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Clinical and epidemiological research
Concise report
Allopurinol dose escalation to achieve serum urate below 6 mg/dL: an open-label extension study
  1. Lisa K Stamp1,2,
  2. Peter T Chapman2,
  3. Murray Barclay1,
  4. Anne Horne3,
  5. Christopher Frampton1,
  6. Paul Tan3,
  7. Jill Drake1,
  8. Nicola Dalbeth3
  1. 1Department of Medicine, University of Otago, Christchurch, New Zealand
  2. 2Department of Rheumatology, Immunology and Allergy, Christchurch Hospital, Christchurch, New Zealand
  3. 3Department of Medicine, University of Auckland, Auckland, New Zealand
  1. Correspondence to Professor Lisa K Stamp, Department of Medicine, University of Otago, Christchurch, P.O. Box 4345, Christchurch, New Zealand; lisa.stamp{at}cdhb.health.nz

Abstract

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

  • allopurinol
  • gout
  • serum urate

https://doi.org/10.1136/annrheumdis-2017-211873

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    Footnotes

    • 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.