Colchicine May Improve Clinical Outcomes in COVID-19 Patients, Further Research Needed

Arthritis drugs seem to be dominating the headlines in terms of clinical trials for COVID-19. One of the recent randomized, clinical trials analyzed the effect of colchicine, compared to standard care, on cardiac and inflammatory biomarkers, as well as clinical outcomes, in hospitalized COVID-19 patients. While the anti-inflammatory drug did not largely affect the biomarkers, it appeared to improve clinical outcomes, according to the Greek Study in the Effects of Colchicine in COVID-19 Complications Prevention (GRECCO-19) randomized clinical trial. The authors of this study noted that the difference was “based on a narrow margin of clinical significance” and recommended that the findings of the study be used to guide hypotheses for future research. Colchicine is prescribed to treat patients with gout and rheumatic disease, with previous studies observing its favorable safety-benefit profile in patients who also have cardiovascular disease. “The anti-inflammatory action of colchicine is mediated by completely different pathophysiologic routes than that of corticosteroids and nonsteroidal anti-inflammatory agents. In addition, colchicine inhibits neutrophil chemotaxis and activity in response to vascular injury, inhibits inflammasome signaling and reduces the production of active interleukin-1β, reduces neutrophil-platelet interaction and aggregation, and has rapid onset of anti-inflammatory effects when the standard oral regimen of colchicine used for gout flares (1.2 mg initially followed by 0.6 mg every hour for 6 hours or until severe gastrointestinal symptoms occur) is followed,” the study authors explained.

Colchicine vs. Standard Treatment

In GRECCO-19, which took place at 16 tertiary hospitals in Greece, 105 hospitalized COVID-19 patients were randomized 1:1 from April 3 through April 27 to either colchicine plus standard care or standard care alone. The treatment group received a 1.5-mg loading dose of colchicine followed by 0.5 mg after 60 minutes and maintenance doses of 0.5 mg twice daily. Treatment was administered for up to three weeks. The primary endpoints were:
  • maximum high-sensitivity cardiac troponin level
  • time for C-reactive protein (CRP) to reach >3 times the upper reference limit
  • time to deterioration by two points on a seven-grade clinical status scale (scale ranged from able to resume normal activities to death)
Additional outcomes were:
  • percentage of patients requiring mechanical ventilation
  • all-cause mortality
  • number, type, severity, and seriousness of adverse events (AEs)
Among the total cohort, 61 patients (58.1%) were male, and the median age was 64 years; 55 patients (52.4%) were randomized to the treatment group and 50 (47.6%) to the control group. The median peak high-sensitivity cardiac troponin value was 0.008 in the treatment group versus 0.0112 ng/mL in the control group; median CRP levels were 3.1 mg/dL and 4.5 mg/dL, respectively. In the colchicine group, 1.8% of patients (n=1/55) achieved the clinical primary endpoint, compared to 14.0% (n=7/50) of the control patients. The mean event-free survival time was slightly longer in the colchicine group than the control group (20.7 days vs. 18.6 days). AEs did not largely differ between the groups, except that the colchicine group had a higher rate of diarrhea than the control group (45.5% vs. 18.0%). The results of the GRECCO-19 trial were published in JAMA Network Open, with the study authors concluding, “In this randomized clinical trial, participants who received colchicine had statistically significant improved time to clinical deterioration compared with a control group that did not receive colchicine. However, the observed difference was based on a narrow margin of clinical significance; therefore, these observations should be considered hypothesis generating.”