Colchicine for Gout Gets a Clean Bill of Health

Colchicine, a first-line treatment option for acute gout, is associated with an increased risk of adverse events, such as diarrhea and other gastrointestinal symptoms, but not serious adverse events, finds a newly published systematic review and meta-analysis.

Colchicine is an oral anti-inflammatory that was approved by the U.S. Food and Drug Administration in 1961. It is also used to treat Behcet's Syndrome and Familial Mediterranean Fever. Since colchicine has been used as an anti-inflammatory treatment for decades, there is little new research documenting adverse events. In this systematic review, which was published in a February issue of Arthritis Research & Therapy by Philip C. Robinson, MB.Ch.B., Ph.D., University of Queensland, Australia, researchers set out to document adverse events for high risk groups―such as those with kidney and liver impairment, patients taking higher doses of colchicine, or patients who may be taking CYP3A4 inhibitors. 

How this age-old treatment controls inflammation is not quite fully understood, but Dalbeth N. et al. writing in Clinical Therapeutics (Oct. 1, 2014), described a few possible pathways.

“Colchicine modulates multiple pro- and anti-inflammatory pathways associated with gouty arthritis. Colchicine prevents microtubule assembly and thereby disrupts inflammasome activation, microtubule-based inflammatory cell chemotaxis, generation of leukotrienes and cytokines, and phagocytosis. Many of these cellular processes can be found in other diseases involving chronic inflammation. The multimodal mechanism of action of colchicine suggests potential efficacy of colchicine in other comorbid conditions associated with gout, such as osteoarthritis and cardiovascular disease,” according to Dalbeth N., et al.

While adverse events associated with colchicine use have been reported in some clinical trials, they have not been studied systematically.

“The mechanism by which colchicine induces diarrhea and other gastrointestinal symptoms is not exactly known but can be attributed to an increase in prostaglandin synthesis, intestinal secretion and gastrointestinal motility with this drug. Although these symptoms can be clinical features of colchicine toxicity, they are usually mild, short-lived and reversible with dose reduction,” the authors wrote.

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The review included 35 randomized controlled trials with placebo or active comparators, none of which reported serious adverse events, such as neuropathy, myotoxicity or death. It examined the side effect profile of colchicine  across all published indications. A total 8,659 participants were included, of which 4,225 received colchicine, 3,956 received placebo and 411 received an active comparator, such as piroxicam, cyclosporin, and prednisolone. The most common diseases studied were gout, liver cirrhosis and pericarditis.

Diarrhea was reported in 17.9 percent of colchicine users versus 13.1 percent in comparator groups (relative risk [RR] 2.4, 95% confidence interval (CI) 1.6, 3.7). The reported rate of any gastrointestinal event was 17.6 percent and 13.1 percent (RR 1.7, 95% CI 1.3, 2.3), respectively.

“While these are not benign side effects in some individuals, they will settle on dose reduction or drug discontinuation,” the authors wrote.

For colchicine users and comparator groups, the respective reported rates of adverse liver events were 1.9 percent and 1.1 percent (RR 1.6, 95% CI 0.9, 3.0), muscle events were 4.2 percent and 3.3 percent (RR 1.3, 95% CI 0.8, 1.9), and hematology events were 0.6 percent and 0.4 percent (RR 1.34, 95% CI 0.64, 2.82).

While no neuropathy events were reported, other sensory events were reported in 1.1 percent of colchicine users and 1.5 percent of comparator groups (RR 1.4, 95% CI 0.3, 6.7). The respective infectious events rates were 0.4 percent and 2.1 percent (RR 1.0, 95% CI 0.7, 1.5). No deaths were reported.

REFERENCE

Sarah Stewart, Kevin Chih Kai Yang, Kate Atkins, et al. “Adverse events during oral colchicine use: a systematic review and meta-analysis of randomised controlled trials.”Arthritis Research & Therapy. February 13, 2020. https://doi.org/10.1186/s13075-020-2120-7