Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia
Author:
O’Halloran Jane A.1, Ko Emily R.2, Anstrom Kevin J.3, Kedar Eyal4, McCarthy Matthew W.5, Panettieri Reynold A.6, Maillo Martin7, Nunez Patricia Segura8, Lachiewicz Anne M.3, Gonzalez Cynthia9, Smith P. Brian10, de Tai Sabina Mendivil-Tuchia11, Khan Akram12, Lora Alfredo J. Mena13, Salathe Matthias14, Capo Gerardo15, Gonzalez Daniel Rodríguez16, Patterson Thomas F.17, Palma Christopher18, Ariza Horacio19, Lima Maria Patelli20, Blamoun John21, Nannini Esteban C.22, Sprinz Eduardo23, Mykietiuk Analia24, Alicic Radica25, Rauseo Adriana M.1, Wolfe Cameron R.2, Witting Britta5, Wang Jennifer P.26, Parra-Rodriguez Luis1, Der Tatyana2, Willsey Kate5, Wen Jun10, Silverstein Adam10, O’Brien Sean M.10, Al-Khalidi Hussein R.10, Maldonado Michael A.27, Melsheimer Richard28, Ferguson William G.29, McNulty Steven E.10, Zakroysky Pearl10, Halabi Susan10, Benjamin Daniel K.10, Butler Sandra30, Atkinson Jane C.9, Adam Stacey J.31, Chang Soju9, LaVange Lisa3, Proschan Michael32, Bozzette Samuel A.9, Powderly William G.1, Patel Mahendra33, Sanyal Arun33, Green Jason33, Wu Huimin33, Linas Benjamin33, Grant Philip33, Iyer Vivek33, Yang Otto33, Balani Bindu33, Parnia Sam33, Dare Ryan33, Morse Caryn G.33, Harris Estelle S.33, Wortmann Glenn33, Hill Nicholas33, Patel Shama33, Garcia-Diaz Julia33, Thapamager Suman33, Devine Megan33, Bojanowski Christine M.33, Meisenberg Barry33, Marshall Gailen33, Dandachi Dima33, Sabin Arick33, Breemo Anthony33, Sinha Suman33, Goss Christopher33, Reece Rebecca33, Aouad Arlette33, Glassman Seth33, Morris Peter33, Patel Bela33, Bello Fatimah33, Cardozo Fernandes Juliana33, Carbajal Oscar33, Ravera Lorena33, Castro Mozar33, Villegas-Chiroque Miguel33, Oscar Riera Fernando33, Camacho Adrian33, Stadnik Claudio33, Gave Jorge33, Biondi Rodrigo33, Gamarra Velarde Ronal33, Cerbino Neto Jose33, Ditondo Juan33, Losso Marcelo H.33, Dolz Mariano33, O’Sullivan Alexandra33, Gavin Brian33, Beumont-Mauviel Maria33, Ca Huyen33, Beci Rose33, Molina Daniel33, Rao Sandhya33, Stock Thomas33, Erhardt William33, Read Sarah33, Springer Jessica33, Presti Rachel33, Thompson Ryley33, Gray Kimberly33, Henry Cathy33, Haile Alem33, Klebert Michael33, Kessels Lisa33, Vehe Kathryn33, Bakos Kristopher33, Spitz Teresa33, Hubert Sara33, Alyatim Raghd33, Schneider Brittany33, Ayres Chapelle33, Spec Andrej33, Blair Laura33, Afghanzada Anita33, Schodl Natalie33, Wahid Lana33, Engemann John J.33, Pinero Gloria33, McLendon-Arvik Beth33, Whitt Lynn33, Shroba Jenny33, Salsgiver Elizabeth33, Alleyne Candace33, Gwak Anna33, Pickell Nicholas33, Spagnoletti Jack33, Goh Samson33, Robb Katharine33, Cenname Michael33, Small Catherine33, Plate Markus33, Burgos Rodrigo33, Lindsey Brenna33, Herald Fischer33, Echeverria Stephanie33, Lewis Dorendra33, Patel Mahesh33, Bengtson Charles D.33, Schmid Andreas33, Lovell Kimberly33, Lovelett Carly33, Soule Daniel33, Jaremczuk Daniel33, Flanagan Jennie33, Murray Cameron33, Sands Kylie33, Flint Kyle33, Mohaddes Sara33, Harrington Caryn33, Broughal Kylie33, Sogoian David33, Cox Karen33, Javeri Heta33, Ponce Philip O.33, Dixon Danielle O.33, Bowling Jason E.33, Patterson Jan E.33, Taylor Barbara S.33, Serrano Ruth C.33, Sallee Kaylin33, Tragus Robin33, Catano Gabriel33, Scholler Irma33, Barajas Rose Ann33, Garcia Armando33, Soileau Bridgette33, Heard Patricia33, Camilo Endo Carvajal Manuel33, Ehwarieme Rukevwe33, Chandramohan Divya33, Cabo Alejandro33, Nawwar Abdelhameed33, Quill Caroline M.33, Choudhury Nayeem33, Arrington Ashley33, Holyfield Isaiah33, Smith Abby33, Brown Glenda33, Varner Kyle33, Baxter Joni33, Roundy Tracy33, Co Mary33, Wessolossky Mireya33, Perez-Velazquez Juan33, Holter-Chakrabarty Jennifer33, Karfonta Brittany33, Anjum Juvaria33, Marathe Jai33, Castagne Myriam33, Mompoint Daniel33, Schroeder Ryan33, Rao Mallika33, Nguyen Johnathan33, Plewa Jake33, Donlinger Sue33, Breslin Marylynn33, Dodson Susan33, Jenkins Mitch33, Williamson John33, Middleton Elizabeth A.33, Tavadze Mai33, Sebhatu Romai33, Pierobon Jessica33, Miller Nate33, Lee John33, Doshi Pratik33, Dentino Andrew33, Martin Jessica33, Hinojosa Erik33, Torres Pablo33, Sanchez Ricardo33, Murga Gladys33, de la Gala Silvana33, Chaiña Jhon33, Ramos Jorge33, Malca Jenny33, Castillo Kathia33, Calderon Galvez Johana33, Icochea Perez Maria Lyda33, Becerra Nunez Claudia Carolina33, Betteta Riondato Sandra33, Delgado Málaga Sandra33, Barreda Sánchez Cecilia33, Sánchez Morales Sylvia33, Yaringano Palacios Myriam33, Galarza Cuba Dora33, Hermenegildo Ivan33, Falla Benites Mayra33, Neyra Stefania33, Hernández Josefina33, García Victoria33, Palacios Katherine33, Matos Miluska33, Zuloeta Fiorella33, del Carpio Fiorella33, Chacaltana Gloria33, de la Cruz Carmen33, Ceriolli Breda Felipe33, Mello Roux Leite Mauricio33, Milbradt Tobias33, Rodeles Luz33, Benzaquen Nadia33, Pezzini Sebastian33, Alberdi Lucila33, Serravalle Priscila33, Russo Giulia33, Ferini Franco33, Guala Maria Eugenia33, Crespo Alejandro33, Benitez Agostina33, Cristaldi Maria Elena33, Di Renzo Paula33, Gramagalia Corina33, Tessini Antonela33, Alonso Joana Evelin33, Pic Carmen33, Ceraldi Georgina33, Mondino Azucena33, Higareda Almaraz Iliana33, Madrigal Robles Víctor Hugo33, Rosas Ismerio María Fernanda33, Rodarte Rodriguez Maria Fernanda33, Olmos Meza Norma Esther33, de la Cruz Barba Norma Esther33, Alba Ponce Ana Maria33, Calderon Juan Manuel33, Borsetta Eduardo33, Sandoval Noemí33, Vazquez Daniela33, Mansilla Malena33, Molina Marta33, Jara Yamila33, De Bona Laura33, Eduarda Claus Maria33, Pille Arthur33, Lahitte Matías33, Fenés Mariángeles33, Bianchi Cecilia33, Miserere María Emilia33, Alzogaray Maria Fernanda33, Christian Sanchez Carrillo Halbert33, Mano Aldana33, Zuain Myrna33, Toibaro Javier J.33, Pachioli Valeria33, Chaio Sebastián33, Malamud Natalia33, Bharucha David B.33, Dorr Patrick33, Sadeh Jonathan33, Kelly Sheila33, Stevens Marita33, Cao Huyen33, DeZure Adam33, Juneja Kavita33, Abdelghany Mazin33, Jasion Theresa33, Olson Rachel33, Roebuck Megan33, Huvane Jacqueline33, Lindsell Christopher J.33, Leimberger Jeff33, Yow Eric33, Huang Zhen33, Kim Hwasoon33, Anderson Carla33, Elliott Carrie33, Swartz Merri33, Garg Jyotsna33, Nelson Neta33, Kalaria Divya33, Philogene Ketty33, Schulz Tim33, Kuek Averie33, Bah Fatou33, Mitchell Jarrard33, Polo Elizabeth33, Wong Michelle33, Baldan Sharon33, Mendez Sandra33, Stevens Bradford33, Toledo Marcela33, Abba Talita33, Herrejon Emma33, Gomez Cristina33, Mardari Georgeta33, Putta Neeraja33, Mason Robin33, Hamilton Holli33, Eisnor Derek33, O’Rourke Anna33, Patel Aditi33, Brody Betty33, Chiang Anna33, Lind Brian33, Portilla Lilli M.33, Gadhia Ami D.33, Vepa Sury33, Carlson Marti Emily33, Gardner Bobbi33, Rutter Joni33, Schmitt Clare33, Kurilla Michael33,
Affiliation:
1. Washington University St Louis, St Louis, Missouri 2. Duke University Health System, Durham, North Carolina 3. University of North Carolina, Chapel Hill 4. St Lawrence Health, Potsdam, New York 5. Weill Cornell Medicine, New York, New York 6. Robert Wood Johnson Medical School, New Brunswick, New Jersey 7. Sanatorio Diagnostico, Santa Fe, Argentina 8. Hospital Nacional Hipolito Unanue, Lima, Peru 9. National Center for Advancing Translational Sciences, Bethesda, Maryland 10. Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina 11. Hospital Central de la Fuerza Aerea del Peru, Lima, Peru 12. Oregon Health and Science University, Portland 13. University of Illinois at Chicago 14. University of Kansas Medical Center, Kansas City 15. Trinitas Hospital, Elizabeth, New Jersey 16. Nuevo Hospital Civil de Guadalajara Juan I. Menchaca, Guadalajara, Mexico 17. University of Texas Health Science Center at San Antonio 18. University of Rochester School of Medicine and Dentistry, Rochester, New York 19. Clinica Central SA, Villa Regina, Argentina 20. Hospital e Maternidade Celso Pierro—PUC Campinas, Campinas, Brazil 21. MidMichigan Medical Center, Midland 22. Sanatorio Britanico, Santa Fe, Argentina 23. Hospital de Clinicas de Porto Alegre HCPA, Porto Alegre, Brazil 24. Instituto Medico Platense, La Plata, Argentina 25. Providence Medical Research Center, Spokane, Washington 26. University of Massachusetts Medical Center, Worcester 27. Bristol Myers Squibb, Philadelphia, Pennsylvania 28. Janssen Pharmaceuticals, Leiden, the Netherlands 29. AbbVie, Inc, North Chicago, Illinois 30. Technical Resources International (TRI), Bethesda, Maryland 31. Foundation for the National Institutes of Health, Bethesda, Maryland 32. National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 33. for the ACTIV-1 IM Study Group Members
Abstract
ImportanceImmune dysregulation contributes to poorer outcomes in COVID-19.ObjectiveTo investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.Design, Setting, and ParticipantsRandomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021.InterventionsSingle infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day).Main Outcomes and MeasuresThe primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale.ResultsOf the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies.Conclusions and RelevanceTime to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo.Trial RegistrationClinicalTrials.gov Identifier: NCT04593940
Publisher
American Medical Association (AMA)
Cited by
12 articles.
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