Adverse events during oral colchicine use: a systematic review and meta-analysis of randomised controlled trials

Abstract

Background: Colchicine is a widely used drug to treat inflammatory diseases. Due to its long historical use in medicine, controlled clinical trials have been small and there remains some caution with the use of this drug in patients with co-morbidities. The aim of the study is to systematically examine the side effect profile of colchicine in controlled clinical trials across all published indications. Methods: A systematic review was conducted in accordance with PRISMA methodology. The Cochrane Library, MEDLINE and EMBASE were searched for double-blind controlled trials of oral colchicine in adult patients that reported adverse event data. Meta-analyses were used to determine the relative risk (RR) of adverse events in colchicine users compared to comparator groups. Results: A total of 4915 studies were initially identified and after exclusions, 35 randomised controlled trials with placebo (n = 30) or active comparators (n = 5) were included. The most common diseases studied were gout, liver cirrhosis and pericarditis. There were a total of 8659 pooled participants, 4225 participants were randomised to receive colchicine, 3956 to placebo and 411 to an active comparator. Diarrhoea was reported in 17.9% of colchicine users versus 13.1% in comparator groups (RR 2.4, 95% confidence interval (CI) 1.6, 3.7). Any gastrointestinal event was reported in 17.6% of colchicine users and 13.1% of comparators (RR 1.7, 95% CI 1.3, 2.3). Adverse liver events were reported in 1.9% of colchicine users versus 1.1% in the comparator groups (RR 1.6, 95% CI 0.9, 3.0). Muscle events were reported in 4.2% of colchicine users and 3.3% in the comparator groups (RR 1.3, 95% CI 0.8, 1.9). Haematology events were reported in 0.6% of colchicine users and 0.4% of comparator groups (RR 1.34 (0.64, 2.82). No study reported neuropathy events. Other sensory events were reported in 1.1% of colchicine users and 1.5% of comparator groups (RR 1.4, 95% CI 0.3, 6.7). Infectious events were reported in 0.4% of colchicine users and 2.1% of comparator groups (RR 1.0, 95% CI 0.7, 1.5). No study reported death as an adverse event. Conclusion: Colchicine increases the rate of diarrhoea and gastrointestinal adverse events but does not increase the rate of liver, sensory, muscle, infectious or haematology adverse events or death.

Combined Use of Febuxostat and Colchicine Does Not Increase Acute Hepatotoxicity in Patients with Gout: A Retrospective Study

“…Guo X. et al reported that CYP3A inhibition was associated with colchicineinduced hepatotoxicity in animals [28]. However, a meta-analysis study demonstrated that adverse liver events did not increase in gout patients with colchicine use [29]. The present study also revealed that the number of patients with hepatotoxicity was not significantly higher in colchicine users than non-users.…”

Wedelolactone facilitates Ser/Thr phosphorylation of NLRP3 dependent on PKA signalling to block inflammasome activation and pyroptosis

“…Once colchicine is long-term used, it often brings side effects such as liver and kidney injury and gastrointestinal reactions. 42 Importantly, we have demonstrated that wedelolactone indeed suppressed caspase 1 (p20) and IL-1β expression in MSU-induced gouty arthritis. As wedelolactone might inhibit both the genes expression and the inflammasome activation in vivo to reduce the production of inflammatory cytokine, we mainly focused on the anti-inflammasome mechanism of wedelolactone, and MSU-induced inflammation was partly conducted to verify its role in inhibiting NLRP3 activation in vivo.…”

Association between treatment with colchicine and improved survival in a single-centre cohort of adult hospitalised patients with COVID-19 pneumonia and acute respiratory distress syndrome

“…Diarrhoea occurred in 7.4% of treated patients, which is in line with data reported in the systematic review of the literature. 13 The main finding of this study was that patients treated with colchicine had a better survival rate as compared with SoC. We acknowledge that this result might be affected by a survival bias deriving from the inclusion in the colchicine group of patients who were 'survivors' at the moment of initiating the treatment with this drug.…”

“…12 The side effect profile of colchicine is widely known, with gastrointestinal symptoms occurring in up to 17% of patients, while severe organ manifestations being rare. 13 Based on the identification of HIS in patients with COVID-19 pneumonia and the anti-inflammatory properties of colchicine, we postulated the rationale of use of colchicine in patients admitted to the hospital for COVID-19.…”