Efficacy and safety of a single dose of casirivimab and imdevimab for the prevention of COVID-19 over an 8-month period: a randomised, double-blind, placebo-controlled trial

Chan, Kuo‐Chen; Subramaniam, Danise; DiCioccio, A. Thomas; Chani, Achint; Adepoju, Adebiyi; Mahmood, Adnan; Mortagy, Aisha; Dupljak, Ajla; Baum, Alina; Brown, Alison; Froment, Amy; Hooper, Andrea T.; Margiotta, Andrea; Bombardier, Andrew; Islam, Anita; Smith, Anne K.; Dhillon, A; McMillian, Audra; Breazna, Aurora; Aslam, Ayesha; Carpentino, Barabara; Kowal, Bari; Siliverstein, Barry; Horel, Benjamin; Zhu, Bin; Musser, Bret J.; Bush, Brian; Head, Brian; Snow, Brian; Zhu, Bryan; Debray, Camille; Phillips, Careta; Simiele, Carmella; Lee, Carol; Nienstedt, Carolyn; Trbovic, Caryn F.; Chan, Casey K.; Elliott, Catherine; Fish, Chad; Ni, Charlie; Polidori, Christa; Enciso, Christine; Caira, Christopher; Powell, Christopher F.; Kyratsous, Christos A.; Baum, Cliff; McDonald, Colin; Leigh, Cynthia; Pan, Cynthia X.; Wolken, Dana; Manganello, Danielle; Liu, David; Stein, David; Weinreich, David M.; Hassan, Dawlat; Gulabani, Daya; Fix, Deborah; Leonard, Deborah A.; Sarda, Deepshree; Bonhomme, Denise; Kennedy, Denise; Darcy, Devin; Barron, Dhanalakshmi; Hughes, Diana; Rofail, Diana; Kaur, Dipinder; Ramesh, Divya; Bianco, Dona; Cohen, Donna; Forleo‐Neto, Eduardo; Jean-Baptiste, Edward; Bukhari, Ehsan; Doyle, Eileen; Bucknam, Elizabeth; Labriola-Tomkins, Emily; Nanna, Emily; O'Keefe, Esther Huffman; Gasparino, Evelyn; Fung, Evonne; Isa, Flonza; To, Fung-Yee; Herman, Gary; Yancopouloš, George D.; Bellingham, Georgia; Sumner, Giane; Moggan, Grainne; Power, Grainne; Zeng, Haixia; Mariveles, Hazel; Gonzalez, Heath; Kang, Helen; Noor, Hibo; Minns, Ian; Heirman, Ingeborg; Peszek, Izabella; Donohue, James F.; Rusconi, Jamie C.; Austin, Janice; Parrino, Janie; Yo, Jeannie; McDonnell, Jenna; Hamilton, Jennifer D.; Boarder, Jessica; Wei, Jianguo; Yu, Jingchun; Malia, Joanne; Tucciarone, Joanne; Tyler-Gale, Jodie; Davis, John D.; Strein, John; Cohen, Jonathan B.; Meyer, Jonathan; Ursino, Jordan; Im, Joseph; Tramaglini, Joseph; Wolken, Joseph; Potter, Kaitlyn; Scacalossi, Kaitlyn; Naidu, Kamala; Browning, Karen S.; Rutkowski, Karen; Yau, Karen; Woloshin, Katherine; Lewis-Amezcua, Kelly; Turner, K. C.; Dornheim, Kimberly; Chiu, Kit; Mohan, Kosalai; McGuire, Kristina; Macci, Kristy; Ringleben, Kurt; Mohammadi, Kusha; Foster, Kyle; Knighton, Latora; Lipsich, Leah; Darling, Lindsay; Boersma, Lisa; Cowen, Lisa; Hersh, Lisa; Jackson, Lisa A.; Purcell, Lisa A.; Sherpinsky, Lisa; Lai, Livia; Faria, Lori; Geissler, Lori; Boppert, Louise; Fiske, Lyra; Dickens, Marc; Mancini, Marco; Leigh, Maria Cynthia; O’Brien, Meagan P.; Batchelder, Michael; Klinger, M.I.; Partridge, M.; Tarabocchia, Michel; Wong, Michelle; Rodriguez, Mivianisse; Albizem, Moetaz; O'Byrne, Muriel; Braunstein, Ned; Sarkar, Neena; Stahl, Neil; Deitz, Nicole; Memblatt, Nicole; Shah, Nirav G.; Kumar, Nitin; Herrera, Olga; Adedoyin, Oluchi; Yellin, Ori; Snodgrass, Pamela; Floody, Patrick; D’Ambrosio, Paul J.; Gao, Paul (Xiaobang); Hou, Peijie; Hearld, Philippa; Li, Qin; Kitchenoff, Rachel; Ali, Rakiyya; Iyer, Ramya; Chava, Ravikanth; Alaj, Rinol; Pedraza, Rita; Hamlin, Robert; Hosain, Romana; Gorawala, Ruchin; White, R.; Yu, Ryan; Fogarty, Rylee; Dass, Sairia; Bollini, Sagarika; Ganguly, Samit; DeCicco, Sandra; Patel, Sanket; Cassimaty, Sarah; Somersan-Karakaya, Selin; McCarthy, Shane; Henkel, Sharon; Ali, Shazia; Shapiro, Shelley Geila; Kim, Somang; Nossoughi, Soraya; Bisulco, Stephanie; Elkin, Steven; Long, Steven; Sivapalasingam, Sumathi; Irvin, Susan C.; Wilt, Susan; Min, Tami; Constant, Tatiana; Devins, Theresa; DiCioccio, Thomas; Norton, Thomas; Bernardo, Travis; Chuang, Tzu-Chien; Wei, Victor K.; Nuce, Vinh; Battini, Vishnu; Caldwell, W.; Gao, Xiaobang; Chen, Xin; Tian, Yanmei; Khan, Yasmin; Zhao, Yuming; Kim, Yun-Ji; Dye, Bonnie J.; Hurt, Christopher B.; Burwen, Dale R.; Barouch, Dan H.; Burns, David; Brown, Elizabeth R.; Bar, Katharine J.; Marovich, Mary; Clement, Meredith E.; Cohen, Myron S.; Sista, Nirupama; Barnabas, Ruanne V.; Zwerski, Sheryl

doi:10.1016/s1473-3099(22)00416-9

Cited by 27 publications

(29 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We note that this relationship is predominately driven by observations of one study, where the longest time course of protection was collected (i.e. the relationship is only significant when the Herman et al 14 data is included, Table S3). Fitting a logistic dose-response relationship to this data, we estimated a peak efficacy of 91% (95% CI: 86 – 99%), and concentration for 50% of efficacy of 939-fold in vitro IC50 (95% CI: 135 – 2073) (Table S4).…”

Section: Resultsmentioning

confidence: 96%

“…Another factor affecting our analysis is the different mode of delivery of the monoclonal antibodies. Casirivimab/imdevimab was administered subcutaneously in the Isa 5 , O’Brien 6 and Herman 14 studies, whereas tixagevimab/cilgavimab was administered intramuscularly in the Levin study 4 . Plasma antibody concentrations had much slower increases following intramuscular administration of tixagevimab/cilgavimab compared with subcutaneous administration of casirivimab/imdevimab, and thus it is possible that there is a delay until protective antibody concentrations are achieved (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

“…These studies were in a mixture of true pre-exposure prophylaxis and peri-exposure prophylaxis settings (Table S1). Two studies, O’Brien et al 6 and Herman et al 14 , reported results from the same clinical trial over different follow-up intervals (4 weeks and 8 months respectively). Thus, to avoid duplication of the same trial results, we integrated the results from these studies.…”

Section: Methodsmentioning

confidence: 99%

“…We included only studies where both protection from symptomatic infection and pharmacokinetic information of the monoclonal antibody were provided within the same study. We identified five eligible studies assessing monoclonal antibodies as pre-exposure and peri-exposure prophylaxis for COVID-19 [4][5][6]14,15 (see Table S1). The antibodies used in these studies were casirivimab/imdevimab (3 studies), bamlanivimab, and tixagevimab/cilgavimab.…”

Section: Aggregating Studies Of Monoclonal Antibodies As Prophylaxismentioning

confidence: 99%

See 3 more Smart Citations

Monoclonal antibody levels and protection from COVID-19

Stadler

Burgess

Schlub

et al. 2022

Preprint

View full text Add to dashboard Cite

Multiple monoclonal antibodies have been shown to be effective for both prophylaxis and therapy for SARS-CoV-2 infection. Here we aggregate data from randomized controlled trials assessing the use of monoclonal antibodies in preventing symptomatic SARS-CoV-2 infection. We use data on changes in the in vivo concentration of monoclonal antibodies, and the associated protection from COVID-19, over time to model the dose-response relationship of monoclonal antibodies for prophylaxis. We estimate that 50% protection from COVID-19 is achieved with a monoclonal antibody concentration of 939-fold of the in vitro IC50 (95% CI: 135 - 2073). This relationship provides a quantitative tool allowing prediction of the prophylactic efficacy and duration of protection for new monoclonal antibodies administered at different doses and against different SARS-CoV-2 variants. Finally, we compare the relationship between neutralization titer and protection from COVID-19 after either monoclonal antibody treatment or vaccination. We find no evidence for a difference between the 50% protective titer for monoclonal antibodies and vaccination, although vaccination is predicted to be capable of achieving a higher maximum level of protection.

show abstract

Section: Resultsmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Aggregating Studies Of Monoclonal Antibodies As Prophylaxismentioning

confidence: 99%

See 2 more Smart Citations

Monoclonal antibody levels and protection from COVID-19

Stadler

Burgess

Schlub

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Moreover, although accurate information regarding the pros and cons of vaccines is not currently available, various COVID-19 vaccines have shown good efficacy in preventing SARS-CoV-2 infection and reducing disease severity and mortality ( 21 – 23 ). The anti-SARS-CoV-2 monoclonal antibodies demonstrated positive effects in pre-exposure prophylaxis against susceptible variants ( 24 ), prevention of progression to severe COVID-19 ( 25 ), and reduction of patient mortality ( 26 ). In addition, because it can recognize the receptor binding domain (RBD) or other SARS-CoV-2 receptors, nanobodies have also been developed to detect the spike proteins of SARS-CoV-2 variants including Omicron ( 27 ), and show the potential of neutralizing SARS-CoV-2 variants ( 28 – 31 ).…”

Section: Introductionmentioning

confidence: 99%

Uncovering the information immunology journals transmitted for COVID-19: A bibliometric and visualization analysis

et al. 2022

View full text Add to dashboard Cite

BackgroundSince the global epidemic of the coronavirus disease 2019 (COVID-19), a large number of immunological studies related to COVID-19 have been published in various immunology journals. However, the results from these studies were discrete, and no study summarized the important immunological information about COVID-19 released by these immunology journals. This study aimed to comprehensively summarize the knowledge structure and research hotspots of COVID-19 published in major immunology journals through bibliometrics.MethodsPublications on COVID-19 in major immunology journals were obtained from the Web of Science Core Collection. CiteSpace, VOSviewer, and R-bibliometrix were comprehensively used for bibliometric and visual analysis.Results1,331 and 5,000 publications of 10 journals with high impact factors and 10 journals with the most papers were included, respectively. The USA, China, England, and Italy made the most significant contributions to these papers. University College London, National Institute of Allergy and Infectious Diseases, Harvard Medical School, University California San Diego, and University of Pennsylvania played a central role in international cooperation in the immunology research field of COVID-19. Yuen Kwok Yung was the most important author in terms of the number of publications and citations, and the H-index. CLINICAL INFECTIOUS DISEASES and FRONTIERS IN IMMUNOLOGY were the most essential immunology journals. These immunology journals mostly focused on the following topics: “Delta/Omicron variants”, “cytokine storm”, “neutralization/neutralizing antibody”, “T cell”, “BNT162b2”, “mRNA vaccine”, “vaccine effectiveness/safety”, and “long COVID”.ConclusionThis study systematically uncovered a holistic picture of the current research on COVID-19 published in major immunology journals from the perspective of bibliometrics, which will provide a reference for future research in this field.

show abstract

Mycophenolic Acid Exposure Determines Antibody Formation Following SARS‐CoV‐2 Vaccination in Kidney Transplant Recipients: A Nested Cohort Study

Meziyerh

Bouwmans

Gelder

et al. 2023

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

Despite (repeated) boosting, kidney transplant recipients (KTRs) may remain at increased risk of severe COVID-19 since a substantial number of individuals remain seronegative or with low antibody titers. In particular, mycophenolic acid use has been shown to affect antibody formation negatively and may be an important modifiable risk factor. We investigated the exposure-response relationship between mycophenolic acid 12-hour area under the curve (AUC 0-12h ) exposure and seroconversion including antibody titers after vaccination using mRNA-1273 SARS-CoV-2 vaccine (Moderna) in 316 KTRs from our center that participated in the national Dutch renal patients COVID-19 vaccination -long term efficacy and safety of SARS-CoV-2 vaccination in kidney disease patients vaccination study. After two vaccination doses, 162 (51%) KTRs seroconverted. KTRs treated with mycophenolic acid showed less seroconversion and lower antibody titers compared with KTRs without mycophenolic acid (44% vs. 77%, and 36 binding antibody units (BAU)/mL vs. 340 BAU/mL; P < 0.001). The mean mycophenolic acid AUC 0-12h exposure was significantly lower in KTRs who seroconverted compared with KTRs who did not (39 vs. 29 mg⋅h/L; P < 0.001). High mycophenolic acid exposure (±90 mg⋅h/L) and no exposure to mycophenolic acid resulted in a seroconversion rate ranging from 10% to 80%. Every 10 mg⋅h/L increase in mycophenolic acid AUC 0-12h gave an adjusted odds ratio for seroconversion of 0.87 (95% confidence interval (CI), 0.79-0.97; P = 0.010) and 0.89 (95% CI, 0.85-0.93; P < 0.001) for KTRs on dual and triple maintenance immunosuppressive therapy, respectively. Higher mycophenolic acid AUC 0-12h correlated with lower antibody titers (R = 0.44, P < 0.001). This study demonstrates the exposure-response relationship between gold standard mycophenolic acid exposure and antibody formation to support interventional studies investigating mycophenolic acid adjustment to improve antibody formation after further boosting.

show abstract

Efficacy and safety of a single dose of casirivimab and imdevimab for the prevention of COVID-19 over an 8-month period: a randomised, double-blind, placebo-controlled trial

Cited by 27 publications

References 14 publications

Monoclonal antibody levels and protection from COVID-19

Monoclonal antibody levels and protection from COVID-19

Uncovering the information immunology journals transmitted for COVID-19: A bibliometric and visualization analysis

Mycophenolic Acid Exposure Determines Antibody Formation Following SARS‐CoV‐2 Vaccination in Kidney Transplant Recipients: A Nested Cohort Study

Contact Info

Product

Resources

About