Tixagevimab/cilgavimab pre-exposure prophylaxis is associated with lower breakthrough infection risk in vaccinated solid organ transplant recipients during the omicron wave
Ayman Al Jurdi, Leela Morena, Mariesa Cote, Emily Bethea, Jamil Azzi, Leonardo V Riella
American Journal of Transplantation, doi:10.1111/ajt.17128
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in solid organ transplant recipients (SOTRs) is associated with higher mortality compared to immunocompetent individuals. 1 Since antiviral responses to SARS-CoV-2 vaccines in SOTRs are attenuated, 2 additional strategies such as monoclonal antibody pre-exposure prophylaxis have been developed. 3 Tixagevimab and cilgavimab are neutralizing monoclonal antibodies directed against different epitopes of the receptor-binding domain of SARS-CoV-2 spike protein that have been associated with a lower risk of SARS-CoV-2 infection when used for pre-exposure prophylaxis in unvaccinated individuals. 4 Based on that, tixagevimab/cilgavimab received emergency use authorization from the US Food and Drug
| 3135 AJT AL JURDI et AL. We also found that tixagevimab/cilgavimab use was associated with a lower incidence of breakthrough infection regardless of whether SOTRs had received 0-3 or 4-5 vaccines doses. Separate analysis of SOTRs who received 0-2 or 5 vaccine doses was not performed due to the small number of SOTRs in these groups. In addition, we found that tixagevimab/cilgavimab use was associated with a lower risk of breakthrough infection in kidney and lung transplant recipients. There was no statistically significant difference in the risk of breakthrough infection between liver or liver/kidney transplant recipients who did and did not receive tixagevimab/cilgavimab. However, given the small number of liver and liver/kidney transplant recipients in our cohort, our study was underpowered to find differences in this subgroup of SOTRs. Importantly, we also found a higher incidence of breakthrough infections in the low-dose (150-150 mg) compared to the high-dose (300-300 mg) tixagevimab/cilgavimab cohort, suggesting a lower risk of breakthrough infections in the high-dose group, which supports the FDA's revised recommendation to use the higher dose for preexposure prophylaxis in SOTRs. 14 A randomized controlled trial comparing the two doses would provide further evidence supporting the difference in breakthrough infection between the two doses in SOTRs. We also found that tixagevimab/cilgavimab was safe with a low rate of adverse events and no evidence of allograft..
References
Altarawneh, Chemaitelly, Hasan, Protection against the omicron variant from previous SARS-CoV-2 infection, N Engl J Med,
doi:10.1056/NEJMc2200133Andrews, Stowe, Kirsebom, Covid-19 vaccine effectiveness against the omicron (B.1.1.529) variant, N Engl J Med,
doi:10.1056/NEJMoa2119451Bertrand, Laurent, Lemée, Efficacy of anti SARS-CoV-2 monoclonal antibodies prophylaxis and vaccination on omicron COVID-19 in kidney transplant recipients, Kidney Int,
doi:10.1016/j.kint.2022.05.007Caillard, Chavarot, Francois, Is COVID-19 infection more severe in kidney transplant recipients?, Am J Transplant,
doi:10.1111/ajt.16424Goldberg, Mandel, Bar-On, Protection and waning of natural and hybrid immunity to SARS-CoV-2, N Engl J Med,
doi:10.1056/NEJMoa2118946Hall, Foulkes, Charlett, SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN), Lancet,
doi:10.1016/S0140-6736(21)00675-9Hansen, Michlmayr, Gubbels, Mølbak, Ethelberg, Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study, Lancet,
doi:10.1016/S0140-6736(21)00575-4Jurdi, Gassen, Borges, Non-invasive monitoring for rejection in kidney transplant recipients after SARS-CoV-2 mRNA vaccination, Front Immunol,
doi:10.3389/fimmu.2022.838985Levin, Ustianowski, Wit, Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for prevention of Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2116620Loo, Mctamney, Arends, The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in nonhuman primates and has an extended half-life in humans, Sci Transl Med,
doi:10.1126/scitranslmed.abl8124Magen, Waxman, Makov-Assif, Fourth dose of BNT162b2 mRNA Covid-19 vaccine in a Nationwide setting, N Engl J Med,
doi:10.1056/NEJMoa2201688Sheehan, Reddy, Rothberg, Reinfection rates among patients who previously tested positive for coronavirus disease 2019: a retrospective cohort study, Clin Infect Dis,
doi:10.1093/cid/ciab234{ 'indexed': {'date-parts': [[2024, 1, 6]], 'date-time': '2024-01-06T22:57:33Z', 'timestamp': 1704581853900},
'reference-count': 15,
'publisher': 'Elsevier BV',
'issue': '12',
'license': [ { 'start': { 'date-parts': [[2022, 12, 1]],
'date-time': '2022-12-01T00:00:00Z',
'timestamp': 1669852800000},
'content-version': 'tdm',
'delay-in-days': 0,
'URL': 'https://www.elsevier.com/tdm/userlicense/1.0/'},
{ 'start': { 'date-parts': [[2023, 12, 1]],
'date-time': '2023-12-01T00:00:00Z',
'timestamp': 1701388800000},
'content-version': 'vor',
'delay-in-days': 365,
'URL': 'http://creativecommons.org/licenses/by-nc-nd/4.0/'}],
'funder': [ { 'DOI': '10.13039/100005294',
'name': 'Massachusetts General Hospital',
'doi-asserted-by': 'publisher',
'award': ['Harold and Ellen Danser Endowed/Distinguished Chai']}],
'content-domain': { 'domain': ['amjtransplant.org', 'elsevier.com', 'sciencedirect.com'],
'crossmark-restriction': True},
'published-print': {'date-parts': [[2022, 12]]},
'DOI': '10.1111/ajt.17128',
'type': 'journal-article',
'created': {'date-parts': [[2022, 6, 21]], 'date-time': '2022-06-21T18:18:34Z', 'timestamp': 1655835514000},
'page': '3130-3136',
'update-policy': 'http://dx.doi.org/10.1016/elsevier_cm_policy',
'source': 'Crossref',
'is-referenced-by-count': 70,
'title': 'Tixagevimab/cilgavimab pre-exposure prophylaxis is associated with lower breakthrough infection '
'risk in vaccinated solid organ transplant recipients during the omicron wave',
'prefix': '10.1016',
'volume': '22',
'author': [ { 'ORCID': 'http://orcid.org/0000-0002-7652-3399',
'authenticated-orcid': False,
'given': 'Ayman',
'family': 'Al Jurdi',
'sequence': 'first',
'affiliation': []},
{'given': 'Leela', 'family': 'Morena', 'sequence': 'additional', 'affiliation': []},
{'given': 'Mariesa', 'family': 'Cote', 'sequence': 'additional', 'affiliation': []},
{'given': 'Emily', 'family': 'Bethea', 'sequence': 'additional', 'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-6909-4645',
'authenticated-orcid': False,
'given': 'Jamil',
'family': 'Azzi',
'sequence': 'additional',
'affiliation': []},
{ 'ORCID': 'http://orcid.org/0000-0002-7636-3196',
'authenticated-orcid': False,
'given': 'Leonardo V.',
'family': 'Riella',
'sequence': 'additional',
'affiliation': []}],
'member': '78',
'reference': [ { 'issue': '3',
'key': '10.1111/ajt.17128_bib1',
'doi-asserted-by': 'crossref',
'first-page': '1295',
'DOI': '10.1111/ajt.16424',
'article-title': 'Is COVID-19 infection more severe in kidney transplant recipients?',
'volume': '21',
'author': 'Caillard',
'year': '2021',
'journal-title': 'Am J Transplant.'},
{ 'key': '10.1111/ajt.17128_bib2',
'doi-asserted-by': 'crossref',
'first-page': '838985',
'DOI': '10.3389/fimmu.2022.838985',
'article-title': 'Non-invasive monitoring for rejection in kidney transplant recipients '
'after SARS-CoV-2 mRNA vaccination',
'volume': '13',
'author': 'Al Jurdi',
'year': '2022',
'journal-title': 'Front Immunol.'},
{ 'issue': '635',
'key': '10.1111/ajt.17128_bib3',
'doi-asserted-by': 'crossref',
'first-page': 'eabl8124',
'DOI': '10.1126/scitranslmed.abl8124',
'article-title': 'The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective '
'in nonhuman primates and has an extended half-life in humans',
'volume': '14',
'author': 'Loo',
'year': '2022',
'journal-title': 'Sci Transl Med.'},
{ 'key': '10.1111/ajt.17128_bib4',
'doi-asserted-by': 'crossref',
'first-page': '2188',
'DOI': '10.1056/NEJMoa2116620',
'article-title': 'Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for prevention of '
'Covid-19',
'volume': '386',
'author': 'Levin',
'year': '2022',
'journal-title': 'N Engl J Med.'},
{ 'issue': '4',
'key': '10.1111/ajt.17128_bib5',
'doi-asserted-by': 'crossref',
'first-page': '384',
'DOI': '10.1001/jama.2021.24931',
'article-title': 'Tixagevimab and Cilgavimab (Evusheld) for pre-exposure prophylaxis of '
'COVID-19',
'volume': '327',
'year': '2022',
'journal-title': 'Jama.'},
{ 'issue': '17',
'key': '10.1111/ajt.17128_bib6',
'doi-asserted-by': 'crossref',
'first-page': '1603',
'DOI': '10.1056/NEJMoa2201688',
'article-title': 'Fourth dose of BNT162b2 mRNA Covid-19 vaccine in a Nationwide setting',
'volume': '386',
'author': 'Magen',
'year': '2022',
'journal-title': 'N Engl J Med.'},
{ 'issue': '16',
'key': '10.1111/ajt.17128_bib7',
'doi-asserted-by': 'crossref',
'first-page': '1532',
'DOI': '10.1056/NEJMoa2119451',
'article-title': 'Covid-19 vaccine effectiveness against the omicron (B.1.1.529) variant',
'volume': '386',
'author': 'Andrews',
'year': '2022',
'journal-title': 'N Engl J Med.'},
{ 'issue': '13',
'key': '10.1111/ajt.17128_bib8',
'doi-asserted-by': 'crossref',
'first-page': '1288',
'DOI': '10.1056/NEJMc2200133',
'article-title': 'Protection against the omicron variant from previous SARS-CoV-2 '
'infection',
'volume': '386',
'author': 'Altarawneh',
'year': '2022',
'journal-title': 'N Engl J Med.'},
{ 'key': '10.1111/ajt.17128_bib9',
'doi-asserted-by': 'crossref',
'first-page': '2201',
'DOI': '10.1056/NEJMoa2118946',
'article-title': 'Protection and waning of natural and hybrid immunity to SARS-CoV-2',
'volume': '25',
'author': 'Goldberg',
'year': '2022',
'journal-title': 'N Engl J Med.'},
{ 'issue': '10283',
'key': '10.1111/ajt.17128_bib10',
'doi-asserted-by': 'crossref',
'first-page': '1459',
'DOI': '10.1016/S0140-6736(21)00675-9',
'article-title': 'SARS-CoV-2 infection rates of antibody-positive compared with '
'antibody-negative health-care workers in England: a large, multicentre, '
'prospective cohort study (SIREN)',
'volume': '397',
'author': 'Hall',
'year': '2021',
'journal-title': 'Lancet (London, England).'},
{ 'issue': '10280',
'key': '10.1111/ajt.17128_bib11',
'doi-asserted-by': 'crossref',
'first-page': '1204',
'DOI': '10.1016/S0140-6736(21)00575-4',
'article-title': 'Assessment of protection against reinfection with SARS-CoV-2 among 4 '
'million PCR-tested individuals in Denmark in 2020: a population-level '
'observational study',
'volume': '397',
'author': 'Hansen',
'year': '2021',
'journal-title': 'Lancet (London, England).'},
{ 'issue': '10',
'key': '10.1111/ajt.17128_bib12',
'doi-asserted-by': 'crossref',
'first-page': '1882',
'DOI': '10.1093/cid/ciab234',
'article-title': 'Reinfection rates among patients who previously tested positive for '
'coronavirus disease 2019: a retrospective cohort study',
'volume': '73',
'author': 'Sheehan',
'year': '2021',
'journal-title': 'Clin Infect Dis.'},
{ 'key': '10.1111/ajt.17128_bib13',
'doi-asserted-by': 'crossref',
'article-title': 'Efficacy of anti SARS-CoV-2 monoclonal antibodies prophylaxis and '
'vaccination on omicron COVID-19 in kidney transplant recipients',
'author': 'Bertrand',
'year': '2022',
'journal-title': 'Kidney Int.',
'DOI': '10.1016/j.kint.2022.05.007'},
{ 'key': '10.1111/ajt.17128_bib14',
'unstructured': 'FDA. FDA authorizes revisions to Evusheld dosing. 2022. '
'https://www.fda.gov/drugs/drug-safety-and-availability/fda-authorizes-revisions-evusheld-dosing'},
{ 'key': '10.1111/ajt.17128_bib15',
'unstructured': 'CDC: Variant proportions. 2022. Accessed May 1, 2022. '
'https://covid.cdc.gov/covid-data-tracker/#variant-proportions'}],
'container-title': 'American Journal of Transplantation',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'https://onlinelibrary.wiley.com/doi/pdf/10.1111/ajt.17128',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://onlinelibrary.wiley.com/doi/full-xml/10.1111/ajt.17128',
'content-type': 'application/xml',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://api.elsevier.com/content/article/PII:S1600613523000655?httpAccept=text/xml',
'content-type': 'text/xml',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://api.elsevier.com/content/article/PII:S1600613523000655?httpAccept=text/plain',
'content-type': 'text/plain',
'content-version': 'vor',
'intended-application': 'text-mining'},
{ 'URL': 'https://onlinelibrary.wiley.com/doi/pdf/10.1111/ajt.17128',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2023, 12, 1]],
'date-time': '2023-12-01T12:55:33Z',
'timestamp': 1701435333000},
'score': 1,
'resource': {'primary': {'URL': 'https://linkinghub.elsevier.com/retrieve/pii/S1600613523000655'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2022, 12]]},
'references-count': 15,
'journal-issue': {'issue': '12', 'published-print': {'date-parts': [[2022, 12]]}},
'alternative-id': ['S1600613523000655'],
'URL': 'http://dx.doi.org/10.1111/ajt.17128',
'relation': {},
'ISSN': ['1600-6135'],
'subject': ['Pharmacology (medical)', 'Transplantation', 'Immunology and Allergy'],
'container-title-short': 'American Journal of Transplantation',
'published': {'date-parts': [[2022, 12]]},
'assertion': [ {'value': 'Elsevier', 'name': 'publisher', 'label': 'This article is maintained by'},
{ 'value': 'Tixagevimab/cilgavimab pre-exposure prophylaxis is associated with lower '
'breakthrough infection risk in vaccinated solid organ transplant recipients '
'during the omicron wave',
'name': 'articletitle',
'label': 'Article Title'},
{ 'value': 'American Journal of Transplantation',
'name': 'journaltitle',
'label': 'Journal Title'},
{ 'value': 'https://doi.org/10.1111/ajt.17128',
'name': 'articlelink',
'label': 'CrossRef DOI link to publisher maintained version'},
{'value': 'article', 'name': 'content_type', 'label': 'Content Type'},
{ 'value': 'Copyright © 2022 American Society of Transplantation & American Society of '
'Transplant Surgeons. Published by Elsevier Inc. All rights reserved. Published '
'by Elsevier B.V. All rights reserved.',
'name': 'copyright',
'label': 'Copyright'}]}
