According to the results of a dose-comparison trial, a low-dose of oral colchicine given over one hour offers comparable efficacy and better tolerability than the more common high-dose regimen given over six hours in acute gout.

The authors note that high-dose (or prolonged) colchicine regimens are commonly described, despite a high risk:benefit ratio.  Lower dose regimens have been suggested but never rigorously studied, therefore the AGREE (Acute Gout Flare Receiving Colchicine Evaluation) study was conducted.  Prior to this a pharmacokinetic study was conducted, which found that the two regimens (see below) produced similar peak blood colchicine concentrations. 

The trial included 575 adults with a confirmed past diagnosis of gout and ≥2 gout flares within the prior 12 months, who were randomised to self-administered double-blind treatment with one of the following when they had an acute gout flare (to start within 12 hours of symptom onset):

• "low-dose" colchicine (1.2 mg followed by 0.6 mg in 1 hour followed by placebo doses every hour for 5 hours [1.8 mg total]) -  the novel regimen
• "high-dose" colchicine (1.2 mg followed by 0.6 mg every hour for 6 hours [4.8 mg total]) – selected to mimic common practice
• placebo (two placebo capsules initially, followed by one placebo capsule every hour for 6 hours) 

Rescue medication was permitted if intolerable pain continued after taking at least one dose of the study drug; uric acid lowering therapy was not to be discontinued at the onset of flare.  Patients rated intensity of joint pain on the 11-point Likert scale (range from that ranged from 0-10); the primary endpoint was the proportion of patients who were responders ( 50% pain reduction at 24 hours without rescue medication). The primary analysis compared the proportion of responders in the high-dose colchicine and placebo groups [the study does not appear to have been powered to compare the response rates for the low-dose and high-dose groups).

Of the 575 patients randomised into the trial, 185 had an eligible gout flare and took study medication, including high-dose colchicine (n=52), low-dose colchicine (n=74) and placebo (n=59).  The majority were middle-aged overweight white men with a high serum urate level and a 10-year history of gout.  The main findings included:

• The response rates were 37.8% (28/74) in the low-dose group, 32.7% (17/52) in the high-dose group and 15.5% (9/58) in the placebo group (p = 0.005 for low-dose versus placebo and p=0.034 for high-dose versus placebo).

• Rescue medication was taken within the first 24 hours by 31.1% (p=0.027), 34.6% (p=0.103), and 50.0%, respectively.

• Low-dose colchicine had a similar adverse events (AEs) profile as placebo (OR 1.5, 95% CI 0.7 - 3.2). However the high-dose regimen was associated with a higher frequency of AEs than low-dose regimen or placebo, including diarrhoea (76.9% of the high-dose, 23.0% of the low-dose, and 13.6% of the placebo groups) and vomiting (17.3% of the high-dose group; not reported in the other groups). 

The authors conclude, based on the results of the pharmacokinetic and AGREE studies, that achieving a peak blood colchicine level of approximately 6mg/L provides significant reduction in pain associated with early gout flare, and that increasing total colchicine exposure by giving doses higher than 1.8mg over 1 hour may lead to increased side effects without additional clinical benefit.  They note that their results are consistent with recent EULAR recommendations, and support an immediate change in clinical practice from a high-dose colchicine regimen to a low-dose colchicine regimen for treatment of early gout flare.