Can we still consider treatment with colchicine effective in SARS-COV-2 infection? Systematic review, meta-analysis, and trial sequential analysis

Abstract

OBJECTIVE: To assess the effectiveness of colchicine, compared with standard of care, for reducing mortality, admission to intensive care, and use of mechanical ventilation. MATERIALS AND METHODS: We performed a systematic review, meta-analysis, and sequential trial analysis. The terms (SARS-CoV-2 OR COVID-19 OR coronavirus) AND (colchicine) were searched in MEDLINE, Scopus, Embase, Cochrane Central Register of Controlled Trials, and preprint repositories (February 2020 to April 2021, extended to June 2021). Risk of bias for randomised controlled trials and observational studies were assessed using the tools RoB 2.0 and ROBINS-I, respectively. We performed subgroup analyses based on study design and sensitivity analyses based on time of colchicine administration. RESULTS: We included six observational studies (1329 patients) and five clinical trials (16,048 patients). All studies but one were conducted in the hospital setting. Colchicine treatment was not associated with a significant decrease in mortality (RR 0.93, 95% CI 0.87 to 1; p=0.06, I2=72%) with a significant subgroup effect (p<0.001) depending on the design of the studies. The drug was effective in observational studies (RR 0.57, 95% CI 0.46 to 0.70, p<0.001, I2=50%) but not in clinical trials (RR 0.99, 95% CI 0.92 to 1.07, p=0.89, I2=21%). The effect of colchicine on intensive care admissions and the need for mechanical ventilation could not be confirmed. Trial sequential boundaries for cumulative meta-analyses of randomised controlled trials suggested no significant effect on mortality (p=0.182) beyond the optimal information size (13,107 patients). CONCLUSIONS: Our results suggest that colchicine treatment has no effect on mortality in hospitalised patients with SARS-CoV-2 infection, and that no further confirmatory clinical trials are needed owing to futility.