Dr. Terkeltaub has received consulting fees from Altus, Ardea, BioCryst, Novartis, Pfizer, Procter & Gamble, Regeneron, Savient, EnzymeRx, Takeda, URL Pharma, and UCB (less than $10,000 each) and has received Research Service grants from the VA (more than $10,000).
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†
Article first published online: 21 JAN 2010
Copyright © 2010 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 62, Issue 4, pages 1060–1068, April 2010
How to Cite
Terkeltaub, R. A., Furst, D. E., Bennett, K., Kook, K. A., Crockett, R. S. and Davis, M. W. (2010), 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 & Rheumatism, 62: 1060–1068. doi: 10.1002/art.27327
ClinicalTrials.gov identifier: NCT00506883.
- Issue published online: 30 MAR 2010
- Article first published online: 21 JAN 2010
- Accepted manuscript online: 21 JAN 2010 12:00AM EST
- Manuscript Accepted: 21 DEC 2009
- Manuscript Received: 24 JUN 2009
- URL Pharma
Despite widespread use of colchicine, the evidence basis for oral colchicine therapy and dosing in acute gout remains limited. The aim of this trial was to compare low-dose colchicine (abbreviated at 1 hour) and high-dose colchicine (prolonged over 6 hours) with placebo in gout flare, using regimens producing comparable maximum plasma concentrations in healthy volunteers.
This multicenter, randomized, double-blind, placebo-controlled, parallel-group study compared self-administered low-dose colchicine (1.8 mg total over 1 hour) and high-dose colchicine (4.8 mg total over 6 hours) with placebo. The primary end point was ≥50% pain reduction at 24 hours without rescue medication.
There were 184 patients in the intent-to-treat analysis. Responders included 28 of 74 patients (37.8%) in the low-dose group, 17 of 52 patients (32.7%) in the high-dose group, and 9 of 58 patients (15.5%) in the placebo group (P = 0.005 and P = 0.034, respectively, versus placebo). Rescue medication was taken within the first 24 hours by 23 patients (31.1%) in the low-dose group (P = 0.027 versus placebo), 18 patients (34.6%) in the high-dose group (P = 0.103 versus placebo), and 29 patients (50.0%) in the placebo group. The low-dose group had an adverse event (AE) profile similar to that of the placebo group, with an odds ratio (OR) of 1.5 (95% confidence interval [95% CI] 0.7–3.2). High-dose colchicine was associated with significantly more diarrhea, vomiting, and other AEs compared with low-dose colchicine or placebo. With high-dose colchicine, 40 patients (76.9%) had diarrhea (OR 21.3 [95% CI 7.9–56.9]), 10 (19.2%) had severe diarrhea, and 9 (17.3%) had vomiting. With low-dose colchicine, 23.0% of the patients had diarrhea (OR 1.9 [95% CI 0.8–4.8]), none had severe diarrhea, and none had vomiting.
Low-dose colchicine yielded both maximum plasma concentration and early gout flare efficacy comparable with that of high-dose colchicine, with a safety profile indistinguishable from that of placebo.