It has long been understood that COVID-19 causes an extreme inflammatory response, dysregulating cytokine and chemokine networks. Despite significant advances in anti-inflammatory treatments, there are still significant morbidities and mortalities among COVID-19 patients.

A new study, published in JAMA, sought to evaluate multiple immune modulators plus standard care in patients hospitalized with COVID-19. “Medications disrupting IL-6 signaling (tocilizumab) and the Janus kinase pathway (baricitinib) show benefit in the most severely ill patients with COVID-19,” the study authors explained.

The randomized, double-blind, placebo-controlled study examined whether abatacept, cenicriviroc, or infliximab benefitted COVID-19 pneumonia patients. Abatacept is a T-cell costimulatory modulator that mitigates T-cell responses, cenicriviroc is a CCR2/CCR5 antagonist that reduces monocyte and macrophage functions while sparing neutrophil and T-cell function, and infliximab is a tumor necrosis factor α (TNF) inhibitor that binds and neutralizes soluble and transmembrane TNF.

From October 16, 2020–December 31, 2021, 1971 participants were recruited from 95 hospitals. Included participants were 18 years or older with a confirmed COVID-19 diagnosis within 14 days, an anticipated hospital stay of 72 hours or more, and evidence of pulmonary involvement. Patients were randomized to study drug or placebo, additionally receiving standard care, including remdesivir and corticosteroids.

The study drug cohorts received either abatacept (10 mg/kg; maximum dose, 1000 mg), infliximab (5 mg/kg), or cenicriviroc (300-mg loading dose followed by 150 mg twice daily). While the former 2 immunomodulators were given as a single infusion, cenicriviroc was an oral medication administered for 28 days.

The 1971 randomized participants averaged 54.8 years of age and 61.8% male. Compared to placebo, 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).

All-cause 28-day mortality was 11.0% for abtacept (15.1% for placebo), 13.8% for cenicriviroc (11.9% for placebo), and 10.1% for infliximab (14.5% for placebo). In all 3 substudies, safety outcomes were comparable between active treatment and placebo, including for secondary infections.

The investigators found that time to recovery from COVID-19 pneumonia among hospitalized patients was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. None of the immunomodulators reached a statistically significant primary endpoint.

In light of these results, the study authors emphasized the need to continue evaluating treatments that may reduce COVID-19 morbidity and mortality. “Expanding treatment armament available globally and developing optimized treatment strategies remains paramount,” they concluded.

Source link