Rheumatoid arthritis drug falls short as treatment for hospitalized Covid-19 patients in three studies

Tocilizumab, a repurposed rheumatoid arthritis drug once considered a promising treatment for hospitalized patients with Covid-19, generally did not increase patients’ chances of survival or help them get better faster, according to three trials published this week.

However, a fourth trial did find the drug increased the chances of survival, but because it was an observational study, the results are considered less definitive.

Three of the trials were published Tuesday in the Journal of the American Medical Association and the other was published Wednesday in the New England Journal of Medicine.

While this leaves the picture for tocilizumab use a bit muddy, the studies taken together show the drug isn’t a magic bullet that should be used in all hospitalized patients with Covid-19, but they leave the door open for possible use in specific patient groups.

“It is possible that forthcoming results from other randomized trials will help us identify specific groups of people who will benefit. However, growing evidence supports current guidelines, which recommend against tocilizumab use outside of clinical trials,” Dr. Jonathan Parr told CNN.

Parr, an assistant professor in the division of infectious diseases at the University of North Carolina at Chapel Hill, wrote an editorial that was published alongside the three studies in JAMA.

Tocilizumab, sold under the brand name Actemra and used to treat rheumatoid arthritis, blocks interleukin-6, a molecule that produces inflammation.

Earlier in the pandemic, the drug became widely used in the United States after reports from China and Europe appeared to show it helped very ill patients who experienced a so-called cytokine storm by extinguishing the out-of-control inflammation that developed in response to the coronavirus.

Study results start coming in

However, those early reports were mostly observational, meaning they took existing data and analyzed it as opposed to designing a trial specifically to assess tocilizumab.

But now the results from trials designed to look at the drug prospectively are beginning to come in.

The first of the three JAMA studies found that hospitalized patients in Italy who were not yet in intensive care and who received tocilizumab fared no better than those who received standard care. The trial was stopped early due to “futility.”

A similar study in France found that tocilizumab may have led to slight improvements by day 14 over usual care, but there were no differences in survival by day 28.

The third study found that the risk of in-hospital death was about 30% lower in US patients receiving tocilizumab within the first two days of ICU admission compared to those who didn’t get the drug.

But because it was an observational trial there could be factors that affected the results other than how well the drug itself worked.

“We specifically studied tocilizumab administration in very sick patients, all of whom required ICU level of care. In contrast, the [other two trials] studied patients with much milder illness severity,” said Dr. Shruti Gupta of Brigham and Women’s Hospital in Boston, who led the study team.

Dr. David Leaf, the trial’s senior author, added, “We focused on early use of tocilizumab — within the first two days of ICU admission. This may be the key to tocilizumab’s efficacy — administering it prior to the occurrence of irreversible organ injury,” he said in an email.

Gupta said their findings need confirmation by a large randomized, controlled trial.

The fourth study, published Wednesday in the New England Journal of Medicine, used the gold standard of trial design– it’s a randomized, double-blind, placebo control trial.

It enrolled 243 patients from seven Boston-area hospitals who were admitted with Covid-19 at the height of the surge in that region.

“The primary goal of the trial was to determine if tocilizumab, administered intravenously at a moderate stage of the patients’ disease, could prevent progression to intubation or death,” said Dr. John H. Stone, lead study author and director of Clinical Rheumatology at Massachusetts General Hospital, told CNN via email.

But the findings were not encouraging for the use of tocilizumab.

“Our data do not support the concept that early IL-6 receptor blockade is an effective treatment strategy in moderately ill patients hospitalized with Covid-19 infection,” said Stone.

Results show that the chances of intubation or death were about similar in both groups and patients in both groups essentially took the same amount of time to discontinue supplemental oxygen.

So, where does that leave tocilizumab?

“Tocilizumab may still have a role in COVID-19. Several large trials are expected to come out soon that will tell us more about how and when it should be used, if at all,” said Parr, noting that it “shouldn’t be taken off the table completely, but we need more convincing evidence before using it routinely.”

Stone agreed that the drug may still benefit other patient groups, but he stressed the importance of doing these trials.

“An important take-away point from our trial and the overall experience with IL-6 receptor blockade is that any such approach to the treatment of COVID-19 must be subjected to randomized, blinded trials,” he said, adding that the trials should be done “before the adoption of widespread use.”


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