Abstract
Background: Low dose oral colchicine (0.5mg once or twice daily) is one of the first line recommended therapies for prevention of gout flares when commencing urate-lowering therapy. While colchicine may be effective, it has a number of potential adverse events, of which the most common are gastrointestinal, including nausea and diarrhoea. In general, gastrointestinal adverse events are dose-dependent. To date no studies have specifically examined the relationship of colchicine concentrations with clinical efficacy and/or colchicine-specific adverse events in people with gout.
Objectives: To examine the relationship between colchicine plasma concentrations and clinical/demographic factors, and to determine the relationship between colchicine concentrations and colchicine efficacy (defined as occurrence of gout flares) 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. Creatine kinase (CK) was measured at months 0, 3 and 6. Self-reported gout flares, adverse events and serious adverse events were collected monthly. Peak and trough colchicine concentrations at month 3 were compared between the demographic and clinical features using 1-way ANOVA. Similarly, these concentrations were compared between the occurrence of gout flares and the presence of treatment emergent adverse events using 1-way ANOVA.
Results: Peak and trough colchicine concentrations were available for 79 participants in the colchicine arm. As expected, mean trough colchicine concentrations were lower than mean peak concentrations (0.30ng/ml vs 0.61ng/ml p<0.001). 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. There was no association between colchicine concentrations at month 3 and experience of at least one gout flare between months 0-3 or months 4-6. There was no association between colchicine concentration at month 3 and experience of at least one gout flare between months 7-9, the period immediately after the colchicine had been stopped. Trough and peak colchicine concentrations were significantly higher in those who had any AE between month 4 and 6. However, there was no significant association between colchicine concentrations and colchicine-specific adverse events (gastrointestinal and muscle), or with CK changes in the colchicine treated patients. There was no significant correlation between trough or peak colchicine concentrations and CK at month three (r=-0.17; p=0.13 and r=-0.12; p=0.30 respectively).
Conclusions: 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 routine clinical practice.
Poster presentation.