Effectiveness of regdanvimab treatment for SARS-CoV-2 delta variant, which exhibited decreased in vitro activity: a nationwide real-world multicenter cohort study

{ 'indexed': {'date-parts': [[2023, 5, 16]], 'date-time': '2023-05-16T04:42:19Z', 'timestamp': 1684212139788}, 'reference-count': 37, 'publisher': 'Frontiers Media SA', 'license': [ { 'start': { 'date-parts': [[2023, 5, 15]], 'date-time': '2023-05-15T00:00:00Z', 'timestamp': 1684108800000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'funder': [ { 'DOI': '10.13039/100018688', 'name': 'Korea Disease Control and Prevention Agency', 'doi-asserted-by': 'publisher', 'award': ['#2021-ER1907-00']}], 'content-domain': {'domain': ['frontiersin.org'], 'crossmark-restriction': True}, 'abstract': '<jats:sec><jats:title>Background</jats:title><jats:p>Immune-evading severe acute respiratory ' 'syndrome coronavirus 2 (SARS-CoV-2) variants are emerging continuously. The clinical ' 'effectiveness of monoclonal antibody agents that exhibit decreased <jats:italic>in ' 'vitro</jats:italic> activity against SARS-CoV-2 variants needs to be ' 'elucidated.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A ' 'nationwide, multicenter, retrospective cohort study was designed to evaluate the ' 'effectiveness of regdanvimab, an anti-SARS-CoV-2 monoclonal antibody agent. Regdanvimab was ' 'prescribed in South Korea before and after the emergence of the delta variant, against which ' 'the <jats:italic>in vitro</jats:italic> activity of regdanvimab was decreased but present. ' 'Mild to moderate coronavirus 2019 (COVID-19) patients with risk factors for disease ' 'progression who were admitted within seven days of symptom onset were screened in four ' 'designated hospitals between December 2020 and September 2021. The primary outcomes, ' 'O<jats:sub>2</jats:sub> requirements and progression to severe disease within 21 days of ' 'admission, were compared between the regdanvimab and supportive care groups, with a subgroup ' 'analysis of delta variant–confirmed ' 'patients.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of ' '2,214 mild to moderate COVID-19 patients were included, of whom 1,095 (49.5%) received ' 'regdanvimab treatment. In the analysis of the total cohort, significantly fewer patients in ' 'the regdanvimab group than the supportive care group required O<jats:sub>2</jats:sub> support ' '(18.4% vs. 27.1%, <jats:italic>P</jats:italic> &amp;lt; 0.001) and progressed to severe ' 'disease (4.0% vs. 8.0%, <jats:italic>P</jats:italic> &amp;lt; 0.001). In the multivariable ' 'analysis, regdanvimab was significantly associated with a decreased risk for ' 'O<jats:sub>2</jats:sub> support (HR 0.677, 95% CI 0.561–0.816) and progression to severe ' 'disease (HR 0.489, 95% CI 0.337–0.709). Among the 939 delta-confirmed patients, ' 'O<jats:sub>2</jats:sub> support (21.5% vs. 23.5%, <jats:italic>P</jats:italic> = 0.526) and ' 'progression to severe disease (4.2% vs. 7.3%, <jats:italic>P</jats:italic> = 0.055) did not ' 'differ significantly between the regdanvimab and supportive care groups. In the multivariable ' 'analyses, regdanvimab treatment was not significantly associated with a decreased risk for ' 'O<jats:sub>2</jats:sub> support (HR 0.963, 95% CI 0.697–1.329) or progression to severe ' 'disease (HR 0.665, 95% CI 0.349–1.268) in delta-confirmed ' 'group.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Regdanvimab ' 'treatment effectively reduced progression to severe disease in the overall study population, ' 'but did not show significant effectiveness in the delta-confirmed patients. The effectiveness ' 'of dose increment of monoclonal antibody agents should be evaluated for variant strains ' 'exhibiting reduced susceptibility.</jats:p></jats:sec>', 'DOI': '10.3389/fcimb.2023.1192512', 'type': 'journal-article', 'created': {'date-parts': [[2023, 5, 15]], 'date-time': '2023-05-15T13:30:25Z', 'timestamp': 1684157425000}, 'update-policy': 'http://dx.doi.org/10.3389/crossmark-policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Effectiveness of regdanvimab treatment for SARS-CoV-2 delta variant, which exhibited decreased ' 'in vitro activity: a nationwide real-world multicenter cohort study', 'prefix': '10.3389', 'volume': '13', 'author': [ {'given': 'Haein', 'family': 'Kim', 'sequence': 'first', 'affiliation': []}, {'given': 'Young Rock', 'family': 'Jang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ji Yeon', 'family': 'Lee', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jae-Hoon', 'family': 'Ko', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jee Young', 'family': 'Lee', 'sequence': 'additional', 'affiliation': []}, {'given': 'Seongcheol', 'family': 'Cho', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yong Dae', 'family': 'Lee', 'sequence': 'additional', 'affiliation': []}, {'given': 'Junghoon', 'family': 'Song', 'sequence': 'additional', 'affiliation': []}, {'given': 'Miri', 'family': 'Hyun', 'sequence': 'additional', 'affiliation': []}, {'given': 'Hyun Ah', 'family': 'Kim', 'sequence': 'additional', 'affiliation': []}, {'given': 'Soyoon', 'family': 'Hwang', 'sequence': 'additional', 'affiliation': []}, {'given': 'Sangmi', 'family': 'Ryou', 'sequence': 'additional', 'affiliation': []}, {'given': 'Yoo Jin', 'family': 'Na', 'sequence': 'additional', 'affiliation': []}, {'given': 'Joo-Yeon', 'family': 'Lee', 'sequence': 'additional', 'affiliation': []}, {'given': 'Changhee', 'family': 'Lee', 'sequence': 'additional', 'affiliation': []}, {'given': 'Nan Young', 'family': 'Lee', 'sequence': 'additional', 'affiliation': []}, {'given': 'Seunghwan', 'family': 'Shin', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ki Tae', 'family': 'Kwon', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jin Yong', 'family': 'Kim', 'sequence': 'additional', 'affiliation': []}, {'given': 'Kyong Ran', 'family': 'Peck', 'sequence': 'additional', 'affiliation': []}], 'member': '1965', 'published-online': {'date-parts': [[2023, 5, 15]]}, 'reference': [ { 'key': 'B1', 'doi-asserted-by': 'publisher', 'first-page': '1390.e1', 'DOI': '10.1016/j.cmi.2022.04.019', 'article-title': 'Heterologous ChAdOx1 and Bnt162b2 vaccination induces strong ' 'neutralizing antibody responses against SARS-CoV-2 including delta ' 'variant with tolerable reactogenicity', 'volume': '28', 'author': 'Bae', 'year': '2022', 'journal-title': 'Clin. Microbiol. Infect.'}, { 'key': 'B2', 'doi-asserted-by': 'publisher', 'first-page': '105026', 'DOI': '10.1016/j.jcv.2021.105026', 'article-title': 'Breakthrough COVID-19 and casirivimab-imdevimab treatment during a ' 'SARS-CoV-2 B1', 'volume': '145', 'author': 'Bierle', 'year': '2021', 'journal-title': '617.2 (Delta) surge. J. Clin. Virol.'}, { 'key': 'B3', 'doi-asserted-by': 'publisher', 'first-page': '112', 'DOI': '10.1038/s41579-022-00809-7', 'article-title': 'SARS-CoV-2 variant evasion of monoclonal antibodies based on in vitro ' 'studies', 'volume': '21', 'author': 'Cox', 'year': '2023', 'journal-title': 'Nat. Rev. Microbiol.'}, { 'key': 'B4', 'doi-asserted-by': 'publisher', 'first-page': '1382', 'DOI': '10.1056/NEJMoa2102685', 'article-title': 'Bamlanivimab plus etesevimab in mild or moderate covid-19', 'volume': '385', 'author': 'Dougan', 'year': '2021', 'journal-title': 'N. Engl. J. Med.'}, { 'key': 'B5', 'doi-asserted-by': 'publisher', 'first-page': '632', 'DOI': '10.1001/jama.2021.0202', 'article-title': 'Effect of bamlanivimab as monotherapy or in combination with etesevimab ' 'on viral load in patients with mild to moderate COVID-19: a randomized ' 'clinical trial', 'volume': '325', 'author': 'Gottlieb', 'year': '2021', 'journal-title': 'Jama'}, { 'key': 'B6', 'doi-asserted-by': 'publisher', 'first-page': '1236', 'DOI': '10.1001/jama.2022.2832', 'article-title': 'Effect of sotrovimab on hospitalization or death among high-risk ' 'patients with mild to moderate COVID-19: a randomized clinical trial', 'volume': '327', 'author': 'Gupta', 'year': '2022', 'journal-title': 'Jama'}, { 'key': 'B7', 'unstructured': 'Il-Hwan KimA. K. P.\n' ' LeeH.\n' ' KimJ.\n' ' KimD. H.\n' ' KimJ.\n' ' NoJ. S.\n' ' COVID-19 special report] July 2021 status and characteristics ' 'of the COVID-19 variant virus outbreak in the republic of Korea2021'}, { 'key': 'B8', 'doi-asserted-by': 'publisher', 'first-page': '94', 'DOI': '10.1016/j.ijid.2022.12.035', 'article-title': 'Regdanvimab for patients with mild-to-moderate COVID-19: a ' 'retrospective cohort study and subgroup analysis of patients with the ' 'delta variant', 'volume': '130', 'author': 'Jang', 'year': '2023', 'journal-title': 'Int. J. Infect. Dis.'}, { 'key': 'B9', 'doi-asserted-by': 'publisher', 'DOI': '10.3346/jkms.2021.36.e83', 'article-title': 'Clinical and virologic effectiveness of remdesivir treatment for severe ' 'coronavirus disease 2019 (COVID-19) in Korea: a nationwide multicenter ' 'retrospective cohort study', 'volume': '36', 'author': 'Joo', 'year': '2021', 'journal-title': 'J. Korean Med. Sci.'}, {'key': 'B10', 'unstructured': 'Weakly briefing of COVID-19 and vaccination status2021'}, { 'key': 'B11', 'unstructured': 'COVID-19 special report] outbreak report of COVID-19 during designation ' 'of class 1 infectious disease in the republic of Korea (January 20, ' '2020–April 24, 2022)2022'}, { 'key': 'B12', 'unstructured': 'COVID-19 special report] epidemiological characteristics of COVID-19 ' 'reinfection cases in the republic of Korea2022'}, { 'key': 'B13', 'doi-asserted-by': 'publisher', 'first-page': '288', 'DOI': '10.1038/s41467-020-20602-5', 'article-title': 'A therapeutic neutralizing antibody targeting receptor binding domain ' 'of SARS-CoV-2 spike protein', 'volume': '12', 'author': 'Kim', 'year': '2021', 'journal-title': 'Nat. Commun.'}, { 'key': 'B14', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fimmu.2021.772320', 'article-title': 'Effectiveness of regdanvimab treatment in high-risk COVID-19 patients ' 'to prevent progression to severe disease', 'volume': '12', 'author': 'Lee', 'year': '2021', 'journal-title': 'Front. Immunol.'}, { 'key': 'B15', 'doi-asserted-by': 'publisher', 'first-page': '108570', 'DOI': '10.1016/j.intimp.2022.108570', 'article-title': 'Regdanvimab in patients with mild-to-moderate SARS-CoV-2 infection: a ' 'propensity score-matched retrospective cohort study', 'volume': '106', 'author': 'Lee', 'year': '2022', 'journal-title': 'Int. Immunopharmacol.'}, { 'key': 'B16', 'doi-asserted-by': 'publisher', 'first-page': '258', 'DOI': '10.3947/ic.2022.0011', 'article-title': 'Early oxygen requirement in patients with mild-to-Moderate COVID-19 who ' 'received regdanvimab after delta-variant outbreak', 'volume': '54', 'author': 'Lee', 'year': '2022', 'journal-title': 'Infect. Chemother.'}, { 'key': 'B17', 'first-page': '152', 'article-title': 'SA. "Error statistics"', 'volume-title': 'Philosophy of statistics', 'author': 'Mayo', 'year': '2010'}, { 'key': 'B18', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fimmu.2022.968105', 'article-title': 'Kinetics of vaccine-induced neutralizing antibody titers and estimated ' 'protective immunity against wild-type SARS-CoV-2 and the delta variant: ' 'a prospective nationwide cohort study comparing three COVID-19 ' 'vaccination protocols in south Korea', 'volume': '13', 'author': 'Nham', 'year': '2022', 'journal-title': 'Front. Immunol.'}, { 'key': 'B19', 'doi-asserted-by': 'publisher', 'DOI': '10.3346/jkms.2022.37.e351', 'article-title': 'COVID-19 vaccination in Korea: past, present, and the way forward', 'volume': '37', 'author': 'Nham', 'year': '2022', 'journal-title': 'J. Korean Med. Sci.'}, { 'key': 'B20', 'unstructured': 'COVID-19 treatment guidelines, anti-SARS-CoV-2 monoclonal antibodies'}, { 'key': 'B21', 'doi-asserted-by': 'publisher', 'first-page': 'e27', 'DOI': '10.1093/cid/ciac239', 'article-title': 'Clinical and virological characteristics of severe acute respiratory ' 'syndrome coronavirus 2 (SARS-CoV-2) B.1.617.2 (Delta) variant: a ' 'prospective cohort study', 'volume': '75', 'author': 'Park', 'year': '2022', 'journal-title': 'Clin. Infect. Dis.'}, { 'key': 'B22', 'doi-asserted-by': 'publisher', 'first-page': '276', 'DOI': '10.1038/s41586-021-03777-9', 'article-title': 'Reduced sensitivity of SARS-CoV-2 variant delta to antibody ' 'neutralization', 'volume': '596', 'author': 'Planas', 'year': '2021', 'journal-title': 'Nature'}, { 'key': 'B23', 'doi-asserted-by': 'publisher', 'first-page': '91', 'DOI': '10.1016/j.bbrc.2021.09.023', 'article-title': 'The in vitro and in vivo efficacy of CT-P59 against gamma, delta and ' 'its associated variants of SARS-CoV-2', 'volume': '578', 'author': 'Ryu', 'year': '2021', 'journal-title': 'Biochem. Biophys. Res. Commun.'}, { 'key': 'B24', 'doi-asserted-by': 'publisher', 'first-page': '7425', 'DOI': '10.3390/ijms22147425', 'article-title': 'Structural evaluation of the spike glycoprotein variants on SARS-CoV-2 ' 'transmission and immune evasion', 'volume': '22', 'author': 'Salleh', 'year': '2021', 'journal-title': 'Int. J. Mol. Sci.'}, { 'key': 'B25', 'doi-asserted-by': 'publisher', 'first-page': 'ofac053', 'DOI': '10.1093/ofid/ofac053', 'article-title': 'Efficacy and safety of regdanvimab (CT-P59): a phase 2/3 randomized, ' 'double-blind, placebo-controlled trial in outpatients with ' 'mild-to-Moderate coronavirus disease 2019', 'volume': '9', 'author': 'Streinu-Cercel', 'year': '2022', 'journal-title': 'Open Forum Infect. Dis.'}, { 'key': 'B26', 'doi-asserted-by': 'publisher', 'DOI': '10.3346/jkms.2020.35.e280', 'article-title': 'Clinical course and outcomes of 3,060 patients with coronavirus disease ' '2019 in Korea, January-may 2020', 'volume': '35', 'author': 'Sung', 'year': '2020', 'journal-title': 'J. Korean Med. Sci.'}, { 'key': 'B27', 'doi-asserted-by': 'publisher', 'first-page': '2133', 'DOI': '10.1007/s40265-021-01626-7', 'article-title': 'Regdanvimab: first approval', 'volume': '81', 'author': 'Syed', 'year': '2021', 'journal-title': 'Drugs'}, { 'key': 'B28', 'doi-asserted-by': 'publisher', 'first-page': '1475', 'DOI': '10.1056/NEJMc2201933', 'article-title': 'Efficacy of antiviral agents against the SARS-CoV-2 omicron subvariant ' 'BA', 'volume': '386', 'author': 'Takashita', 'year': '2022', 'journal-title': '2. N. Engl. J. Med.'}, { 'key': 'B29', 'doi-asserted-by': 'publisher', 'first-page': '35', 'DOI': '10.1016/S1473-3099(21)00475-8', 'article-title': 'Hospital admission and emergency care attendance risk for SARS-CoV-2 ' 'delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a ' 'cohort study', 'volume': '22', 'author': 'Twohig', 'year': '2022', 'journal-title': 'Lancet Infect. Dis.'}, { 'key': 'B30', 'doi-asserted-by': 'publisher', 'first-page': '490', 'DOI': '10.1038/s41591-021-01678-y', 'article-title': 'An infectious SARS-CoV-2 B.1.1.529 omicron virus escapes neutralization ' 'by therapeutic monoclonal antibodies', 'volume': '28', 'author': 'VanBlargan', 'year': '2022', 'journal-title': 'Nat. Med.'}, { 'key': 'B31', 'doi-asserted-by': 'publisher', 'first-page': '1', 'DOI': '10.1056/NEJMoa2035002', 'article-title': 'REGEN-COV antibody combination and outcomes in outpatients with ' 'covid-19', 'volume': '385', 'author': 'Weinreich', 'year': '2021', 'journal-title': 'N. Engl. J. Med.'}, { 'key': 'B32', 'doi-asserted-by': 'publisher', 'first-page': '2031', 'DOI': '10.2146/ajhp040558', 'article-title': 'Number needed to treat: a descriptor for weighing therapeutic options', 'volume': '62', 'author': 'Wen', 'year': '2005', 'journal-title': 'Am. J. Health Syst. Pharm.'}, {'key': 'B33', 'unstructured': 'WHO coronavirus (COVID-19) dashboard'}, {'key': 'B34', 'unstructured': 'Tracking SARS-CoV-2 variants'}, { 'key': 'B35', 'doi-asserted-by': 'publisher', 'first-page': '942', 'DOI': '10.1016/S1473-3099(22)00365-6', 'article-title': 'Neutralisation sensitivity of SARS-CoV-2 omicron subvariants to ' 'therapeutic monoclonal antibodies', 'volume': '22', 'author': 'Yamasoba', 'year': '2022', 'journal-title': 'Lancet Infect. Dis.'}, { 'key': 'B36', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fimmu.2023.1139980', 'article-title': 'Neutralizing activity against omicron BA.5 after tixagevimab/cilgavimab ' 'administration comparable to those after omicron BA.1/BA.2 breakthrough ' 'infections', 'volume': '14', 'author': 'Yang', 'year': '2023', 'journal-title': 'Front. Immunol.'}, { 'key': 'B37', 'doi-asserted-by': 'publisher', 'DOI': '10.1126/science.abn8897', 'article-title': 'Structural basis for potent antibody neutralization of SARS-CoV-2 ' 'variants including B.1.1.529', 'volume': '376', 'author': 'Zhou', 'year': '2022', 'journal-title': 'Science'}], 'container-title': 'Frontiers in Cellular and Infection Microbiology', 'original-title': [], 'link': [ { 'URL': 'https://www.frontiersin.org/articles/10.3389/fcimb.2023.1192512/full', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 5, 15]], 'date-time': '2023-05-15T13:30:33Z', 'timestamp': 1684157433000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.frontiersin.org/articles/10.3389/fcimb.2023.1192512/full'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 5, 15]]}, 'references-count': 37, 'alternative-id': ['10.3389/fcimb.2023.1192512'], 'URL': 'http://dx.doi.org/10.3389/fcimb.2023.1192512', 'relation': {}, 'ISSN': ['2235-2988'], 'subject': ['Infectious Diseases', 'Microbiology (medical)', 'Immunology', 'Microbiology'], 'container-title-short': 'Front. Cell. Infect. Microbiol.', 'published': {'date-parts': [[2023, 5, 15]]}}