Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia
Authors: O’Halloran Jane A. , Ko Emily R. , Anstrom Kevin J. , Kedar Eyal , McCarthy Matthew W. , Panettieri Reynold A. , Maillo Martin , Nunez Patricia Segura , Lachiewicz Anne M. , Gonzalez Cynthia , Smith P. Brian , de Tai Sabina Mendivil-Tuchia , Khan Akram , Lora Alfredo J. Mena , Salathe Matthias , Capo Gerardo , Gonzalez Daniel Rodríguez , Patterson Thomas F. , Palma Christopher , Ariza Horacio , Lima Maria Patelli , Blamoun John , Nannini Esteban C. , Sprinz Eduardo , Mykietiuk Analia , Alicic Radica , Rauseo Adriana M. , Wolfe Cameron R. , Witting Britta , Wang Jennifer P. , Parra-Rodriguez Luis , Der Tatyana , Willsey Kate , Wen Jun , Silverstein Adam , O’Brien Sean M. , Al-Khalidi Hussein R. , Maldonado Michael A. , Melsheimer Richard , Ferguson William G. , McNulty Steven E. , Zakroysky Pearl , Halabi Susan , Benjamin Daniel K. , Butler Sandra , Atkinson Jane C. , Adam Stacey J. , Chang Soju , LaVange Lisa , Proschan Michael , Bozzette Samuel A. , Powderly William G. ,   ACTIV-1 IM Study Group Members, Patel Mahendra , Sanyal Arun , Green Jason , Wu Huimin , Linas Benjamin , Grant Philip , Iyer Vivek , Yang Otto , Balani Bindu , Parnia Sam , Dare Ryan , Morse Caryn G. , Harris Estelle S. , Wortmann Glenn , Hill Nicholas , Patel Shama , Garcia-Diaz Julia , Thapamager Suman , Devine Megan , Bojanowski Christine M. , Meisenberg Barry , Marshall Gailen , Dandachi Dima , Sabin Arick , Breemo Anthony , Sinha Suman , Goss Christopher , Reece Rebecca , Aouad Arlette , Glassman Seth , Morris Peter , Patel Bela , Bello Fatimah , Cardozo Fernandes Juliana , Carbajal Oscar , Ravera Lorena , Castro Mozar , Villegas-Chiroque Miguel , Oscar Riera Fernando , Camacho Adrian , Stadnik Claudio , Gave Jorge , Biondi Rodrigo , Gamarra Velarde Ronal , Cerbino Neto Jose , Ditondo Juan , Losso Marcelo H. , Dolz Mariano , O’Sullivan Alexandra , Gavin Brian , Beumont-Mauviel Maria , Ca Huyen , Beci Rose , Molina Daniel , Rao Sandhya , Stock Thomas , Erhardt William , Read Sarah , Springer Jessica , Presti Rachel , Thompson Ryley , Gray Kimberly , Henry Cathy , Haile Alem , Klebert Michael , Kessels Lisa , Vehe Kathryn , Bakos Kristopher , Spitz Teresa , Hubert Sara , Alyatim Raghd , Schneider Brittany , Ayres Chapelle , Spec Andrej , Blair Laura , Afghanzada Anita , Schodl Natalie , Wahid Lana , Engemann John J. , Pinero Gloria , McLendon-Arvik Beth , Whitt Lynn , Shroba Jenny , Salsgiver Elizabeth , Alleyne Candace , Gwak Anna , Pickell Nicholas , Spagnoletti Jack , Goh Samson , Robb Katharine , Cenname Michael , Small Catherine , Plate Markus , Burgos Rodrigo , Lindsey Brenna , Herald Fischer , Echeverria Stephanie , Lewis Dorendra , Patel Mahesh , Bengtson Charles D. , Schmid Andreas , Lovell Kimberly , Lovelett Carly , Soule Daniel , Jaremczuk Daniel , Flanagan Jennie , Murray Cameron , Sands Kylie , Flint Kyle , Mohaddes Sara , Harrington Caryn , Broughal Kylie , Sogoian David , Cox Karen , Javeri Heta , Ponce Philip O. , Dixon Danielle O. , Bowling Jason E. , Patterson Jan E. , Taylor Barbara S. , Serrano Ruth C. , Sallee Kaylin , Tragus Robin , Catano Gabriel , Scholler Irma , Barajas Rose Ann , Garcia Armando , Soileau Bridgette , Heard Patricia , Camilo Endo Carvajal Manuel , Ehwarieme Rukevwe , Chandramohan Divya , Cabo Alejandro , Nawwar Abdelhameed , Quill Caroline M. , Choudhury Nayeem , Arrington Ashley , Holyfield Isaiah , Smith Abby , Brown Glenda , Varner Kyle , Baxter Joni , Roundy Tracy , Co Mary , Wessolossky Mireya , Perez-Velazquez Juan , Holter-Chakrabarty Jennifer , Karfonta Brittany , Anjum Juvaria , Marathe Jai , Castagne Myriam , Mompoint Daniel , Schroeder Ryan , Rao Mallika , Nguyen Johnathan , Plewa Jake , Donlinger Sue , Breslin Marylynn , Dodson Susan , Jenkins Mitch , Williamson John , Middleton Elizabeth A. , Tavadze Mai , Sebhatu Romai , Pierobon Jessica , Miller Nate , Lee John , Doshi Pratik , Dentino Andrew , Martin Jessica , Hinojosa Erik , Torres Pablo , Sanchez Ricardo , Murga Gladys , de la Gala Silvana , Chaiña Jhon , Ramos Jorge , Malca Jenny , Castillo Kathia , Calderon Galvez Johana , Icochea Perez Maria Lyda , Becerra Nunez Claudia Carolina , Betteta Riondato Sandra , Delgado Málaga Sandra , Barreda Sánchez Cecilia , Sánchez Morales Sylvia , Yaringano Palacios Myriam , Galarza Cuba Dora , Hermenegildo Ivan , Falla Benites Mayra , Neyra Stefania , Hernández Josefina , García Victoria , Palacios Katherine , Matos Miluska , Zuloeta Fiorella , del Carpio Fiorella , Chacaltana Gloria , de la Cruz Carmen , Ceriolli Breda Felipe , Mello Roux Leite Mauricio , Milbradt Tobias , Rodeles Luz , Benzaquen Nadia , Pezzini Sebastian , Alberdi Lucila , Serravalle Priscila , Russo Giulia , Ferini Franco , Guala Maria Eugenia , Crespo Alejandro , Benitez Agostina , Cristaldi Maria Elena , Di Renzo Paula , Gramagalia Corina , Tessini Antonela , Alonso Joana Evelin , Pic Carmen , Ceraldi Georgina , Mondino Azucena , Higareda Almaraz Iliana , Madrigal Robles Víctor Hugo , Rosas Ismerio María Fernanda , Rodarte Rodriguez Maria Fernanda , Olmos Meza Norma Esther , de la Cruz Barba Norma Esther , Alba Ponce Ana Maria , Calderon Juan Manuel , Borsetta Eduardo , Sandoval Noemí , Vazquez Daniela , Mansilla Malena , Molina Marta , Jara Yamila , De Bona Laura , Eduarda Claus Maria , Pille Arthur , Lahitte Matías , Fenés Mariángeles , Bianchi Cecilia , Miserere María Emilia , Alzogaray Maria Fernanda , Christian Sanchez Carrillo Halbert , Mano Aldana , Zuain Myrna , Toibaro Javier J. , Pachioli Valeria , Chaio Sebastián , Malamud Natalia , Bharucha David B. , Dorr Patrick , Sadeh Jonathan , Kelly Sheila , Stevens Marita , Cao Huyen , DeZure Adam , Juneja Kavita , Abdelghany Mazin , Jasion Theresa , Olson Rachel , Roebuck Megan , Huvane Jacqueline , Lindsell Christopher J. , Leimberger Jeff , Yow Eric , Huang Zhen , Kim Hwasoon , Anderson Carla , Elliott Carrie , Swartz Merri , Garg Jyotsna , Nelson Neta , Kalaria Divya , Philogene Ketty , Schulz Tim , Kuek Averie , Bah Fatou , Mitchell Jarrard , Polo Elizabeth , Wong Michelle , Baldan Sharon , Mendez Sandra , Stevens Bradford , Toledo Marcela , Abba Talita , Herrejon Emma , Gomez Cristina , Mardari Georgeta , Putta Neeraja , Mason Robin , Hamilton Holli , Eisnor Derek , O’Rourke Anna , Patel Aditi , Brody Betty , Chiang Anna , Lind Brian , Portilla Lilli M. , Gadhia Ami D. , Vepa Sury , Carlson Marti Emily , Gardner Bobbi , Rutter Joni , Schmitt Clare , Kurilla Michael 
Published: July 2023

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