PMID- 28314755 OWN - NLM STAT- MEDLINE DCOM- 20170821 LR - 20170821 IS - 1468-2060 (Electronic) IS - 0003-4967 (Linking) VI - 76 IP - 9 DP - 2017 Sep TI - A randomised controlled trial of the efficacy and safety of allopurinol dose escalation to achieve target serum urate in people with gout. PG - 1522-1528 LID - 10.1136/annrheumdis-2016-210872 [doi] AB - OBJECTIVES: To determine the efficacy and safety of allopurinol dose escalation using a treat-to-target serum urate (SU) approach. METHODS: A randomised, controlled, parallel-group, comparative clinical trial was undertaken. People with gout receiving at least creatinine clearance (CrCL)-based allopurinol dose for >/=1 month and SU >/=6 mg/dL were recruited. Participants were randomised to continue current dose (control) or allopurinol dose escalation for 12 months. In the dose escalation group, allopurinol was increased monthly until SU was <6 mg/dL. The primary endpoints were reduction in SU and adverse events (AEs). RESULTS: 183 participants (93 control, 90 dose escalation) were recruited. At baseline, mean (SD) urate was 7.15 (1.6) mg/dL and allopurinol dose 269 mg/day. 52% had CrCL<60 mL/min. Mean changes in SU at the final visit were -0.34 mg/dL in the control group and -1.5 mg/dL in the dose escalation group (p<0.001) with a mean difference of 1.2 mg/dL (95% CI 0.67 to 1.5, p<0.001). At month 12, 32% of controls and 69% in the dose escalation had SU <6 mg/dL. There were 43 serious AEs in 25 controls and 35 events in 22 dose escalation participants. Only one was considered probably related to allopurinol. Five control and five dose escalation participants died; none was considered allopurinol related. Mild elevations in LFTs were common in both groups, a few moderate increases in gamma glutamyl transferase (GGT) were noted. There was no difference in renal function changes between randomised groups. CONCLUSIONS: Higher than CrCL-based doses of allopurinol can effectively lower SU to treatment target in most people with gout. Allopurinol dose escalation is well tolerated. TRIAL REGISTRATION NUMBER: ANZCTR12611000845932; Results. CI - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/. FAU - Stamp, Lisa K AU - Stamp LK AD - Department of Medicine, University of Otago, Christchurch, Christchurch, New Zealand. AD - Department of Rheumatology, Immunology and Allergy, Christchurch Hospital, Christchurch, New Zealand. FAU - Chapman, Peter T AU - Chapman PT AD - Department of Rheumatology, Immunology and Allergy, Christchurch Hospital, Christchurch, New Zealand. FAU - Barclay, Murray L AU - Barclay ML AD - Department of Medicine, University of Otago, Christchurch, Christchurch, New Zealand. FAU - Horne, Anne AU - Horne A AD - Department of Medicine, University of Auckland, Auckland, New Zealand. FAU - Frampton, Christopher AU - Frampton C AD - Department of Medicine, University of Otago, Christchurch, Christchurch, New Zealand. FAU - Tan, Paul AU - Tan P AD - Department of Medicine, University of Auckland, Auckland, New Zealand. FAU - Drake, Jill AU - Drake J AD - Department of Medicine, University of Otago, Christchurch, Christchurch, New Zealand. FAU - Dalbeth, Nicola AU - Dalbeth N AD - Department of Medicine, University of Auckland, Auckland, New Zealand. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20170317 PL - England TA - Ann Rheum Dis JT - Annals of the rheumatic diseases JID - 0372355 RN - 0 (Gout Suppressants) RN - 268B43MJ25 (Uric Acid) RN - 63CZ7GJN5I (Allopurinol) RN - EC 2.3.2.2 (gamma-Glutamyltransferase) RN - EC 2.6.1.1 (Aspartate Aminotransferases) RN - EC 2.6.1.2 (Alanine Transaminase) RN - EC 3.1.3.1 (Alkaline Phosphatase) SB - IM MH - Aged MH - Alanine Transaminase/blood MH - Alkaline Phosphatase/blood MH - Allopurinol/*administration & dosage MH - Aspartate Aminotransferases/blood MH - Chemical and Drug Induced Liver Injury/blood/etiology MH - Dose-Response Relationship, Drug MH - Female MH - Gout/blood/*drug therapy MH - Gout Suppressants/*administration & dosage MH - Humans MH - Male MH - Middle Aged MH - *Patient Care Planning MH - Treatment Outcome MH - Uric Acid/*blood MH - gamma-Glutamyltransferase/blood OTO - NOTNLM OT - Gout OT - Outcomes research OT - Treatment COIS- 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 from Health Research Council of New Zealand, grants and personal fees from AstraZeneca, grants and personal fees from Ardea Biosciences, personal fees from Takeda, personal fees from Teijin, personal fees from Menarini, grants from Fonterra, personal fees from Pfizer, personal fees from Crealta, personal fees from Cymabay, outside the submitted work. EDAT- 2017/03/21 06:00 MHDA- 2017/08/22 06:00 CRDT- 2017/03/19 06:00 PHST- 2016/11/24 00:00 [received] PHST- 2017/02/21 00:00 [revised] PHST- 2017/02/22 00:00 [accepted] PHST- 2017/03/21 06:00 [pubmed] PHST- 2017/08/22 06:00 [medline] PHST- 2017/03/19 06:00 [entrez] AID - annrheumdis-2016-210872 [pii] AID - 10.1136/annrheumdis-2016-210872 [doi] PST - ppublish SO - Ann Rheum Dis. 2017 Sep;76(9):1522-1528. doi: 10.1136/annrheumdis-2016-210872. Epub 2017 Mar 17.