1. Robert A. Terkeltaub, Daniel E. Furst, Katherine Bennett, Karin A. Kook, R. S. Crockett, and Matthew W. Davis ARTHRITIS & RHEUMATISM Vol. 62, No. 4, April 2010, pp 1060–1068 High Versus Low Dosing of Oral Colchicine for Early Acute Gout Flare R2 Kim Hyuck / Prof. Son Kyeong Min

2. Introduction Colchicine : mainly used in the treatment and prophylaxis of gout flare –the evidence basis : remarkably limited (Only 1 randomized, placebo-controlled trial,n =43) The AGREE (Acute Gout Flare Receiving Colchicine Evaluation) – study compared low- and high-dose colchicine –randomized, placebo-controlled design. –Pharmacokinetic profiles : comparable maximum blood concentrations (Cmax). –high-dose regimen : 4.8 mg total over 6 hours –low-dose regimen :1.8 mg total over 1 hour

3. Patient and methods Characterization of colchicine pharmacokinetics In healthy volunteers who had fasted –low-dose colchicine :1.2 mg followed by 0.6 mg in 1 hour [1.8 mg total] –high-dose colchicine :1.2 mg followed by 0.6 mg every hour for 6 hours [4.8 mg total] –single-dose colchicine : 0.6 mg

4. Patient and methods6.84 2.5 6.19

5. AGREE study population Male and postmenopausal female patients –>18 years of age with a confirmed past diagnosis of gout total of 575 patients total of 575 patients –randomized to 1 of 3 treatment groups – 1) “low-dose” colchicine, 2) “high-dose” colchicine, 3)placebo

6. Patient and methods AGREE study design Multicenter(54), randomized, double-blind, placebo- controlled, parallel-group, dose comparison between April 2007 and October 2008 The patient : a standardized diary – pain, symptoms, adverse events (AEs), and rescue medication use(e.g. NSAID)

7. Patient and methods AGREE statistical analysis and end points The primary end point : >50% pain reduction at 24 hours without rescue medication (e.g. NSAID) The primary analysis –Comparison of high-dose colchicine and placebo groups –Comparison of low dose colchicine with placebo groups

8. Result Characteristics of the AGREE study subjectsFindings of the AGREE efficacy evaluationFindings of the AGREE safety evaluation

9. Result : Characteristics of the AGREE study subjects. AGREE (Acute Gout Flare Receiving Colchicine Evaluation) patient flow diagram

10. Result : Characteristics of the AGREE study subjects. Baseline characteristics of the patients

11. Result : Findings of the AGREE efficacy evaluation Efficacy analysis

12. Result : Findings of the AGREE efficacy evaluation Distribution of percent improvement

13. Result : Findings of the AGREE safety evaluation Incidence of most frequent adverse events

14. ConclusionEfficacySafty low-dose colchicine High-dose colchicine low-dose colchicine High-dose colchicine