Neither abatacept, cenicriviroc, nor infliximab improved time to recovery from COVID-19 pneumonia in hospitalized patients, according to study findings published in the Journal of the American Medical Association.
Researchers aimed to determine if patients hospitalized with COVID-19 pneumonia received benefit from adding immunomodulators (abatacept, cenicriviroc, or infliximab) to standard care. Time to recovery by day 28 was the primary endpoint.
Study authors reported on findings of a randomized, double-blind, placebo-controlled clinical trial (ClinicalTrials.gov Identifier: NCT04593940) that used the National Institutes of Health Accelerating COVID-19 Therapeutic Interventions and Vaccines Immune Modulator master protocol (ACTIV-1 IM) to evaluate 3 immunomodulatory agents (abatacept, cenicriviroc, or infliximab) used in patients hospitalized with moderate/severe COVID-19. The trial enrolled adult patients from mid-October 2020 through December 2021 who had confirmed SARS-CoV-2 infection within the preceding 14 days and evidence of pulmonary involvement.
The current analysis used results of 3 sub-studies from 95 hospitals and 85 clinical research sites in the US and Latin America to assess immunomodulators added to standard care to treat patients hospitalized with COVID-19 pneumonia. A total of 1971 patients (mean 54.8 years of age; 38.2% women) were assigned to 1 of the 3 immunomodulatory agents or to a placebo cohort for 1 of the 3 agents. In the intervention groups, patients received either single infusion abatacept (10mg/kg; maximum dose, 1000 mg) or infliximab (5mg/kg), or they received a 28-day oral course of cenicriviroc (300 mg loading dose followed by 150 mg twice daily). All patients also received standard care, which included corticosteroids and remdesivir.
Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo.
Time to recovery by day 28 was assessed using an 8-point ordinal scale, with higher scores were indicative of better health. The first day the patient scored at least 6 on the ordinal scale was used to define recovery.
Investigators found that no statistically significant difference in time to recovery between the intervention agent vs placebo for abatacept (recovery rate ratio [RRR], 1.12; 95% CI, 0.98-1.28; P =.09; median time to recovery, 9 days for abatacept and placebo); cenicriviroc (RRR,1.01; 95% CI, 0.86-1.18; P =.94; median time to recovery, 8 days for intention-to-treat population), or infliximab (RRR, 1.12; 95% CI, 0.99-1.28; P =.08; median time to recovery, 8 days for intention-to-treat population).
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); 10.1% for infliximab vs 14.5% for placebo (OR, 0.59; 95% CI, 0.39-0.90) (all in the treated-as-assigned population).
Safety outcomes, including secondary infections in all 3 sub-studies, were comparable between treatment groups and placebo.
Study limitations include lack of data on patient vaccination status and possible lack of adherence in cenicriviroc oral medication twice daily.
Study authors said, “The ACTIV-1 IM master protocol evaluated the benefit of an additional immunomodulator added to standard care in hospitalized participants with moderate to severe COVID-19 pneumonia.” Investigators concluded, “Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.