Objectives To determine the long-term safety and efficacy of allopurinol dose escalation (DE) to achieve target serum urate (SU) in gout.
Methods People, including those with chronic kidney disease, who completed the first 12 months of a randomised controlled trial continued into a 12-month extension study. Participants randomised to continue current dose for the first 12 months began allopurinol DE at month 12 if SU was ≥6 mg/dL (control/DE). Immediate DE participants who achieved target SU maintained allopurinol dose (DE/DE). The primary endpoints were reduction in SU and adverse events (AEs) at month 24.
Results The mean (SE) change in SU from month 12 to 24 was −1.1 (0.2) mg/dL in control/DE and 0.1 (0.2) mg/dL in DE/DE group (p<0.001). There was a significant reduction in the percentage of individuals having a gout flare in the month prior to months 12 and 24 compared with baseline in both groups and in mean tophus size over 24 months, but no difference between randomised groups. There were similar numbers of AEs and serious adverse events between groups.
Conclusions The majority of people with gout tolerate higher than creatinine clearance-based allopurinol dose and achieve and maintain target SU. Slow allopurinol DE may be appropriate in clinical practice even in those with kidney impairment.
Trial registration number ACTRN12611000845932
- serum urate
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Handling editor Tore K Kvien
Contributors LKS and ND: literature search, study design, data collection, data analysis, data interpretation, manuscript preparation. PTC and JD: study design, data collection, data analysis, data interpretation, manuscript preparation. MB and CF: study design, data analysis, data interpretation, manuscript preparation. AH and PT: data collection, data analysis, data interpretation, manuscript preparation.
Funding This study was funded by the Health Research Council of New Zealand.
Competing interests LKS reports grants from Health Research Council of New Zealand during the conduct of the study; grants from Ardea Biosciences; grants from Health Research Council of New Zealand, outside the submitted work. AH reports grants from Health Research Council of New Zealand during the conduct of the study. ND reports grants from Health Research Council of New Zealand during the conduct of the study; grants and personal fees from AstraZeneca and Ardea Biosciences; personal fees fromTakeda, Teijin and Menarini; grants from Fonterra; personal fees from Pfizer, Crealta and Cymabay, outside the submitted work. PTC, MB, CF, JD and PT have nothing to disclose.
Patient consent Obtained.
Ethics approval Multiregional ethics committee of New Zealand.
Provenance and peer review Not commissioned; externally peer reviewed.
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