Real-world Effectiveness and Tolerability of Monoclonal Antibody Therapy for Ambulatory Patients With Early COVID-19
MD Brandon J Webb, Whitney Buckel, Todd Vento, Allison M Butler, Nancy Grisel, Samuel M Brown, Ithan D Peltan, Emily S Spivak, Mark Shah, Theadora Sakata, Anthony Wallin, Eddie Stenehjem, Greg Poulsen, Joseph Bledsoe
Open Forum Infectious Diseases, doi:10.1093/ofid/ofab331
Background. Neutralizing monoclonal antibodies (MAbs) are a promising therapy for early coronavirus disease 2019 , but their effectiveness has not been confirmed in a real-world setting. Methods. In this quasi-experimental pre-/postimplementation study, we estimated the effectiveness of MAb treatment within 7 days of symptom onset in high-risk ambulatory adults with COVID-19. The primary outcome was a composite of emergency department visits or hospitalizations within 14 days of positive test. Secondary outcomes included adverse events and 14-day mortality. The average treatment effect in the treated for MAb therapy was estimated using inverse probability of treatment weighting and the impact of MAb implementation using propensity-weighted interrupted time series analysis. Results. Pre-implementation (July-November 2020), 7404 qualifying patients were identified. Postimplementation (December 2020-January 2021), 594 patients received MAb treatment and 5536 did not. The primary outcome occurred in 75 (12.6%) MAb recipients, 1018 (18.4%) contemporaneous controls, and 1525 (20.6%) historical controls. MAb treatment was associated with decreased likelihood of emergency care or hospitalization (odds ratio, 0.69; 95% CI, 0.60-0.79). After implementation, the weighted probability that a given patient would require an emergency department visit or hospitalization decreased significantly (0.7% per day; 95% CI, 0.03%-0.10%). Mortality was 0.2% (n = 1) in the MAb group compared with 1.0% (n = 71) and 1.0% (n = 57) in pre-and postimplementation controls, respectively. Adverse events occurred in 7 (1.2%); 2 (0.3%) were considered serious. Conclusions. MAb treatment of high-risk ambulatory patients with early COVID-19 was well tolerated and likely effective at preventing the need for subsequent emergency department or hospital care.
Supplementary Data Supplementary materials are available at Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.
References
Austin, Stuart, Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies, Stat Med
Cevik, Tate, Lloyd, SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis, Lancet Microbe
Charlson, Pompei, Ales, Mackenzie, A new method of classifying prognostic comorbidity in longitudinal studies: development and validation, J Chronic Dis
Chatellier, Zapletal, Lemaitre, The number needed to treat: a clinically useful nomogram in its proper context, BMJ
Chen, Nirula, Heller, BLAZE-1 Investigators. SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with Covid-19, N Engl J Med
Elixhauser, Steiner, Harris, Coffey, Comorbidity measures for use with administrative data, Med Care
Gottlieb, Nirula, Chen, 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, JAMA
Libster, Marc, Wappner, Fundación INFANT-COVID-19 Group. Early high-titer plasma therapy to prevent severe Covid-19 in older adults, N Engl J Med
Rubin, Estimating causal effects from large data sets using propensity scores, Ann Intern Med
Wagner, Soumerai, Zhang, Ross-Degnan, Segmented regression analysis of interrupted time series studies in medication use research, J Clin Pharm Ther
Webb, Levin, Grisel, Simple scoring tool to estimate risk of hospitalization and mortality in ambulatory and emergency department patients with COVID-19, MedRxiv,
doi:10.1101/2021.02.22.21252171Weinreich, Sivapalasingam, Norton, Trial Investigators. REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19, N Engl J Med
{ 'indexed': {'date-parts': [[2024, 3, 11]], 'date-time': '2024-03-11T21:07:10Z', 'timestamp': 1710191230929},
'reference-count': 15,
'publisher': 'Oxford University Press (OUP)',
'issue': '7',
'license': [ { 'start': { 'date-parts': [[2021, 6, 23]],
'date-time': '2021-06-23T00:00:00Z',
'timestamp': 1624406400000},
'content-version': 'vor',
'delay-in-days': 0,
'URL': 'http://creativecommons.org/licenses/by-nc-nd/4.0/'}],
'content-domain': {'domain': [], 'crossmark-restriction': False},
'published-print': {'date-parts': [[2021, 7, 1]]},
'abstract': '<jats:title>Abstract</jats:title>\n'
' <jats:sec>\n'
' <jats:title>Background</jats:title>\n'
' <jats:p>Neutralizing monoclonal antibodies (MAbs) are a promising therapy '
'for early coronavirus disease 2019 (COVID-19), but their effectiveness has not been confirmed '
'in a real-world setting.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Methods</jats:title>\n'
' <jats:p>In this quasi-experimental pre-/postimplementation study, we '
'estimated the effectiveness of MAb treatment within 7 days of symptom onset in high-risk '
'ambulatory adults with COVID-19. The primary outcome was a composite of emergency department '
'visits or hospitalizations within 14 days of positive test. Secondary outcomes included '
'adverse events and 14-day mortality. The average treatment effect in the treated for MAb '
'therapy was estimated using inverse probability of treatment weighting and the impact of MAb '
'implementation using propensity-weighted interrupted time series analysis.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Results</jats:title>\n'
' <jats:p>Pre-implementation (July–November 2020), 7404 qualifying patients '
'were identified. Postimplementation (December 2020–January 2021), 594 patients received MAb '
'treatment and 5536 did not. The primary outcome occurred in 75 (12.6%) MAb recipients, 1018 '
'(18.4%) contemporaneous controls, and 1525 (20.6%) historical controls. MAb treatment was '
'associated with decreased likelihood of emergency care or hospitalization (odds ratio, 0.69; '
'95% CI, 0.60–0.79). After implementation, the weighted probability that a given patient would '
'require an emergency department visit or hospitalization decreased significantly (0.7% per '
'day; 95% CI, 0.03%–0.10%). Mortality was 0.2% (n\u2005=\u20051) in the MAb group compared '
'with 1.0% (n\u2005=\u200571) and 1.0% (n\u2005=\u200557) in pre- and postimplementation '
'controls, respectively. Adverse events occurred in 7 (1.2%); 2 (0.3%) were considered '
'serious.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Conclusions</jats:title>\n'
' <jats:p>MAb treatment of high-risk ambulatory patients with early COVID-19 '
'was well tolerated and likely effective at preventing the need for subsequent emergency '
'department or hospital care.</jats:p>\n'
' </jats:sec>',
'DOI': '10.1093/ofid/ofab331',
'type': 'journal-article',
'created': {'date-parts': [[2021, 6, 23]], 'date-time': '2021-06-23T01:00:39Z', 'timestamp': 1624410039000},
'source': 'Crossref',
'is-referenced-by-count': 42,
'title': 'Real-world Effectiveness and Tolerability of Monoclonal Antibody Therapy for Ambulatory Patients '
'With Early COVID-19',
'prefix': '10.1093',
'volume': '8',
'author': [ { 'ORCID': 'http://orcid.org/0000-0002-1799-3315',
'authenticated-orcid': False,
'given': 'Brandon J',
'family': 'Webb',
'sequence': 'first',
'affiliation': [ { 'name': 'Division of Infectious Diseases and Clinical Epidemiology, '
'Intermountain Healthcare, Salt Lake City, Utah, USA'},
{ 'name': 'Division of Infectious Diseases and Geographic Medicine, '
'Stanford Medicine, Palo Alto, California, USA'}]},
{ 'given': 'Whitney',
'family': 'Buckel',
'sequence': 'additional',
'affiliation': [ { 'name': 'Pharmacy Services, Intermountain Healthcare, Salt Lake City, '
'Utah, USA'}]},
{ 'given': 'Todd',
'family': 'Vento',
'sequence': 'additional',
'affiliation': [ { 'name': 'Division of Infectious Diseases and Clinical Epidemiology, '
'Intermountain Healthcare, Salt Lake City, Utah, USA'}]},
{ 'given': 'Allison M',
'family': 'Butler',
'sequence': 'additional',
'affiliation': [ { 'name': 'Enterprise Analytics, Intermountain Healthcare, Salt Lake City, '
'Utah, USA'}]},
{ 'given': 'Nancy',
'family': 'Grisel',
'sequence': 'additional',
'affiliation': [ { 'name': 'Enterprise Analytics, Intermountain Healthcare, Salt Lake City, '
'Utah, USA'}]},
{ 'given': 'Samuel M',
'family': 'Brown',
'sequence': 'additional',
'affiliation': [ { 'name': 'Division of Pulmonary and Critical Care Medicine, Intermountain '
'Medical Center and University of Utah, Salt Lake City, Utah, '
'USA'}]},
{ 'given': 'Ithan D',
'family': 'Peltan',
'sequence': 'additional',
'affiliation': [ { 'name': 'Division of Pulmonary and Critical Care Medicine, Intermountain '
'Medical Center and University of Utah, Salt Lake City, Utah, '
'USA'}]},
{ 'given': 'Emily S',
'family': 'Spivak',
'sequence': 'additional',
'affiliation': [ { 'name': 'Division of Infectious Diseases, University of Utah School of '
'Medicine, Salt Lake City, Utah, USA'}]},
{ 'given': 'Mark',
'family': 'Shah',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Emergency Medicine, Intermountain Healthcare, Salt '
'Lake City, Utah, USA'}]},
{ 'given': 'Theadora',
'family': 'Sakata',
'sequence': 'additional',
'affiliation': [ { 'name': 'Urgent Care Service Line, Intermountain Healthcare, Salt Lake '
'City, Utah, USA'}]},
{ 'given': 'Anthony',
'family': 'Wallin',
'sequence': 'additional',
'affiliation': [ { 'name': 'Urgent Care Service Line, Intermountain Healthcare, Salt Lake '
'City, Utah, USA'}]},
{ 'given': 'Eddie',
'family': 'Stenehjem',
'sequence': 'additional',
'affiliation': [ { 'name': 'Division of Infectious Diseases and Clinical Epidemiology, '
'Intermountain Healthcare, Salt Lake City, Utah, USA'},
{ 'name': 'Division of Infectious Diseases and Geographic Medicine, '
'Stanford Medicine, Palo Alto, California, USA'},
{ 'name': 'Office of Patient Experience, Intermountain Healthcare, Salt '
'Lake City, Utah, USA'}]},
{ 'given': 'Greg',
'family': 'Poulsen',
'sequence': 'additional',
'affiliation': [ { 'name': 'Executive Leadership Team, Intermountain Healthcare, Salt Lake '
'City, Utah, USA'}]},
{ 'given': 'Joseph',
'family': 'Bledsoe',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Emergency Medicine, Intermountain Healthcare, Salt '
'Lake City, Utah, USA'},
{ 'name': 'Department of Emergency Medicine, Stanford Medicine, Palo Alto, '
'California, USA'}]}],
'member': '286',
'published-online': {'date-parts': [[2021, 6, 23]]},
'reference': [ { 'key': '2021072712513475600_CIT0001',
'doi-asserted-by': 'crossref',
'first-page': '880',
'DOI': '10.1001/jama.2020.24415',
'article-title': 'An EUA for bamlanivimab—a monoclonal',
'volume': '325',
'year': '2021',
'journal-title': 'JAMA'},
{ 'key': '2021072712513475600_CIT0002',
'first-page': '201',
'article-title': 'An EUA for casirivimab and imdevimab for COVID-19',
'volume': '62',
'year': '2020',
'journal-title': 'Med Lett Drugs Ther'},
{ 'key': '2021072712513475600_CIT0003',
'doi-asserted-by': 'crossref',
'first-page': '229',
'DOI': '10.1056/NEJMoa2029849',
'article-title': 'SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with Covid-19',
'volume': '384',
'author': 'Chen',
'year': '2021',
'journal-title': 'N Engl J Med'},
{ 'key': '2021072712513475600_CIT0004',
'doi-asserted-by': 'crossref',
'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': '2021072712513475600_CIT0005',
'doi-asserted-by': 'crossref',
'first-page': '238',
'DOI': '10.1056/NEJMoa2035002',
'article-title': 'REGN-COV2, a neutralizing antibody cocktail, in outpatients with '
'Covid-19',
'volume': '384',
'author': 'Weinreich',
'year': '2021',
'journal-title': 'N Engl J Med'},
{ 'key': '2021072712513475600_CIT0006',
'doi-asserted-by': 'crossref',
'first-page': '373',
'DOI': '10.1016/0021-9681(87)90171-8',
'article-title': 'A new method of classifying prognostic comorbidity in longitudinal '
'studies: development and validation',
'volume': '40',
'author': 'Charlson',
'year': '1987',
'journal-title': 'J Chronic Dis'},
{ 'key': '2021072712513475600_CIT0007',
'doi-asserted-by': 'crossref',
'first-page': '8',
'DOI': '10.1097/00005650-199801000-00004',
'article-title': 'Comorbidity measures for use with administrative data',
'volume': '36',
'author': 'Elixhauser',
'year': '1998',
'journal-title': 'Med Care'},
{ 'key': '2021072712513475600_CIT0008',
'volume-title': 'Utah Department of Health and Utah Hospital Association'},
{ 'key': '2021072712513475600_CIT0009',
'article-title': 'Simple scoring tool to estimate risk of hospitalization and mortality '
'in ambulatory and emergency department patients with COVID-19',
'author': 'Webb',
'year': '2021',
'journal-title': 'MedRxiv'},
{ 'key': '2021072712513475600_CIT0010',
'doi-asserted-by': 'crossref',
'first-page': '757',
'DOI': '10.7326/0003-4819-127-8_Part_2-199710151-00064',
'article-title': 'Estimating causal effects from large data sets using propensity scores',
'volume': '127',
'author': 'Rubin',
'year': '1997',
'journal-title': 'Ann Intern Med'},
{ 'key': '2021072712513475600_CIT0011',
'doi-asserted-by': 'crossref',
'first-page': '3661',
'DOI': '10.1002/sim.6607',
'article-title': 'Moving towards best practice when using inverse probability of '
'treatment weighting (IPTW) using the propensity score to estimate '
'causal treatment effects in observational studies',
'volume': '34',
'author': 'Austin',
'year': '2015',
'journal-title': 'Stat Med'},
{ 'key': '2021072712513475600_CIT0012',
'doi-asserted-by': 'crossref',
'first-page': '426',
'DOI': '10.1136/bmj.312.7028.426',
'article-title': 'The number needed to treat: a clinically useful nomogram in its proper '
'context',
'volume': '312',
'author': 'Chatellier',
'year': '1996',
'journal-title': 'BMJ'},
{ 'key': '2021072712513475600_CIT0013',
'doi-asserted-by': 'crossref',
'first-page': '299',
'DOI': '10.1046/j.1365-2710.2002.00430.x',
'article-title': 'Segmented regression analysis of interrupted time series studies in '
'medication use research',
'volume': '27',
'author': 'Wagner',
'year': '2002',
'journal-title': 'J Clin Pharm Ther'},
{ 'key': '2021072712513475600_CIT0014',
'doi-asserted-by': 'crossref',
'first-page': '610',
'DOI': '10.1056/NEJMoa2033700',
'article-title': 'Early high-titer plasma therapy to prevent severe Covid-19 in older '
'adults',
'volume': '384',
'author': 'Libster',
'year': '2021',
'journal-title': 'N Engl J Med'},
{ 'key': '2021072712513475600_CIT0015',
'doi-asserted-by': 'crossref',
'first-page': 'e13',
'DOI': '10.1016/S2666-5247(20)30172-5',
'article-title': 'SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of '
'viral shedding, and infectiousness: a systematic review and '
'meta-analysis',
'volume': '2',
'author': 'Cevik',
'year': '2021',
'journal-title': 'Lancet Microbe'}],
'container-title': 'Open Forum Infectious Diseases',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'http://academic.oup.com/ofid/advance-article-pdf/doi/10.1093/ofid/ofab331/38814041/ofab331.pdf',
'content-type': 'application/pdf',
'content-version': 'am',
'intended-application': 'syndication'},
{ 'URL': 'http://academic.oup.com/ofid/article-pdf/8/7/ofab331/39337375/ofab331.pdf',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'syndication'},
{ 'URL': 'http://academic.oup.com/ofid/article-pdf/8/7/ofab331/39337375/ofab331.pdf',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2021, 7, 27]],
'date-time': '2021-07-27T12:52:09Z',
'timestamp': 1627390329000},
'score': 1,
'resource': {'primary': {'URL': 'https://academic.oup.com/ofid/article/doi/10.1093/ofid/ofab331/6308074'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2021, 6, 23]]},
'references-count': 15,
'journal-issue': {'issue': '7', 'published-print': {'date-parts': [[2021, 7, 1]]}},
'URL': 'http://dx.doi.org/10.1093/ofid/ofab331',
'relation': { 'has-preprint': [ { 'id-type': 'doi',
'id': '10.1101/2021.03.15.21253646',
'asserted-by': 'object'}]},
'ISSN': ['2328-8957'],
'subject': ['Infectious Diseases', 'Oncology'],
'published-other': {'date-parts': [[2021, 7, 1]]},
'published': {'date-parts': [[2021, 6, 23]]}}
