Abstract

Background:Initiation of urate lowering therapy (ULT) is associated with an increase in gout flares1. Therefore, guidelines advice prophylactic therapy during the first six months of ULT2. Colchicine 0.5-1 mg/day is recommended. Whether 1 mg/day colchicine is superior to 0.5 mg/day is unknown.Objectives:To examine the difference in gout flares in the first six months after initiation of ULT between 0.5 and 1.0 mg/day colchicine prophylaxis.Methods:Patients with clinical diagnosis of gout, a first outpatient visit between January 2010 and March 2018 and a follow-up of at least 6 months were included in a retrospective cohort study, conducted in two rheumatology centres in the Netherlands. Within this cohort, patients starting ULT and colchicine prophylaxis were selected. Difference in gout flare incidence density (ID) in the first six months after start of ULT between colchicine 0.5 and 1.0 mg/day was analysed using Poisson regression, corrected for confounders. Secondary analyses included the proportion of patients reaching a target of serum urate acid (SUA) of < 0.36 mmol/l within the first six months.Results:Of 2108 gout patients, 379 patients started ULT and used colchicine prophylaxis (table 1). ID of flares was 2.8 and 2.6 per patient year on colchicine 1.0 and 0.5 mg/day respectively, resulting in an incidence rate ratio of 1.05 (95% CI 0.86 – 1.27). Within the first six months 68% in the colchicine 1mg/day and 63% in the colchicine 0.5 mg/day reached their target (difference 5%, 95% CI -0.08 – 0.18).Table 1.Baseline patient, disease and treatment characteristicsColchicine prophylaxis0,5 mg/day (n=275)1 mg/day (n=104)Men, no. (%)226 (82%)88 (85%)Age, years67.3 (58.8-76.3)65.3* (54.4-71.9)BMI, kg/m229.0 (26.1-32.1)29.5 (27.9-31.6)Comorbidity no. (%) Hypertension146 (53%)54 (52%) Diabetes Mellitus66 (24%)24 (23%) Hypercholesterolemia43 (16%)15 (14%) Renal insufficiency56 (20%)18 (17%) Crystal-confirmed diagnosis, no. (%)197 (72%)77 (74%) Serum urate acid at start ULT (mmol/l), mean ± SD0.51 ± 0.110.50 ± 0.11ULT medication, no. (%) Allopurinol272 (99%)103 (99%) Benzbromaron2 (0.6%) Febuxostat1 (0.4%)1 (1%)*Compared to colchicine 0,5 mg/day, P<0.05.**No SD possible, n = 1.Conclusion:Use of 1 mg/day colchicine is not superior to 0.5 mg/day as prophylaxis for ULT induced gout flares. For generalisability it should be noted that flare rates were not very high, probably due to the background ULT being characterised by a “start low, go slow” approach. In this context colchicine 0.5 mg/day is sufficient as prophylaxis.

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