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Low-Dose Colchicine Effective for Acute Gout Flare-ups



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Am Fam Physician. 2011 Feb 1;83(3):316.

Background: Although colchicine is commonly used to treat gout, dosing regimens have not been well studied. One randomized placebo-controlled trial reported that a mean dose of 6.7 mg (initially 1 mg orally, followed by 0.5 mg every two hours until relief or an adverse event occurred) improved pain within 48 hours, with diarrhea affecting all participants. Severe adverse events and death have occurred when colchicine is combined with P-glycoprotein and cytochrome P450 3A4 inhibitors (e.g., clarithromycin [Biaxin], erythromycin, cyclosporine [Sandimmune]). Low-dose colchicine regimens have never been fully evaluated. Terkeltaub and colleagues compared low- and high-dose colchicine with placebo in the treatment of gout flare-ups.

The Study: The AGREE (Acute Gout Flare Receiving Colchicine Evaluation) trial randomized 575 men and postmenopausal women to receive one of three treatments: low-dose colchicine (1.2 mg, followed by 0.6 mg one hour later [1.8 mg total]), high-dose colchicine (1.2 mg, followed by 0.6 mg every hour for six hours [4.8 mg total]), or placebo. Patients started the study medication within 12 hours of an acute gout flare-up and were monitored for adverse events (e.g., diarrhea). Simultaneous urate-lowering therapy was permitted. The primary end point was at least a 50 percent reduction in pain within 24 hours of the first dose without the need for a rescue medication.

Results: Overall, 185 patients had a gout flare-up during the study: 52 in the high-dose group, 74 in the low-dose group, and 59 in the placebo group. Less than one-third of patients were receiving concurrent urate-lowering therapy. Both high- and low-dose colchicine regimens were significantly more effective than placebo at relieving pain (32.7, 37.8, and 15.5 percent, respectively). Diarrhea was the most common adverse event, and was significantly more common in persons in the high-dose group compared with the other groups (see accompanying table). Adverse event rates were similar between the low-dose colchicine and placebo groups.

Table.

Risk of Adverse Events with High- vs. Low-Dose Colchicine for Gout Flare-ups

Adverse event Treatment group Odds ratio
High-dose colchicine (%) Low-dose colchicine (%) Placebo (%) High- vs. low-dose colchicine Low-dose colchicine vs. placebo High-dose colchicine vs. placebo

Diarrhea

76.9

23.0

13.6

11.2

1.9*

21.3

Nausea

17.3

4.1

5.1

5.0

0.8*

3.9*

Vomiting

17.3

0

0

Serious adverse events‡

0

0

0


*—Not significant.

—Not calculable.

—For example, a life-threatening adverse event, need for hospitalization, or death.

Table.   Risk of Adverse Events with High- vs. Low-Dose Colchicine for Gout Flare-ups

View Table

Table.

Risk of Adverse Events with High- vs. Low-Dose Colchicine for Gout Flare-ups

Adverse event Treatment group Odds ratio
High-dose colchicine (%) Low-dose colchicine (%) Placebo (%) High- vs. low-dose colchicine Low-dose colchicine vs. placebo High-dose colchicine vs. placebo

Diarrhea

76.9

23.0

13.6

11.2

1.9*

21.3

Nausea

17.3

4.1

5.1

5.0

0.8*

3.9*

Vomiting

17.3

0

0

Serious adverse events‡

0

0

0


*—Not significant.

—Not calculable.

—For example, a life-threatening adverse event, need for hospitalization, or death.

Conclusion: Low-dose colchicine is as effective as the more traditional high-dose regimen in alleviating acute gout flare-ups, with an adverse event profile similar to placebo. The authors recommend an immediate change in clinical practice to use the low-dose regimen, which is consistent with recent expert opinion–based recommendations by the European League Against Rheumatism.

Source

Terkeltaub RA, et al. High versus low dosing of oral colchicine for early acute gout flare: twenty-four–hour outcome of the first multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison colchicine study. Arthritis Rheum. April 2010;62(4):1060–1068.


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