Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized with COVID-19 Pneumonia: A Randomized Clinical Trial

O'Halloran J.A.; Ko E.R.; Anstrom K.J.; Kedar E.; McCarthy M.W.; Panettieri R.A., Jr; Maillo M.; Nunez P.S.; Lachiewicz A.M.; Gonzalez C.; Smith P.B.; De Tai S.M.-T.; Khan A.; Lora A.J.M.; Salathe M.; Capo G.; Gonzalez D.R.; Patterson T.F.; Palma C.; Ariza H.; Lima M.P.; Blamoun J.; Nannini E.C.; Sprinz E.; Mykietiuk A.; Alicic R.; Rauseo A.M.; Wolfe C.R.; Witting B.; Wang J.P.; Parra-Rodriguez L.; Der T.; Willsey K.; Wen J.; Silverstein A.; O'Brien S.M.; Al-Khalidi H.R.; Maldonado M.A.; Melsheimer R.; Ferguson W.G.; McNulty S.E.; Zakroysky P.; Halabi S.; Benjamin D.K., Jr; Butler S.; Atkinson J.C.; Adam S.J.; Chang S.; Lavange L.; Proschan M.; Bozzette S.A.; Powderly W.G. · JAMA (2023) · DOI: 10.1001/jama.2023.11043

Resumen

Importance: Immune dysregulation contributes to poorer outcomes in COVID-19. Objective: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. Design, Setting, and Participants: Randomized, 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. Interventions: Single 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 Measures: The 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. Results: Of 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 Relevance: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT04593940.