Colchicine for the prevention of COVID-19 "hard" outcomes: All that glitters is not gold.

Dear Editor,

In a paper recently published in the European Journal of Internal Medicine, Schattner provided a thorough and in-depth review regarding the multiple, pleiotropic effects of colchicine, also highlighting its potential beneficial effects in coronavirus disease 2019 (COVID-19) [1]. In their commentary, Kow et al. [2] emphasize on the need for further trials with a longer treatment duration for the assessment of colchicine's therapeutic efficacy, dampening the initial enthusiasm. Previous meta-analyses of observational studies and randomized controlled trials demonstrated a mortality benefit with colchicine in patients with COVID-19, leading to the amendment of treatment protocols against the disease worldwide [3,4].

Upon the recent publication of further randomized controlled trials, we sought to determine whether colchicine compared to standard of care offers a true benefit, both in the in-hospital and out of hospital setting, for the prevention of surrogate COVID-19 outcomes. We searched PubMed and Cochrane Library databases for relevant published randomized controlled trials up to 12th November 2021. We set as primary efficacy outcome the surrogate endpoint of COVID-19 death and as secondary efficacy outcome that of mechanical ventilation. We extracted the data from the eligible reports, by using a pilot tested, data extraction form.

As we assessed only dichotomous variables, differences were calculated with the use of risk ratios (RR), with 95% confidence interval (CI), after implementation of the Mantel-Haenszel (M-H) random effects formula. Statistical heterogeneity among studies was assessed by using I2 statistics. All analyses were performed at the 0.05 significance level, while they were undertaken with RevMan 5.3 software.

We finally included 6 randomized controlled trials [5], [6], [7], [8], [9], [10] in at total of 15,624 subjects with documented COVID-19 infection. All trials except for one [8] enrolled hospitalized patients. As shown in Fig. 1 , colchicine was not superior to standard of care in terms of prevention of COVID-19 death (RR = 0.63, 95% CI; 0.33 – 1.20, I2 = 28%). In addition, colchicine did not result in a significant decrease in the risk for mechanical ventilation during disease course (RR = 0.66, 95% CI; 0.36 – 1.20, I2 = 48%), as shown in Fig. 2 .

Fig. 1

Effect of colchicine compared to control on the risk for COVID-19 death.

Fig. 2

Effect of colchicine compared to control on the risk for mechanical ventilation due to COVID-19.

The present pooled analysis of relevant, published randomized controlled trials so far does not support the routine use of colchicine for the prevention of surrogate COVID-19 outcomes in daily clinical practice, either in the in-hospital or in the community therapeutic management of patients with COVID-19. Whether colchicine can positively affect the prognosis of COVID-19 in specific patients’ populations, such as those suffering from autoinflammatory diseases [11], has to be further confirmed in randomized controlled trials, besides hypothesis-generating observational studies.

Funding

None.

Acknowledgments

None.

Declaration of Competing Interest

None declared.