Roche’s arthritis drug Actemra was one of the earliest-identified COVID-19 treatment prospects. But the latest clinical studies have yielded mixed data—and seemingly contradictory results. A large observational study that looked at 3,924 critically ill COVID-19 patients admitted to intensive care units across top U.S. institutions linked Actemra treatment to a 29% reduction in the risk of death after a median follow-up of 27 days, according to results published in JAMA Internal Medicine.
Overall, an estimated 27.5% of patients who got Actemra within two days of ICU admission would die after 30 days, versus 37.1% for those who didn’t receive it. The beneficial effect was most pronounced in patients who had a more rapid disease trajectory and were admitted to the ICU within three days of symptom onset, the study finds.
Dysregulated inflammation plays an important role in COVID-19 disease progression. As the body fights the coronavirus, it may release too many inflammatory agents that may lead to organ failure or death. IL-6, which Actemra targets, is among those molecules found to be elevated in this cytokine release syndrome.
However, controlling IL-6 with Actemra hasn’t consistently translated into clear clinical benefits as scientists had hoped.
In a randomized clinical trial of 126 severe COVID-19 patients in Italy, investigators found no evidence of an Actemra-related improvement in disease progression—namely, the lungs’ ability to exchange air, ICU admission or death, according to results also published Tuesday in JAMA Internal Medicine. Specifically, 17 patients (28.3%) in the Actemra arm and 17 (27.0%) in the standard care group showed clinical worsening in 14 days.
Then, to further complicate the situation, a randomized clinical trial, which enrolled hospitalized patients in France with moderate-to-severe COVID-19 pneumonia, also found mixed results for Actemra.
Patients on the Roche drug were 42% less likely to require ventilation or die by day 14, according to a third study that appeared Tuesday in JAMA Internal Medicine. However, on the study’s other co-primary endpoint, the drug didn’t cut the risk of disease progression to a prespecified WHO clinical status benchmark by day 4.
The three studies add to a growing body of evidence that has yet to reach a conclusion about Actemra’s role in COVID-19. They have their limitations, which makes interpreting their findings difficult. For example, there are potentially important differences in treatment groups at baseline in the U.S. observational study, Jonathan Parr of the University of North Carolina at Chapel Hill pointed out in an editorial that ran alongside the papers. Some of the patients in the Italian study who were not assigned to the experimental group actually got Actemra as their disease worsened, he noted.
He also questioned the significance of the French finding that Actemra may improve outcomes at 14 days, given mixed 28-day findings from two Roche-sponsored trials. The Covacta study showed Actemra couldn’t significantly improve clinical status or prevent death compared with placebo. But in the Empacta trial, which primarily enrolled patients from minority racial and ethnic groups, the drug led to a major reduction of mechanical ventilation or death by day 28, though the death rate difference was not statistically significant.
Parr said he would wait for detailed, peer-reviewed results from those two studies and others. The Actemra arm in the U.K.’s massive Recovery trial “will better define [Actemra’s] role in COVID-19 management,” he said. That study recently found low-cost steroid dexamethasone could reduce the death rate in hospitalized patients.
“For now, however, findings from the randomized trials described herein do not support routine [Actemra] use in COVID-19,” Parr said.