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

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, doubleblind, 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-totreat 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, ClinicalTrials.gov identifier: NCT00506883.

Reductions in Use of Colchicine after FDA Enforcement of Market Exclusivity in a Commercially Insured Population

“…The dependent variable was a binary indicator for receiving colchicine within 30 days after diagnosis, and independent variables were constructed based on the month of diagnosis in order to estimate the linear trend in the log odds of receiving colchicine, separately from January 2009 to September 2010 and from January 2011 to December 2012, as shown in the model, Logit{Pr(Y i =1)}=b 0 + b 1 T 1i +b 2 T 2i +b 3 Post i , where Y is the indicator of colchicine dispensing, T 1 is a time variable that represents when each patient was diagnosed with gout as the number of months after January 2009, T 2 is a time spline that begins in January 2011, and Post is a binary indicator of being diagnosed in January 2011 or after. The 90-day skip period corresponds to the transition time provided in the FDA's order enforcing Colcrys' market exclusivity.…”

“…3 The trial randomized 184 patients to receiving placebo (n=58), a low-dose colchicine regimen (n=74) that had been recommended by professional society treatment guidelines, 4 and a high-dose regimen (n=52). After 1 week, gout patients in the low-dose regimen reported good symptom management and fewer adverse events than the longer regimen.…”

Are Dosing Adjustments Required for Colchicine in the Elderly Compared with Younger Patients?

“…All subjects provided written informed consent before study participation, which was conducted in accordance with the US Code of reported in the US prescribing information [4], reviews [5,9], and studies in young subjects [10,11], but the potential effect of age per se on drug disposition of this formulation has not been formally investigated until now. The objective of this study was to compare the pharmacokinetics of colchicine following the oral administration of a single 0.6 mg tablet of the approved colchicine formulation when given to young (18-30 years of age) and elderly (≥60 years of age) healthy subjects following an overnight fast.…”

Patient awareness, knowledge and use of colchicine: an exploratory qualitative study in the Counties Manukau region, Auckland, New Zealand

“…The AGREE trial demonstrated that low-dose colchicine (1.2 mg, followed by 0.6 mg one hour later) for an acute gout flare was as effective as the higher dose regimen, with a lower incidence of gastrointestinal adverse effects. 7 Although this trial was small and conducted in patients with acute gout of less than 12 h duration, this study caused Australia to change its prescribing guidelines. 8 Already in place in Australia is the stipulation that the maximum quantity able to be dispensed is 30 tablets, with a maximum of five repeats i.e.…”