Colchicine Concentrations and Relationship With Colchicine Efficacy and Adverse Events: Post Hoc Analysis of a Randomized Clinical Trial of Colchicine for Gout Flare Prophylaxis

OBJECTIVE: Our objective was to examine the relationship between colchicine plasma concentrations and clinical and demographic factors and to determine the relationship between colchicine concentrations and colchicine efficacy and colchicine-specific adverse events. METHODS: Post hoc analyses were undertaken using data from a 12-month randomized controlled trial involving 200 people with gout that compared low-dose colchicine to placebo for the first six months while starting allopurinol, with a further six-month follow-up. Steady-state colchicine plasma concentrations were measured 30 to 80 minutes post dose (assumed peak) and just before the dose (trough) at month three, and creatine kinase (CK) levels were measured at months zero, three, and six. Self-reported gout flares, adverse events, and serious adverse events were collected monthly. RESULTS: Peak and trough colchicine concentrations were available for 79 participants in the colchicine arm. Multivariable analysis showed that those taking a statin and non-Māori and non-Pacific ethnicity were independently associated with higher trough concentrations, and age older than 60 years was independently associated with higher peak concentrations. Trough and peak colchicine concentrations were significantly higher in those who had any adverse event between months four and six. However, there was no association between colchicine concentrations and colchicine-specific adverse events (gastrointestinal and muscle) or with CK changes in the colchicine-treated patients. CONCLUSION: Trough or peak colchicine concentrations are not associated with gout flare prophylaxis efficacy. There is no consistent relationship between colchicine concentrations and colchicine-specific adverse events. Although colchicine concentrations increase with concomitant statin use, this does not result in muscle-related adverse events. These findings indicate that colchicine therapeutic drug monitoring is of limited value in clinical practice.