The impact of COVID-19 monoclonal antibodies on clinical outcomes: A retrospective cohort study
Nagler, Arielle R; Horwitz, Leora I; Jones, Simon; Petrilli, Christopher M; Iturrate, Eduardo; Lighter, Jennifer L; Phillips, Michael; Bosworth, Brian P; Polsky, Bruce; Volpicelli, Frank M; Dapkins, Isaac; Viswanathan, Anand; François, Fritz; Kalkut, Gary
DISCLAIMER/CONCLUSIONS:In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE/OBJECTIVE:Despite progress in the treatment of coronavirus disease 2019 (COVID-19), including the development of monoclonal antibodies (mAbs), more clinical data to support the use of mAbs in outpatients with COVID-19 is needed. This study is designed to determine the impact of bamlanivimab, bamlanivimab/etesevimab, or casirivimab/imdevimab on clinical outcomes within 30 days of COVID-19 diagnosis. METHODS:A retrospective cohort study was conducted at a single academic medical center with 3 campuses in Manhattan, Brooklyn, and Long Island, NY. Patients 12 years of age or older who tested positive for COVID-19 or were treated with a COVID-19-specific therapy, including COVID-19 mAb therapies, at the study site between November 24, 2020, and May 15, 2021, were included. The primary outcomes included rates of emergency department (ED) visit, inpatient admission, intensive care unit (ICU) admission, or death within 30 days from the date of COVID-19 diagnosis. RESULTS:A total of 1,344 mAb-treated patients were propensity matched to 1,344 patients with COVID-19 patients who were not treated with mAb therapy. Within 30 days of diagnosis, among the patients who received mAb therapy, 101 (7.5%) presented to the ED and 79 (5.9%) were admitted. Among the patients who did not receive mAb therapy, 165 (12.3%) presented to the ED and 156 (11.6%) were admitted (relative risk [RR], 0.61 [95% CI, 0.50-0.75] and 0.51 [95% CI, 0.40-0.64], respectively). Four mAb patients (0.3%) and 2.64 control patients (0.2%) were admitted to the ICU (RR, 01.51; 95% CI, 0.45-5.09). Six mAb-treated patients (0.4%) and 3.37 controls (0.3%) died and/or were admitted to hospice (RR, 1.61; 95% CI, 0.54-4.83). mAb therapy in ambulatory patients with COVID-19 decreases the risk of ED presentation and hospital admission within 30 days of diagnosis.
PMCID:9619808
PMID: 36242772
ISSN: 1535-2900
CID: 5361302
Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial
Wolfe, Cameron R; Tomashek, Kay M; Patterson, Thomas F; Gomez, Carlos A; Marconi, Vincent C; Jain, Mamta K; Yang, Otto O; Paules, Catharine I; Palacios, Guillermo M Ruiz; Grossberg, Robert; Harkins, Michelle S; Mularski, Richard A; Erdmann, Nathaniel; Sandkovsky, Uriel; Almasri, Eyad; Pineda, Justino Regalado; Dretler, Alexandra W; de Castilla, Diego Lopez; Branche, Angela R; Park, Pauline K; Mehta, Aneesh K; Short, William R; McLellan, Susan L F; Kline, Susan; Iovine, Nicole M; El Sahly, Hana M; Doernberg, Sarah B; Oh, Myoung-Don; Huprikar, Nikhil; Hohmann, Elizabeth; Kelley, Colleen F; Holodniy, Mark; Kim, Eu Suk; Sweeney, Daniel A; Finberg, Robert W; Grimes, Kevin A; Maves, Ryan C; Ko, Emily R; Engemann, John J; Taylor, Barbara S; Ponce, Philip O; Larson, LuAnn; Melendez, Dante Paolo; Seibert, Allan M; Rouphael, Nadine G; Strebe, Joslyn; Clark, Jesse L; Julian, Kathleen G; de Leon, Alfredo Ponce; Cardoso, Anabela; de Bono, Stephanie; Atmar, Robert L; Ganesan, Anuradha; Ferreira, Jennifer L; Green, Michelle; Makowski, Mat; Bonnett, Tyler; Beresnev, Tatiana; Ghazaryan, Varduhi; Dempsey, Walla; Nayak, Seema U; Dodd, Lori E; Beigel, John H; Kalil, Andre C; Wahid, Lana; Walter, Emmanuel B; Belur, Akhila G; Dreyer, Grace; Patterson, Jan E; Bowling, Jason E; Dixon, Danielle O; Hewlett, Angela; Odrobina, Robert; Pupaibool, Jakrapun; Mocherla, Satish; Lazarte, Suzana; Cayabyab, Meilani; Hussein, Rezhan H; Golamari, Reshma R; Krill, Kaleigh L; Rajme, Sandra; Riska, Paul F; Zingman, Barry S; Mertz, Gregory; Sosa, Nestor; Goepfert, Paul A; Berhe, Mezgebe; Dishner, Emma; Fayed, Mohamed; Hubel, Kinsley; Martinez-Orozco, José Arturo; Bautista Felix, Nora; Elmor, Sammy T; Bechnak, Amer Ryan; Saklawi, Youssef; Van Winkle, Jason W; Zea, Diego F; Laguio-Vila, Maryrose; Walsh, Edward E; Falsey, Ann R; Carvajal, Karen; Hyzy, Robert C; Hanna, Sinan; Olbrich, Norman; Traenkner, Jessica J; Kraft, Colleen S; Tebas, Pablo; Baron, Jillian T; Levine, Corri; Nock, Joy; Billings, Joanne; Kim, Hyun; Elie-Turenne, Marie-Carmelle; Whitaker, Jennifer A; Luetkemeyer, Anne F; Dwyer, Jay; Bainbridge, Emma; Gyun Choe, Pyoeng; Kyung Kang, Chang; Jilg, Nikolaus; Cantos, Valeria D; Bhamidipati, Divya R; Nithin Gopalsamy, Srinivasa; Chary, Aarthi; Jung, Jongtak; Song, Kyoung-Ho; Kim, Hong Bin; Benson, Constance A; McConnell, Kimberly; Wang, Jennifer P; Wessolossky, Mireya; Perez, Katherine; Eubank, Taryn A; Berjohn, Catherine; Utz, Gregory C; Jackson, Patrick E H; Bell, Taison D; Haughey, Heather M; Moanna, Abeer; Cribbs, Sushma; Harrison, Telisha; Colombo, Christopher J; Schofield, Christina; Colombo, Rhonda E; Tapson, Victor F; Grein, Jonathan; Sutterwala, Fayyaz; Ince, Dilek; Winokur, Patricia L; Fung, Monica; Jang, Hannah; Wyles, David; Frank, Maria G; Sarcone, Ellen; Neumann, Henry; Viswanathan, Anand; Hochman, Sarah; Mulligan, Mark; Eckhardt, Benjamin; Carmody, Ellie; Ahuja, Neera; Nadeau, Kari; Svec, David; Macaraeg, Jeffrey C; Morrow, Lee; Quimby, Dave; Bessesen, Mary; Nicholson, Lindsay; Adams, Jill; Kumar, Princy; Lambert, Allison A; Arguinchona, Henry; Alicic, Radica Z; Saito, Sho; Ohmagari, Norio; Mikami, Ayako; Chien Lye, David; Hong Lee, Tau; Ying Chia, Po; Hsieh, Lanny; Amin, Alpesh N; Watanabe, Miki; Candiotti, Keith A; Castro, Jose G; Antor, Maria A; Lee, Tida; Lalani, Tahaniyat; Novak, Richard M; Wendrow, Andrea; Borgetti, Scott A; George, Sarah L; Hoft, Daniel F; Brien, James D; Cohen, Stuart H; Thompson, George R 3rd; Chakrabarty, Melony; Guirgis, Faheem; Davey, Richard T; Voell, Jocelyn; Strich, Jeffrey R; Lindholm, David A; Mende, Katrin; Wellington, Trevor R; Rapaka, Rekha R; Husson, Jennifer S; Levine, Andrea R; Yen Tan, Seow; Shafi, Humaira; Chien, Jaime M F; Hostler, David C; Hostler, Jordanna M; Shahan, Brian T; Adams, David H; Osinusi, Anu; Cao, Huyen; Burgess, Timothy H; Rozman, Julia; Chung, Kevin K; Nieuwoudt, Christina; El-Khorazaty, Jill A; Hill, Heather; Pettibone, Stephanie; Gettinger, Nikki; Engel, Theresa; Lewis, Teri; Wang, Jing; Deye, Gregory A; Nomicos, Effie; Pikaart-Tautges, Rhonda; Elsafy, Mohamed; Jurao, Robert; Koo, Hyung; Proschan, Michael; Yokum, Tammy; Arega, Janice; Florese, Ruth
BACKGROUND:Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19. METHODS:In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168. FINDINGS/RESULTS:Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012). INTERPRETATION/CONCLUSIONS:In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered. FUNDING/BACKGROUND:National Institute of Allergy and Infectious Diseases.
PMID: 35617986
ISSN: 2213-2619
CID: 5249952