mAb therapies.

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COVID-19 morbidity decreases with tixagevimab–cilgavimab preexposure prophylaxis in kidney transplant recipient nonresponders or low-vaccine responders

Cited by 36 publications

References 8 publications

The Prevention of COVID-19 in High-Risk Patients Using Tixagevimab–Cilgavimab (Evusheld): Real-World Experience at a Large Academic Center

The Prevention of COVID-19 in High-Risk Patients Using Tixagevimab–Cilgavimab (Evusheld): Real-World Experience at a Large Academic Center

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

SARS-CoV-2 variant evasion of monoclonal antibodies based on in vitro studies

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