Colchicine: A potential outpatient treatment for PCR-confirmed COVID-19?

The use of the anti-inflammatory drug colchicine in an outpatient setting may reduce the risk of COVID-19–related death or hospitalization in patients with PCR-confirmed COVID-19, according to results of the phase III COLCORONA* trial.

“[T]he risk of ... death or hospital admission due to COVID-19 infection in the 30 days following randomization was not statistically significantly lower among the patients who were randomly assigned to receive colchicine than in those who received placebo,” said the authors.

“[However,] when the patients who had a confirmed diagnosis of COVID-19 are considered, the benefit of colchicine on the primary-efficacy endpoint was more marked and statistically significant,” they said.

Participants in this multinational, double-blind trial were 4,488 patients aged ≥40 years (median age 54 years, 53.9 percent female) with ≥1 high-risk characteristic and not hospitalized due to PCR-diagnosed or presence of clinical criteria for COVID-19 in the past 24 hours. They were randomized 1:1 to receive oral colchicine (0.5 mg BID for 3 days followed by QD for the next 27 days) or placebo.

Patients were enrolled a mean 5.3 days after symptom onset. About 20 percent of patients had diabetes and mean BMI was 30 kg/m². They received study treatment for a mean 26.2 days.

The overall incidence of death or hospitalization for COVID-19 at 30 days post-randomization was lower among patients who received colchicine compared with placebo, though the results were not statistically significant (4.7 percent vs 5.8 percent; odds ratio [OR], 0.79, 95.1 percent confidence interval [CI], 0.61–1.03; p=0.081). [Lancet Respir Med 2021;9:924-932]

However, a prespecified analysis showed that the incidence of death or hospitalization for COVID-19 was significantly lower in the colchicine vs placebo group when restricted to the 4,159 patients (93 percent) with PCR-confirmed COVID-19 (4.6 percent vs 6.0 percent; OR, 0.75, 95.1 percent CI, 0.57–0.99; p=0.042).

In those with PCR-confirmed COVID-19, the primary outcome events mainly consisted of hospitalization for COVID-19 (4.5 percent vs 5.9 percent; OR, 0.75), with death occurring in 0.2 and 0.4 percent, respectively (n=5 vs 9; OR, 0.56). A post hoc analysis also showed that patients in the colchicine group were less likely to require mechanical ventilation than those in the placebo group (0.5 percent vs 1.0 percent; OR, 0.50).

The results were consistent across multiple subgroups including history of diabetes, hypertension, and cardiovascular or respiratory disease, age (≥70 and <70 years), race, BMI (≥30 and <30 kg/m²), and use of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers.

The number needed to treat with colchicine to prevent one primary endpoint event was 70 in patients with PCR-proven COVID-19, 29 in those with diabetes, 31 in those aged ≥70 years, 39 in men, 52 in patients with respiratory disease, and 25 in those with cardiovascular disease.

Treatment-related adverse events occurred in 24.2 and 15.5 percent of colchicine and placebo recipients, respectively, and serious AEs in 4.9 and 6.3 percent, respectively.

The lower incidence of serious AEs with colchicine vs placebo may “reflect the benefits of systemic-inflammation reduction in this disease,” noted the authors.

Fewer colchicine than placebo recipients experienced pneumonia (2.9 percent vs 4.1 percent; p=0.021), though treatment-emergent gastrointestinal events (23.9 percent vs 14.8 percent) and diarrhoea (13.7 percent vs 7.3 percent; p<0.0001) were more common with colchicine than placebo. All incidents of pulmonary embolism (affecting 0.5 percent of colchicine and 0.1 percent of placebo recipients) were considered unrelated to the study medication and did not warrant mechanical ventilation or lead to death. There were no incidents of deep vein thrombosis. Three and six patients in the colchicine and placebo group, respectively, experienced dehydration.

Is there a role for colchicine?

“Prevention of COVID-19 complications in an outpatient setting ideally requires a clinically approved, orally administered, and inexpensive medication targeting the inflammasome with a known favourable safety profile,” said the authors.

“Given the absence of orally administered therapies to prevent COVID-19 complications in community-treated patients, the burden on healthcare systems caused by hospital admissions, and the benefit of colchicine in patients with PCR-proven COVID-19, we propose that colchicine is a safe and inexpensive anti-inflammatory agent that could be considered for use in those at risk of complications,” they said. They recommended that efforts be made to replicate the findings in other studies of PCR-positive community-treated patients.

The authors noted that the positive outcomes were specific to patients with confirmed COVID-19 diagnosis with a risk of complications and that the long-term impact of colchicine remains unknown.

In addition, older age and male sex carry an increased mortality risk in patients hospitalized for COVID-19, suggesting that the present cohort “cannot be considered to be in the highest-risk category,” remarked Dr Clark Russell from the University of Edinburgh Centre for Inflammation Research, Edinburgh, UK, in a commentary. [Lancet Respir Med 2021;9:811-812]

Further research in higher-risk patients may be necessary, particularly closer to symptom onset and with a higher dose of colchicine, he recommended.