As the understanding of COVID-19 has evolved and the medical community has developed an appreciation for the role of cytokine overproduction in negative COVID-19 outcomes, rheumatologists and cardiologists around the world have asked: “Can we tap the brakes before things get bad?”
Dr. Pillinger says he and his colleagues designed this study to answer that question. Other studies have examined the treatment’s ability to help non-hospitalized patients with COVID-19. The first studies were small. Individual hospitals around the world tried colchicine, and the results were consistently positive.5 They found colchicine was helpful in reducing hospital stays and mortality, if given on the first day or two of arrival.
For this larger study, physicians around the world came together to create a phase 3, randomized double-blind, adaptive, placebo-controlled, multi-center clinical trial. Dr. Pillinger and his colleague in the U.S., Binita Shah, MD, a cardiologist at NYU, were among these physicians. Thus, he found himself not only at the epicenter of the U.S. pandemic, but also leading the U.S. arm of the international study.
Dr. Pillinger was pleased with the study results. “When we ran it through, it cut admissions by 25%. The higher the risk the patient, the more [colchicine] seemed to be effective,” he says.
Barriers to Adoption
“It’s not very sexy,” says Dr. Pillinger, noting colchicine is inexpensive—the poor cousin in a rheumatologist’s arsenal of expensive biologic drugs. The colchicine story was also not helped by the intense—and ultimately unsatisfying—focus on hydroxychloroquine (HCQ) in early 2020.
“The whole world got burned over the [HCQ] story,” says Dr. Pillinger, referencing how early in the pandemic U.S. President Donald Trump identified HCQ as a cure for COVID-19. Ultimately, however, the scientific data did not support this early claim. “The idea that another very old, pre-existing rheumatologic drug may be effective raised some skepticism.”
Dr. Pillinger also notes the COLCORONA study was different from most COVID-19 studies. “We were focused on outpatient [treatment], and everyone else was focused on inpatient,” he says.
The colchicine outpatient message was buried by data from the RECOVERY trial in the U.K. That study found that patients with COVID-19 who were receiving invasive mechanical ventilation or oxygen alone who were treated with dexamethasone experienced a lower 28-day mortality rate than those treated with placebo.6 The study continued by randomizing patients to receive other treatments, including REGN-COV2, a combination of two monoclonal antibodies directed against the SARS-CoV-2 spike protein; aspirin; colchicine; or usual care alone, which may include a glucocorticoid, macrolide antibiotic, HCQ, lopinavir/ritonavir or IL-6 antagonist. The colchicine arm was stopped because preliminary analysis revealed no significant difference in the primary endpoint for the 28-day mortality rate.
