In the first COVID-19 case series of tocilizumab in the United States, UNC-Chapel Hill researchers report sobering results. They say the drug should be used judiciously until randomized clinical trials determine tocilizumab’s true efficacy.
Meanwhile, medical students sidelined from clinical rotations by the virus conducted the research with lightning speed, all virtually.
In the ongoing battle against COVID-19, tocilizumab is one of the drugs doctors have turned to for treating severely ill patients. For the first time in the United States, UNC researchers report that the drug did not show clear benefit to 11 severely ill patients and should be used with caution. Their findings, published preliminarily at medRxiv.org, suggest the dire need for detailed data from large randomized clinical trials of tocilizumab and other potential treatments.
“We all want a silver bullet solution for COVID-19, especially for our most critically ill patients,” says senior author Jonathan Parr, MD, assistant professor of infectious diseases at UNC. “Tocilizumab dramatically reduces select inflammatory markers, but it remains unclear whether its activity leads to equally dramatic effects on clinical outcomes, especially in critically ill patients.”
Tocilizumab is typically used to treat autoimmune diseases such as rheumatoid arthritis and lupus. Essentially, the drug fights against the body’s overaggressive inflammatory response, which is partly driven by increased levels of IL-6. When doctors in China noticed that severely ill COVID-19 patients had high IL-6 levels, they gave them tocilizumab and reported promising results in two small groups of patients. A report from France described similar promising results. Doctors at UNC Medical Center began using the drug for some of their most severely ill COVID-19 patients, but they weren’t seeing the same positive effect.
In April, weeks after being sent home from campus, three students from the UNC School of Medicine and Gillings School of Global Public Health found their way to Parr, who co-directs the medical center’s COVID-19 infectious diseases inpatient unit, looking to help. Students have not been allowed on clinical wards since March, so Parr suggested they could help with research. Co-first authors Casey Rimland and Camille Morgan, both fourth-year MD-PhD students, and doctoral student Griffin Bell extracted and analyzed a month’s worth of data from patients treated with tocilizumab at UNC.
“These three students pulled off a pretty incredible feat in a short period of time,” Parr says. “In less than three weeks, they evaluated all of our tocilizumab-treated patients, analyzed the data, presented it to the pulmonary/critical care and infectious diseases divisions, and then we submitted the paper for publication. They really seized the moment to make a big difference.”
Rimland says working with Parr and her fellow students was a great antidote to having her clinical rotations cancelled this spring and being sent home.
“It was really nice to finally feel like we were doing something useful and to be able to put my PhD and medical school training to use,” says Rimland, who otherwise was staying busy by teaching herself to crochet and helping with childcare for UNC employees. “We all just said ‘Let’s go, let’s get this done.’”
Working completely online and talking by phone and Zoom calls, the students divided up the patients and reviewed their charts, each bringing different skill sets to the work. “Jonathan was very collaborative. He trusted us to do the right thing, but he gave us direction and responded quickly if we needed it,” she says. “It was nice to experience a collaborative scientific undertaking, that doesn’t always happen.”
Of the 11 patients at UNC Medical Center, nine were critically ill, requiring mechanical ventilation in an intensive care unit at the time of tocilizumab administration. In contrast to the earlier studies, the UNC researchers did not observe significant clinical improvement in temperature or oxygen requirements in most patients, in contrast to previous studies. During the UNC study, two patients were discharged, five remained in critical condition in the intensive care unit, one was weaned off the ventilator, and three died.
Parr said the results suggest the drug might have a benefit to some patients, but more studies are needed so that doctors know which patients are most likely to benefit from tocilizumab, which is expensive and difficult to procure.
“The patients we treated were very sick, sicker than in other studies,” Parr says. “This might be the main reason why our findings are different than prior studies. Also, our patients had co-morbidities; they provided a more accurate snapshot of the patient population we care for in North Carolina. Unfortunately, we did not observe clear clinical improvements in two major indicators – fever reduction and oxygen level improvement” — two areas where previous studies reported clinical improvement.
“What this says to us is, whenever possible, we want to prioritize getting patients into randomized controlled trials. This will allow us to answer these difficult questions about which treatments work best for which patients.”
Adapted from a story by Mark Derewicz for UNC Health and School of Medicine.