TY - JOUR
T1 - Abatacept for Treatment of Adults Hospitalized with Moderate or Severe Covid-19
AU - ACTIV-1 IM study group members
AU - Ko, Emily R
AU - Anstrom, Kevin J
AU - Panettieri, Reynold A
AU - Lachiewicz, Anne M
AU - Maillo, Martin
AU - O'Halloran, Jane A
AU - Boucher, Cynthia
AU - Smith, P Brian
AU - McCarthy, Matthew W
AU - Segura Nunez, Patricia
AU - Mendivil Tuchia de Tai, Sabina
AU - Khan, Akram
AU - Mena Lora, Alfredo J
AU - Salathe, Matthias
AU - Kedar, Eyal
AU - Capo, Gerardo
AU - Rodríguez Gonzalez, Daniel
AU - Patterson, Thomas F
AU - Palma, Christopher
AU - Ariza, Horacio
AU - Patelli Lima, Maria
AU - Blamoun, John
AU - Nannini, Esteban C
AU - Sprinz, Eduardo
AU - Mykietiuk, Analia
AU - Wang, Jennifer P
AU - Parra-Rodriguez, Luis
AU - Der, Tatyana
AU - Willsey, Kate
AU - Benjamin, Daniel K
AU - Wen, Jun
AU - Zakroysky, Pearl
AU - Halabi, Susan
AU - Silverstein, Adam
AU - McNulty, Steven E
AU - O'Brien, Sean M
AU - Al-Khalidi, Hussein R
AU - Butler, Sandra
AU - Atkinson, Jane
AU - Adam, Stacey J
AU - Chang, Soju
AU - Maldonado, Michael A
AU - Proscham, Michael
AU - LaVange, Lisa
AU - Bozzette, Samuel A
AU - Powderly, William G
PY - 2022/9/26
Y1 - 2022/9/26
N2 - BACKGROUND: We investigated whether abatacept, a selective costimulation modulator, provides additional benefit when added to standard-of-care for patients hospitalized with Covid-19.METHODS: We conducted a master protocol to investigate immunomodulators for potential benefit treating patients hospitalized with Covid-19 and report results for abatacept. Intravenous abatacept (one-time dose 10 mg/kg, maximum dose 1000 mg) plus standard of care (SOC) was compared with shared placebo plus SOC. Primary outcome was time-to-recovery by day 28. Key secondary endpoints included 28-day mortality.RESULTS: Between October 16, 2020 and December 31, 2021, a total of 1019 participants received study treatment (509 abatacept; 510 shared placebo), constituting the modified intention-to-treat cohort. Participants had a mean age 54.8 (SD 14.6) years, 60.5% were male, 44.2% Hispanic/Latino and 13.7% Black. No statistically significant difference for the primary endpoint of time-to-recovery was found with a recovery-rate-ratio of 1.14 (95% CI 1.00-1.29; p=0.057) compared with placebo. We observed a substantial improvement in 28-day all-cause mortality with abatacept versus placebo (11.0% vs. 15.1%; odds ratio [OR] 0.62 [95% CI 0.41- 0.94]), leading to 38% lower odds of dying. Improvement in mortality occurred for participants requiring oxygen/noninvasive ventilation at randomization. Subgroup analysis identified the strongest effect in those with baseline C-reactive protein >75mg/L. We found no statistically significant differences in adverse events, with safety composite index slightly favoring abatacept. Rates of secondary infections were similar (16.1% for abatacept; 14.3% for placebo).CONCLUSIONS: Addition of single-dose intravenous abatacept to standard-of-care demonstrated no statistically significant change in time-to-recovery, but improved 28-day mortality.TRIAL REGISTRATION: ClinicalTrials.gov ( NCT04593940 ).
AB - BACKGROUND: We investigated whether abatacept, a selective costimulation modulator, provides additional benefit when added to standard-of-care for patients hospitalized with Covid-19.METHODS: We conducted a master protocol to investigate immunomodulators for potential benefit treating patients hospitalized with Covid-19 and report results for abatacept. Intravenous abatacept (one-time dose 10 mg/kg, maximum dose 1000 mg) plus standard of care (SOC) was compared with shared placebo plus SOC. Primary outcome was time-to-recovery by day 28. Key secondary endpoints included 28-day mortality.RESULTS: Between October 16, 2020 and December 31, 2021, a total of 1019 participants received study treatment (509 abatacept; 510 shared placebo), constituting the modified intention-to-treat cohort. Participants had a mean age 54.8 (SD 14.6) years, 60.5% were male, 44.2% Hispanic/Latino and 13.7% Black. No statistically significant difference for the primary endpoint of time-to-recovery was found with a recovery-rate-ratio of 1.14 (95% CI 1.00-1.29; p=0.057) compared with placebo. We observed a substantial improvement in 28-day all-cause mortality with abatacept versus placebo (11.0% vs. 15.1%; odds ratio [OR] 0.62 [95% CI 0.41- 0.94]), leading to 38% lower odds of dying. Improvement in mortality occurred for participants requiring oxygen/noninvasive ventilation at randomization. Subgroup analysis identified the strongest effect in those with baseline C-reactive protein >75mg/L. We found no statistically significant differences in adverse events, with safety composite index slightly favoring abatacept. Rates of secondary infections were similar (16.1% for abatacept; 14.3% for placebo).CONCLUSIONS: Addition of single-dose intravenous abatacept to standard-of-care demonstrated no statistically significant change in time-to-recovery, but improved 28-day mortality.TRIAL REGISTRATION: ClinicalTrials.gov ( NCT04593940 ).
U2 - 10.1101/2022.09.22.22280247
DO - 10.1101/2022.09.22.22280247
M3 - Article
C2 - 36203544
JO - medRxiv : the preprint server for health sciences
JF - medRxiv : the preprint server for health sciences
ER -