RA Biologics Lower COVID-19 Deaths, but Not Recovery Time Save

Do abatacept, cenicriviroc, or infliximab improve time to recovery for patients hospitalized with COVID-19 pneumonia compared with standard care?

Findings  A randomized, double-masked, placebo-controlled master protocol clinical trial found that treatment with abatacept ABA), cenicriviroc, or infliximab (INFLX) showed no statistically significant difference for the primary end point of time to recovery in patients with COVID-19 pneumonia vs standard care. Cenicriviroc is an oral, dual chemokine (CCR2 and CCR5) antagonist.

Meaning  Abatacept, cenicriviroc, or infliximab did not decrease time to recovery for hospitalized patients with COVID-19 pneumonia.

The NIH sponsored, ACTIV-1 Immune Modulator (IM) trial was developed to compare multiple drugs at once in hospitalized patients with COVID-19 pneumonia. They studied if adding anti-inflammatory drugs — infliximab, abatacept or cenicriviroc — to standard care would improve outcomes over standard of care alone. Standard care for such patients includes remdesivir, an antiviral drug, and dexamethasone, a corticosteroid.

This multicenter, multinational trial recruited adults with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement and were randomized to either a 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). The primary outcome was time to recovery by day 28.

The study included 1971 COVID-19 patients with a mean age of 55 years and 62% were men.

The time to recovery from COVID-19 pneumonia (primary end point) was not significantly different (compared with placebo):

• 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)
• infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) .

However, all-cause 28-day mortality was significantly lower in patients treated with ABA and INFLX:

• ABA mortality 11.0% vs 15.1% for placebo (OR 0.62 [95% CI, 0.41-0.94])
• Cenicriviroc mortality 13.8% vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94])
• INFLX mortality 10.1% 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.

While time to recovery was unaffected, 28 day mortality rates from COVID-19 pneumonia were significantly lower for abatacept and infliximab vs placebo.