Allopurinol dose escalation to achieve serum urate below 6 mg/dL: an open-label extension study

ObjectivesTo determine the long-term safety and efficacy of allopurinol dose escalation (DE) to achieve target serum urate (SU) in gout.MethodsPeople, including those with chronic kidney disease, who completed the first 12 months of a randomised controlled trial continued into a 12-month extension s...

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Published inAnnals of the rheumatic diseases Vol. 76; no. 12; pp. 2065 - 2070
Main Authors Stamp, Lisa K, Chapman, Peter T, Barclay, Murray, Horne, Anne, Frampton, Christopher, Tan, Paul, Drake, Jill, Dalbeth, Nicola
Format Journal Article
LanguageEnglish
Published England BMJ Publishing Group LTD 01.12.2017
Subjects
Aged
Allopurinol
Allopurinol - administration & dosage
Arthritis
Creatinine
Dose-Response Relationship, Drug
Drug dosages
Female
Gout
Gout - blood
Gout - drug therapy
Gout Suppressants - administration & dosage
Humans
Kidney transplantation
Male
Middle Aged
Rheumatism
Rheumatology
Systematic review
Time Factors
Treatment Outcome
Uric acid
Uric Acid - blood
allopurinol
serum urate
gout
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Summary:ObjectivesTo determine the long-term safety and efficacy of allopurinol dose escalation (DE) to achieve target serum urate (SU) in gout.MethodsPeople, 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.ResultsThe 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.ConclusionsThe 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 numberACTRN12611000845932
ISSN:0003-4967
1468-2060
DOI:10.1136/annrheumdis-2017-211873