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Adding colchicine (Colcrys) to current standard of care COVID treatment was not associated with any benefit, but it was associated with more adverse events, a meta-analysis found.

In a pooled analysis involving six intention-to-treat studies, colchicine as an "add-on" COVID-19 treatment was not significantly associated with a reduced risk of mortality (risk difference 0.00, 95% CI -0.01 to 0.01), mechanical ventilation (risk ratio [RR] 0.67, 95% CI 0.38-1.21), or ICU admission (RR 0.49, 95% CI 0.19-1.25) versus standard treatments alone, reported Kedar Gautambhai Mehta, MD, MBBS, of GMERS Medical College Gotri in Gujarat, India, and colleagues.

Colchicine was also not associated with a decreased risk of serious adverse events (risk difference -0.01, 95% CI -0.02 to 0.00), shorter length of hospital stay (mean difference -1.17 days, 95% CI -3.02 to 0.67), but was associated with a higher risk of any adverse event (RR 1.58, 95% CI 1.07-2.33), including diarrhea specifically (RR 1.93, 95% CI 1.62-2.29), the authors wrote in .

"Although colchicine has proved effective for various chronic inflammatory conditions, its non-beneficial effect in COVID-19 has been linked to its effect on intracellular pH," they explained. "The effect of colchicine on intracellular pH is dynamic with a net result being that it fails to raise intracellular pH to a level that prevents virus from binding to ACE2."

Colchicine has been used for decades, and was more recently granted in 2009 to treat acute gout flares and familial Mediterranean fever. Early data on the drug for COVID seemed promising in both hospitalized patients and early in disease course. However, Mehta and colleagues noted conflicting trial data, including from the large-scale trial (included in the present analysis), which found no mortality benefit or reduced need for mechanical ventilation with colchicine for hospitalized COVID-19 patients.

Mehta's group evaluated data from six randomized controlled trials (RCTs) involving 16,148 COVID-19 patients to investigate the safety and efficacy of colchicine as an "add-on" or concomitant treatment. Blinded or open-label RCTs involved inpatients or outpatients of any age who had laboratory-confirmed COVID-19 and received colchicine compared to another intervention (placebo, best supportive care). Relevant studies had more than 10 participants in all treatment arms.

All six RCTs examined mortality, five also looked at ventilation, four studied length of hospital stay, and three looked at ICU admission, diarrhea, adverse events, and serious adverse events.

The analysis had several limitations, and the researchers acknowledged that the findings were based on "moderate quality evidence." Database searches for relevant trials were restricted to include only those with free, open access. The analysis was also based on a small number of studies, a few of which were open-label trials.

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