As a more detailed picture comes to light of the effects of SARS-CoV-2, the virus that causes COVID-19, investigators are finding increasing evidence of systemic inflammation. While antiviral medications such as remdesivir take aim at the virus itself, other therapeutic strategies may be needed to keep inflammation in check.
When a colleague approached infectious disease specialist Ann Woolley, MD, about a randomized, controlled clinical trial to use tocilizumab as an anti-inflammatory drug for COVID-19 patients early in disease, Woolley immediately recognized the medication. Tocilizumab, which is a monoclonal antibody that blocks the inflammatory protein IL-6, is currently approved to treat giant cell arteritis, rheumatoid arthritis and other arthritic diseases. It is also administered to cancer patients who have received chimeric-antigen receptor therapy (CAR-T), a treatment that can stoke the body’s immune system to attack cancer cells but can also cause toxic side effects due to cytokine release syndrome — an overwhelming inflammatory response that can cause multiple organ failure. As an infectious disease specialist, Woolley consults on cancer patients receiving tocilizumab when there’s a concern that a patient may be predisposed to infection.
Woolley now serves as the Brigham’s site principal investigator for the COVID-19 trial of tocilizumab along with Sarah Nikiforow, MD, PhD, a hematologist and oncologist. Many of the collaborators involved in the work are the same colleagues she has consulted with for cases long before the pandemic.
“This study is a collaboration across centers and across specialties,” Woolley said. “Infectious disease specialists are involved, but so are oncologists, cardiologists, and rheumatologists who are deeply familiar with the drug. Management of COVID-19 patients requires integration across disciplines and a variety of expertise.”
John Stone, MD, a rheumatologist at Mass General, serves as the principal investigator for the study, which is a phase 3, randomized, double-blind placebo-controlled clinical trial. Genentech, which manufactures tocilizumab, is sponsoring the investigator-led trial. Participants are randomized 2:1 to receive tocilizumab or a placebo and will be followed for 28 days after receiving their last dose. The primary endpoint of the study is time to mechanical ventilation or death. The trial completed enrollment of close to 300 patients in June. Results are expected this fall.
In addition to Mass General and the Brigham, sites for the study include Newton Wellesley, North Shore Medical Center, Lahey, Boston Medical Center and St. Elizabeth’s Hospital — many of which cared for large numbers of patients with COVID-19 during the surge.
“This has been such a great example of partnership among hospitals in an effort to make advanced care through clinical trials available to more patients,” said Woolley.