Severely ill COVID-19 patients were less likely to die in the hospital if they took a drug used to treat rheumatoid arthritis, according to doctors from Greensboro-based Cone Health.
Doctors at Cone hospitals described their findings on use of the drug tocilizumab in a research paper on the website medRxiv, which posts research findings before they are certified by outside experts and formally published. The FDA has approved tocilizumab for Phase Three clinical trials as a COVID-19 treatment.
Though the Cone study posted Tuesday showed benefits, a study by UNC researchers and medical students urged caution. The drug did not have clear benefits for patients at UNC, researchers said in a paper posted on the site on the same day.
Dr. Jonathan Parr, an assistant professor at the UNC School of Medicine, said doctors at the UNC Medical Center decided to cut back on using the drug after results showed their patients were not seeing the benefits reported in studies in France and China.
“It made us rethink our use of the drug,” said Parr, one of the UNC paper’s authors. “Much of the medical literature we’re using to base our clinical decisions on is rapidly evolving. All of us clinicians are hungry for evidence to guide our decision making. What we really need are randomized controlled trials.”
The Cone study looked at the drug’s effectiveness: “Do our patients benefit in a real-world setting?” Monica Schmidt, a senior data scientist at Cone Health and one of that paper’s authors, said in an interview Wednesday.
“One of the things that was really striking is these were the sickest patients and it still had benefits,” she said.
Hard to compare studies
In an email to The News & Observer, Schmidt said it was difficult to compare the Cone and UNC findings because UNC did not have a “control arm,” or a group of patients not given the drug to use as a comparison.
“UNC-Chapel Hill released more of a case report that looked at only treated patients,” she said. “Without a group to compare, it is difficult to ascertain the survival benefits. Without a control arm, it is impossible to compare to our findings.”
Parr agreed that the two studies could not be compared because they use different approaches. ”The two studies have very different designs,” he said.
Still, the conclusions of these two studies are different, with the Cone researchers reporting their study “demonstrates the potential effectiveness of Tocilizumab in a real-world setting for treatment of hospitalized patients with severe and life threatening COVID-19 disease,” while the UNC report says “our findings raise questions about its use in critically ill patients.”
The Cone study
In some COVID-19 patients, the virus triggers a “cytokine storm” where the immune system runs wild and causes severe lung damage. Tocilizumab is used to dampen the cytokine storm.
Dr. Murali Ramaswamy, a pulmonary and critical care specialist at LeBauer Healthcare at Cone Health, said doctors were told how to prescribe the drug if they thought their patients would benefit. A team including pharmacists, critical care, infectious disease, and in-patient treatment specialists developed the protocol.
Studies out of China, including one by researchers at Anhui Provincial Hospital and the Institute of Immunology and the Chinese Academy of Sciences, indicated tocilizumab was effective.
The Cone study included 86 patients; 21 got the drug and 65 didn’t.
The decision to take the drug was left up to doctors and patients, said Ramaswamy, who analyzed the data and is one of the paper’s authors.
“Many got it because they were the sickest,” he said.
Three patients who took tocilizumab died, while eight patients who didn’t take it died. The actual mortality rates for patients who took the drug are about the same, but researchers used statistical models to show that patients treated with the drug had a reduced risk of dying in the hospital.
The UNC study
The UNC study, which looked at records from 11 patients, said the drug did “not provide clear evidence of clinical improvement.”
Clinicians at UNC decided with each patient how to use the drug, Parr said.
The UNC researchers wrote that UNC Medical Center patients may have done worse than patients in China because the UNC patients were more seriously ill. Nine of the 11 patients in the UNC study were men. Five were Latino, three were African American, and three were white. Six patients were obese and eight had high blood pressure. People who are obese or have high blood pressure are at risk of getting severe cases of COVID-19.
“I think all of us are looking for a silver bullet in the treatment of COVID-19, especially in the the treatment of severe disease,” Parr said in an interview Wednesday. “In our patients at UNC, tocilizumab was not the silver bullet.”
In the Cone Health study, 11 of the 21 patients who got tocilizumab were white, seven were African American, and three are classified as “other.” They had an average body mass index in the obese range, and three had a history of high blood pressure.