Should colchicine be used to treat acute gout?
Low-quality evidence shows that low-dose colchicine (up to 1.8 mg over one hour) is an effective therapy for acute gout. However, it has not been compared with nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids in clinical trials. Concerns include high cost, drug-drug interactions, and potential toxicity. (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)
Colchicine is an alkaloid inhibitor of microtubule formation derived from the meadow saffron or autumn crocus in the Northern Hemisphere. It has been used since ancient times for medicinal purposes. In 2009, after sponsoring a small randomized controlled trial, URL Pharma received exclusive rights to produce colchicine (Colcrys) for gout and the much rarer disease, familial Mediterranean fever. As a result, the price increased 50-fold from about $0.10 to $5.00 per pill.1
This Cochrane review updates a 2006 meta-analysis of a single study of 43 people. A second industry-sponsored study of 185 people was added to the current review. Both were randomized controlled trials. In the more recent study, the authors compared a high-dose colchicine regimen to a low-dose regimen. The high-dose regimens in the two studies—which included a 1- to 1.2-mg loading dose, followed by either 0.6 mg every hour for six hours or 0.5 mg every two hours until therapeutic response or intolerance (i.e., nausea, vomiting, or diarrhea)—caused significantly more adverse effects (number needed to treat to harm = 2). The shorter, low-dose regimen of 1.2 mg, followed by 0.6 mg in one hour (followed by placebo every hour for five hours) was as effective as the higher dosages in the more recent study, but with adverse effects similar to those in the placebo group. Using an outcome of at least 50% pain reduction at 24 to 32 hours with low-dose colchicine vs. placebo, the number needed to treat for the low-dose regimen was five.
No trials compared colchicine with other interventions (e.g., NSAIDs, corticosteroids). Most participants in these two studies were men, and this Cochrane review does not address whether colchicine is beneficial after the first two days of an exacerbation.
The 2012 American College of Rheumatology guidelines for managing gout state that low-dose colchicine is equal to NSAIDs and corticosteroids for treating acute gout.2 For severe acute gout, colchicine may be used with NSAIDs or corticosteroids. The guidelines call for at least six months of anti-inflammatory prophylaxis while starting urate-lowering therapy to prevent gout flare-ups, and slightly favor colchicine in a dosage of 0.6 mg once to twice daily in this regard.
The dose of colchicine should be reduced for patients with severe renal or hepatic disease. There is a 1% risk of reversible axonal neuromyopathy in patients taking colchicine; colchicine can cause rhabdomyolysis when used with statins or clarithromycin (Biaxin); and colchicine has multiple drug-drug interactions with cytochrome P3A4 inhibitors, including certain antiviral agents, antifungal agents, calcium channel blockers, and grapefruit.3,4 Comparative studies among the different treatments for acute gout and for flare-up prophylaxis are needed.