Tixagevimab/Cilgavimab in SARS-CoV-2 Prophylaxis and Therapy: A Comprehensive Review of Clinical Experience
Abstract
:1. Introduction
2. Methods
3. Tixagevimab/Cilgavimab
4. Prophylaxis
4.1. Clinical Trial Data
4.2. Real-World Evidence on Pre-Exposure Prophylaxis
5. Therapy
5.1. Clinical Trial Data
5.2. RWE on Therapy
6. Expert Opinion and Future Directions
7. Limitations
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Lineage | Tixagevimab/Cilgavimab | Sotrovimab (no Longer Recommended, According to NIH Living Guidance) | Casirivimab/ Imdevimab (no Longer Recommended, According to NIH Living Guidance) | Bebtelovimab (no Longer Recommended, According to NIH Living Guidance) | Bamlanivimab/ Etesevimab (no Longer Recommended, According to NIH Living Guidance) |
---|---|---|---|---|---|
Alpha | |||||
Beta | |||||
Gamma | |||||
Delta | |||||
Omicron | |||||
BA.1 | |||||
BA.1.1 | |||||
BA.2 | |||||
BA.2.12.1 | |||||
BA.2.75.2 | |||||
BA.4 | |||||
BA.4.6 | |||||
BA.5 | |||||
BQ.1/BQ1.1 | |||||
XBB (BA2.10.1 and BA.2.75 recombinant) |
Reference | Country of Origin | Population Characteristics | Outcomes |
---|---|---|---|
Pre-exposure prophylaxis | |||
Young-Xu, et al. Tixagevimab/Cilgavimab for Prevention of COVID-19 during the Omicron Surge: Retrospective Analysis of National VA Electronic Data. medRxiv 2022. [42] https://doi.org/10.1101/2022.05.28.22275716 (accessed on 10 December 2022) | USA |
| Composite endpoints: SARS-CoV-2 infection, COVID-19-related hospitalization, all-cause mortality Lower incidence of composite outcome 17/1733 (1.0%) vs 206/6354 (3.2%); HR 0.31; 95% CI, 0.18–0.53) lower SARS-CoV-2 infection (HR 0.34; 95% CI, 0.13–0.87) lower COVID-19 hospitalization (HR 0.13; 95% CI, 0.02–0.99) lower all-cause mortality (HR 0.36; 95% CI, 0.18–0.73) |
Ordaya EE, et al. Characterization of Early-Onse Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Immunocompromised Patients Who Received Tixagevimab-Cilgavimab Prophylaxis Open Forum Infect Dis. 2022. [48] https://doi.org/10.1093/ofid/ofac283 (accessed on 10 December 2022) | USA |
| Endpoint: SARS-CoV-2 infection, COVID-19-related hospitalization, all-cause mortality 8/674 (1.2%) infected with COVID-19 2/8 required hospitalization No deaths |
Kertes J et al. Association Between AZD7442 (Tixagevimab-Cilgavimab) Administration and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection, Hospitalization, and Mortality, Clinical Infectious Diseases, 2022; ciac625, [46] https://doi.org/10.1093/cid/ciac625 (accessed on 10 December 2022) | Israel |
| Endpoint: SARS-CoV-2 infection, COVID-19-related hospitalization, all-cause mortality 29/825 (3.5%) and 308/4299 (7.2%) infected with COVID-19 1/825(0.1%) compared with 27/4299(0.6%) hospitalized 0/825 compared with 40/4299(0.9%) mortality rate The AZD7442 group was half as likely to become infected with SARS-CoV-2 (OR: 0.51; 95% CI: 0.30–0.84) 92% less likely to be hospitalized/die than those not administered AZD7442 (OR: 0.08; 95% CI: 0.01–0.54). |
Stuver, R. et al. Activity of AZD7442 (tixagevimab-cilgavimab) against Omicron SARS-CoV-2 in patients with hematologic malignancies, Cancer Cell 2022, 40, 590–591. [23] https://doi.org/10.1016/j.ccell.2022.05.007 (accessed on 10 December 2022) | USA |
| Endpoint: anti-S IgG titers 47/47(100%) high titers neutralization of wild-type (WT) receptor-binding domain (RBD) 47/47 (100%) who received single dose 150 mg 5/5(100% who received additional 150 mg 5/5(100%) who received single dose of 300 mg neutralizing activity against Omicron-RBD (positive cut-off value = 30%) The median neutralization by subgroup of 47 was <30%; those who received 300 mg in total had a mean neutralization >30% (9/10 above 30%) differential neutralizing capacity against various Omicron sublineages; 300 mg dose of tixa/cilga for pre-exposure prophylaxis |
Benotmane, I. et al. Pre-exposure prophylaxis with Evusheld™elicits limited neutralizing activity against the Omicron variant in kidney transplant patients. medRxiv 2022. [59] https://doi.org/10.1101/2022.03.21.22272669 (accessed on 10 December 2022) | France |
| Primary endpoint: Omicron BA.1 neutralization activity after 29 days (median) 9.5% (6/63) of those who received Evusheld 71% (10/14) of those positive during the fifth wave 2.6% (1/39) of those who received casirivimab-imdevimab Secondary endpoint: anti-RBD IgG titers generally low after Evusheld injection high interindividual variability the patients’ body mass index has an inverse correlation with anti-RBD IgG titers no neutralizing activity with anti-RBD titers <2500 BAU/mL after Evusheld |
Bertrand, D. et al. Efficacy of anti–SARS-CoV-2 monoclonal antibody prophylaxis and vaccination on the Omicron variant of COVID-19 in kidney transplant recipients. Letter. Kidney Int. 2022. [58] https://doi.org/10.1016/j.kint.2022.05.007(accessed on 10 December 2022) | France |
| Endpoint: Incidence of Omicron SARS-CoV-2 infection, COVID-19-related hospitalization, all-cause mortality 113/860(13.1%) infected with COVID-19 21/860(2%) required hospitalization (8 in the ICU) 5/860 (0.6%) COVID-19-related deaths The occurrence of infection, symptomatic infection, hospitalization, intensive care unit hospitalization, and COVID-19 death were significantly increased in patients in group 3 Patients in groups 1 and 2 showed similar results |
Kaminski, H. et al. COVID-19 morbidity decreases with tixagevimab–cilgavimab preexposure prophylaxis in kidney transplant recipient nonresponders or low-vaccine responders. Letter in press. Kidney Int. 2022. [52] https://doi.org/10.1016/j.kint.2022.07.008 (accessed on 10 December 2022) | France |
| Endpoint: Incidence of Omicron SARS-CoV-2 infection, COVID-19-related hospitalization, all-cause mortality 41/333 (12.3%) and 42/97 (43.3%) infected with COVID-19 4/333 (1.2%) and 11/97 (11.3%) required hospitalization (2 and 6 KTR respectively required in the ICU) 1/333 (0.3%) and 2/97 (2%) COVID-19-related deaths preexposure prophylaxis with tixagevimab–cilgavimab is effective onCOVID-19 infection caused by Omicron in KTRs |
Al Jurdi et al. Tixagevimab/cilgavimab pre-exposure prophylaxis is associated with lower breakthrough infection risk in vaccinated solid organ transplant recipients during the Omicron wave. Online ahead of print. Am. J Transplant. 2022. [43] https://doi.org/10.1111/ajt.17128 (accessed on 10 December 2022) | USA |
| Endpoint: Incidence of breakthrough COVID-19 infection Breakthrough infection in 11 (5%) from group 1 and 32 (14%) from group 2 150–150 mg dose subgroup had a higher incidence of breakthrough infections compared to those who received the 300–300 mg dose |
Karaba et al. Omicron BA.1 and BA.2 Neutralizing Activity following Pre-Exposure Prophylaxis with Tixagevimab plus Cilgavimab inVaccinated Solid Organ Transplant Recipients. medRxiv 2022. [45] https://doi.org/10.1101/2022.05.24.22275467 (accessed on 10 December 2022) | USA |
| Endpoints: Neutralization of SARS-CoV-2 variants after tixa/cilga (achieving ≥20% ACE2 inhibition) Omicron BA.1: from 5/61 (8%) to 10/61 (16%) (p-value:0.06) Omicron BA.2: from 4/61 (7%) to 44/61 (72%) (p-value < 0.001) The change in titer was similar for those receiving a single 300 + 300 mg dose, versus two 150 + 150 mg doses. |
Conte, W.L. et al. Tixagevimab and Cilgavimab (Evusheld) boost antibody levels to SARS-CoV-2 in patients with multiple sclerosis on b-cell depleters. Mult Scler Relat Disord. 2022. [49] https://doi.org/10.1016/j.msard.2022.103905(accessed on 10 December 2022) | USA |
| Endpoints: Level of SARS-CoV-2 antibody response At baseline 12/18 were lower than 0.8 U/mL and 6/18 were above threshold Two weeks after tixa/cilga 100% had an antibody response above threshold (>250 U/mL; p-value < 0.001) |
Ocon, A.J. et al. Real-World experience of Tixagevimab and Cilgavimab (Evusheld) in rheumatologic patients on Rituximab [50] https://doi.org/10.1097/rhu.0000000000001907 (accessed on 10 December 2022) | USA |
| Endpoint: Infection with SARS-CoV-2 after 100 ± 33 days 1/43 experienced symptomatic infection No serious adverse events occurred |
Calabrese, C. et al. Early experience with tixagevimab/cilgavimab pre-exposure prophylaxis in patients with immune-mediated inflammatory disease undergoing B cell depleting therapy and those with inborn errors of humoral immunity. Letter and supplementary data. RMD Open. 2022;8(2):e002557 [44] http://dx.doi.org/10.1136/rmdopen-2022-002557 (accessed on 10 December 2022) | USA |
| Endpoints: SARS-CoV-2 infection, COVID-19-related hospitalization, mortality 12/412 (2.91%) developed breakthrough COVID-19 6 were from group 1 and 6 from group 2 Group 1 patients developedinfection a median of 19 days (13–84) Group 2 patients developed infection a median of 38.5 days (19–72) One patient required hospitalization and high-flow oxygen There were no deaths |
Chen, B. et al. Real-World Effectiveness of Tixagevimab/cilgavimab (Evusheld) in the Omicron Era. Pre-print. medRxiv. 2022 [57] https://doi.org/10.1101/2022.09.16.22280034 (accessed on 10 December 2022) | USA |
| Endpoints: SARS-CoV-2 infection, COVID-19-related hospitalization, mortality SARS-CoV-2 infection: 121/1295 (9.3%) before and 102/1295 (7.9%) after receiving tixa/cilga Hospitalization: 36/121 (29.8%) (8/36 required ICU) and 6/102 (5.9%) No COVID-19-related deaths occurred |
Nguyen, Y. et al. Pre-exposure prophylaxis with tixagevimab and cilgavimab (Evusheld) for COVID-19 among 1112 severely immunocompromised patients. Research note in press. Clin Microbiol Infect. 2022. [47] https://doi.org/10.1016/j.cmi.2022.07.015 (accessed on 10 December 2022) | France |
| Endpoints: SARS-CoV-2 infection, severity of illness, mortality after median 63 (49–73) days SARS-CoV-2 infection: 49/1112 (4.4%) ≥ 5 days after treatment Mild to moderate illness: 43/49 (88%) Moderate-to-severe illness:6/49 (12%) Deaths:2/49 (4%) |
Benotmane, I. et al. Breakthrough COVID-19 cases despite prophylaxis with 150 mg of tixagevimab and 150 mg of cilgavimab in kidney transplant recipients. [60] https://doi.org/10.1111/ajt.17121 (accessed on 10 December 2022) | France |
| Endpoints: SARS-CoV-2 infection, COVID-19-related hospitalization, mortality SARS-CoV-2 infection: 39/419 (9.4%) Hospitalization:14/39 (35.9%) (3 patients were admitted to the ICU) Deaths: 2/39 (5.1%) Pre-exposure prophylaxis with Evusheld™ does not adequately protect KTRs against Omicron |
Al-Obaidi, M.M., Gungor A.B., Kurtin S.E., Mathias A.E., Tanriover B., and Zangeneh, T.T. The Prevention of COVID-19 in High-Risk Patients Using Tixagevimab-Cilgavimab (Evusheld): Real-World Experience at a Large Academic Center. Am J Med. 2022. [53] https://doi.org/10.1016/j.amjmed.2022.08.019 (accessed on 10 December 2022) | USA |
| Endpoints: SARS-CoV-2 infection, COVID-19-related hospitalization, mortality SARS-CoV-2 infection: 6/98 (who had PCR test available) Hospitalization: 42/463 (9.1%) Deaths: 4/463(0.9%). no deaths were attributed to COVID-19 |
Davis, J.A., Granger, K., Roubal, K., Smith, D., Gaffney, K.J., McGann, M. et al. Efficacy of tixagevimab-cilgavimab in preventing SARS-CoV-2 for patients with B-cell malignancies. Blood. 2022 [54] https://doi.org/10.1182/blood.2022018283 (accessed on 10 December 2022) | USA |
| Endpoints: incidence of COVID-19 breakthrough infections COVID-19-related hospitalization, mortality Breakthrough cases at median 91-day follow-up: 27/251 (10.7%) Hospitalization: 4/27 (15%) No deaths observed |
Najjar-Debbiny, R., Gronich, N., Weber, G., Stein, N., Saliba, W. Effectiveness of Evusheld in Immunocompromised Patients: Propensity Score-Matched Analysis. Clin Infect. Dis. 2022 [55] https://doi.org/10.1093/cid/ciac855 (accessed on 10 December 2022) | Israel |
| Endpoints: SARS-CoV-2 infection, COVID-19-related hospitalization SARS-CoV-2 infection: 72/703 (10.2%) and 377/2812 (13.4%); HR 0.75 (95% CI, 0.58–0.96); p-value: 0.023 Hospitalization: 7/72 and 67/377; HR 0.41 (0.19–0.89); p-value: 0.025 |
Zerbit, J. et al. Patients with Hematological Malignancies Treated with T-Cell or B-Cell Immunotherapy Remain at High Risk of Severe Forms of COVID-19 in the Omicron Era. Viruses 2022, 14, 2377. [56] https://doi.org/10.3390/v14112377 (accessed on 10 December 2022) | France |
| Endpoints: SARS-CoV-2 infection, COVID-19-related hospitalization, mortality SARS-CoV-2 infection: 57/338 (16.9%) Hospitalization: 13/57 (22.8%), of whom 11/13 (84.6%) required invasive mechanical ventilation 3 deaths were recorded |
Jondreville L.; et al. Pre-exposure prophylaxis with tixagevimab/cilgavimab (AZD7442) prevents severe SARS-CoV-2 infection in recipients of allogeneic hematopoietic stem cell transplantation during the Omicron wave: a multicentric retrospective study of SFGM-TC. J Hematol Oncol. 2022 Nov 28;15(1):169 [61] https://doi.org/10.1186/s13045-022-01387-0 (accessed on 10 December 2022) | France |
| Endpoints: SARS-CoV-2 infection, COVID-19-related hospitalization, mortality 139/161 (86.3%) remained uninfected 22/161(13.7%) symptomatic SARS-CoV 2 infection 8/22 (36.4%) received an additional treatment No hospitalizations recorded No deaths recorded |
Aqeel, F., and Geetha, D. (2022). Tixagevimab and Cilgavimab (Evusheld) in Rituximab-treated Antineutrophil Cytoplasmic Antibody Vasculitis Patients. Kidney International Reports, 7(11), 2537–2538. [63] https://doi.org/10.1016/j.ekir.2022.08.019 (accessed on 10 December 2022) | USA |
| Primary Endpoints: SARS-CoV-2 infection, COVID-19-related hospitalization, mortality The one patient who received the lower Evusheld dose was infected with SARS-CoV-2 122 days after receiving Evusheld 3/20 (15%) developed breakthrough COVID-19 disease No hospitalizations recorded No deaths recorded |
Woopen, C., Konofalska, U., Akgün, K., and Ziemssen, T. (2022). Case report: Variant-specific pre-exposure prophylaxis of SARS-CoV-2 infection in multiple sclerosis patients lacking vaccination responses (Case Report). Frontiers in Immunology, 13. [64] https://doi.org/10.3389/fimmu.2022.897748 (accessed on 10 December 2022) | Germany |
| Endpoints: SARS-CoV-2 infection, COVID-19-related hospitalization, mortality 1/6 asymptomatic SARS-CoV-2 infection before Tixa/Cilga No hospitalizations recorded No deaths recorded |
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Akinosoglou, K.; Rigopoulos, E.-A.; Kaiafa, G.; Daios, S.; Karlafti, E.; Ztriva, E.; Polychronopoulos, G.; Gogos, C.; Savopoulos, C. Tixagevimab/Cilgavimab in SARS-CoV-2 Prophylaxis and Therapy: A Comprehensive Review of Clinical Experience. Viruses 2023, 15, 118. https://doi.org/10.3390/v15010118
Akinosoglou K, Rigopoulos E-A, Kaiafa G, Daios S, Karlafti E, Ztriva E, Polychronopoulos G, Gogos C, Savopoulos C. Tixagevimab/Cilgavimab in SARS-CoV-2 Prophylaxis and Therapy: A Comprehensive Review of Clinical Experience. Viruses. 2023; 15(1):118. https://doi.org/10.3390/v15010118
Chicago/Turabian StyleAkinosoglou, Karolina, Emmanouil-Angelos Rigopoulos, Georgia Kaiafa, Stylianos Daios, Eleni Karlafti, Eleftheria Ztriva, Georgios Polychronopoulos, Charalambos Gogos, and Christos Savopoulos. 2023. "Tixagevimab/Cilgavimab in SARS-CoV-2 Prophylaxis and Therapy: A Comprehensive Review of Clinical Experience" Viruses 15, no. 1: 118. https://doi.org/10.3390/v15010118
APA StyleAkinosoglou, K., Rigopoulos, E.-A., Kaiafa, G., Daios, S., Karlafti, E., Ztriva, E., Polychronopoulos, G., Gogos, C., & Savopoulos, C. (2023). Tixagevimab/Cilgavimab in SARS-CoV-2 Prophylaxis and Therapy: A Comprehensive Review of Clinical Experience. Viruses, 15(1), 118. https://doi.org/10.3390/v15010118