Anti-Inflammatory Agents May Have Role in COVID-19 Pneumonia

WASHINGTON -- Use of the anti-inflammatory agents infliximab (Remicade) and abatacept (Orencia) added to standard of care showed a hint of improvement in outcomes for patients hospitalized with COVID-19 pneumonia, according to results from the ACTIV-1 IM trial.

Compared with a median time to recovery of 9 days with placebo, it was 8 days with infliximab (OR 1.13, 95% CI 0.99-1.29, P=0.063) and 9 days with abatacept (OR 1.14, 95% CI 1.00-1.29, P=0.057), reported Emily Ko, MD, PhD, of Duke University Health System in Durham, North Carolina, during her late-breaking presentation at IDWeek.

"The primary endpoint of time to recovery did not meet statistical significance," Ko said, "but there was a trend toward improvement."

A key secondary outcome, mortality at day 28, occurred in 10.1% of infliximab patients compared with 14.5% of placebo patients (OR 0.59, 95% CI 0.39-0.90), and in 11% of abatacept patients versus 15.1% of placebo patients (OR 0.62, 95% CI 0.41-0.94).

"We found substantial benefit of 28-day all-cause mortality for both infliximab and abatacept," Ko noted. "Our findings show similar results compared to other immunomodulators. Baricitinib [Olumiant] and tocilizumab [Actemra] each demonstrated about a 4% absolute reduction in 28-day mortality when added to standard of care."

Mortality at day 60 also favored infliximab (12.6% vs 16.5% with placebo; OR 0.68, 95% CI 0.46-1.00), although this analysis was part of the safety data and was not a key secondary endpoint. The same was true for abatacept (14.5% vs 17.1% with placebo; OR 0.74, 95% CI 0.50-1.08).

Patients on low-flow oxygen and those with higher levels of C-reactive protein appeared to benefit more from treatment with the immunomodulators, she added.

"These were interesting results," session co-moderator Adarsh Bhimraj, MD, of Houston Methodist, told MedPage Today. "We have data of benefit with dexamethasone and IL-6 inhibitors, so now it is good to see that other parts of the inflammatory cascade also have a similar effect on COVID-19."

"I think that future studies should include combinations of these treatments once people are not responding to dexamethasone," he added. "We should also explore if there are clinical phenotypes or biomarkers such as C-reactive protein levels that can predict patients who might benefit from drugs such as abatacept or infliximab."

Patients were enrolled in ACTIV-1 IM if they had been hospitalized or were waiting for admission in the emergency department with symptoms of COVID-19, and subsequently diagnosed through laboratory testing, as well as one of the following: radiographic infiltrates by imaging, oxygen levels of 94% or less on room air, need for supplemental oxygen, or need for mechanical ventilation or extracorporeal membrane oxygenation.

For the part of the study that compared infliximab to placebo, Ko and colleagues assigned 517 patients to infliximab and 516 patients to placebo. For the abatacept comparison, they assigned 509 patients to abatacept and 510 patients to placebo. In both study arms, mean age was approximately 55 years, 62-65% were white, and 63% of the active arms were men versus 58% in the placebo arms.

At baseline, patients reported experiencing symptoms for about 9 days before going to the hospital. More than half of the patients in both arms of the trial had obesity, more than 25% had diabetes, and 40-42% had hypertension.

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