Abstract
Objectives: Our objective was to examine the relationship between colchicine plasma concentrations and clinical/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 RCT involving 200 people with gout which compared low-dose colchicine to placebo for the first six months while starting allopurinol, with a further 6-month follow-up. Steady-state colchicine plasma concentrations were measured 30-80 minutes post-dose (assumed peak) and just prior to the dose (trough) at month 3 and creatine kinase (CK) at months 0, 3 and 6. 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 on a statin and non-Māori/non-Pacific ethnicity were independently associated with higher trough concentrations, and age over 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 month 4 and 6. 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. Interpretation Trough or peak colchicine concentrations do not associate 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 adverse events. These findings indicate that colchicine therapeutic drug monitoring is of limited value in clinical practice.