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

Authors

  • Robert A. Terkeltaub,

    Corresponding author
    1. VAMC San Diego, and University of California, San Diego
    • VA Medical Center, Rheumatology 111K, 3350 La Jolla Village Drive, San Diego, CA 92161
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    • 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).

  • Daniel E. Furst,

    1. University of California, Los Angeles
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    • Dr. Furst has received consulting fees from Abbott, Actelion, Amgen, Bristol-Myers Squibb, Biogen Idec, Centocor, Gilead, Genentech, GlaxoSmithKline, Merck, Nitec, Novartis, UCB, Wyeth, and Xoma (less than $10,000 each), speaking fees from Abbott, Actelion, and UCB (less than $10,000 each), and honoraria from Abbott, Actelion, Amgen, Bristol-Myers Squibb, Biogen Idec, Centocor, Genentech, Gilead, Merck, and Nitec (less than $10,000 each); he has received grants from Abbott, Actelion, Amgen, Bristol-Myers Squibb, Genentech, Gilead, GlaxoSmithKline, the NIH, Nitec, Novartis, Roche, UCB, Wyeth, and Xoma. Salamandra, LLC (employer of Drs. Bennett and Kook) is a regulatory and clinical consulting firm contracted by URL Pharma. D.A.T.A. Inc. (employer of Dr. Crockett) is a contract statistics company retained by United Biosource (a contract research organization) to provide statistical services for this clinical trial.

  • Katherine Bennett,

    1. Salamandra, LLC, Bethesda, Maryland
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  • Karin A. Kook,

    1. Salamandra, LLC, Bethesda, Maryland
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  • R. S. Crockett,

    1. D.A.T.A. Inc., Bayou La Batre, Alabama
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  • Matthew W. Davis

    1. URL Pharma, Inc., Philadelphia, Pennsylvania
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    • Dr. Davis owns stock options in URL Pharma, and he holds 2 patents pertaining to the dosing of colchicine with clarithromycin.


  • ClinicalTrials.gov identifier: NCT00506883.

Abstract

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 ≥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.

Ancillary