Low-dose colchicine found to be as effective as high-dose regimen for early gout flares

Low-dose oral colchicine is just as effective as high-dose colchicine in reducing pain associated with early acute gout flare, but with a safety profile statistically indistinguishable from placebo, according to a study published in the April issue of Arthritis & Rheumatism, the official journal of the American College of Rheumatology.

“High vs. Low-dosing of Oral Colchicine for Early Acute Gout Flare: Twenty-Four Hour Outcome Results of the First Randomized, Placebo-Controlled, Dose Comparison Colchicine Trial” details the AGREE (Acute Gout Flare Receiving Colchicine Evalulation) trial, a placebo-controlled comparison of low-dose and high-dose colchicine in the treatment of acute gouty flares.

“Our AGREE trial was designed to see if a lower dose of colchicine would still be effective, but with a more favorable side-effect profile,” said Matthew W. Davis, MD, RPh, chief medical officer, URL Pharma, which funded this trial.

The multicenter, randomized, double-blind, placebo-controlled, parallel-group study evaluated the safety and efficacy of low-dose versus high-dose colchicine in male and postmenopausal female patients aged ≥18 years with a confirmed past diagnosis of gout and ≥2 gout flares within the prior 12 months. A stable regimen of urate-lowering therapy was permitted. A total of 575 patients were randomly assigned into one of three treatment groups: 1) a novel “low-dose” (1.8 mg over 5 hours) abbreviated colchicine regimen group; 2) a “high-dose” (4.8 mg over 6 hours) colchicine regimen group that reflects long-standing medical practice and is still actively taught to physicians; 3) placebo. Of these patients, 185 had an acute gout flare; 184 were included in the efficacy analysis. The primary end point was ≥50% pain reduction at 24 hours without rescue medication.

Both low-dose colchicine and high-dose colchicine were superior to placebo and had equivalent efficacy, according to the study results.“The surprise of the study was that the adverse event profile of the low-dose colchicine was similar to the placebo arm,” Dr Davis said.One out of 5 patients in the high-dose colchicine group had severe intensity adverse events, including severe diarrhea; 1 of 6 in this group also experienced vomiting. None of the patients in the low-dose colchicine group experienced either severe adverse events or vomiting.“In conclusion, the results of the AGREE trial provide the first evidence basis, after centuries of colchicine use, for low-dose colchicine therapy in the treatment of early acute gout flare,” Dr Davis said. “The low-dose colchicine regimen maintained efficacy equivalent to that of high-dose colchicine. It had a side-effect profile significantly better than that of high-dose colchicine and comparable with that of placebo. The results…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.”

Prior to AGREE, only one other placebo-controlled study evaluated colchicine for the treatment of acute gout flare, a 43-patient trial by Ahern from 1987. In this trial, all the subjects who were taking colchicine had gastrointestinal toxicity (diarrhea). “The Ahern trial showed that high-dose colchicine was effective, but with a high price in [terms of] side effects,” Dr Davis said.

According to Dr Davis, primary care physicians see approximately 98% of all gout patients; rheumatologists treat approximately 2%.