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.
Author(s): Terkeltaub RA, Furst DE, Bennett K, Kook KA, Crockett RS, Davis MW.
Affiliation(s): VAMC San Diego, and University of California, San Diego, CA 92161, USA.
rterkeltaub@ucsd.edu
Publication date & source: 2010, Arthritis Rheum. , 62(4):1060-8
OBJECTIVE: 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.
METHODS: 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 > or = 50% pain reduction at 24 hours without rescue
medication.
RESULTS: 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.
CONCLUSION: 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.
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