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.
- Outcomes research
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Handling editor Tore K Kvien
Contributors LKS and ND: literature search, study design, data collection, data analysis, data interpretation and manuscript preparation. PTC and JD: study design, data collection, data analysis, data interpretation and manuscript preparation. MLB and CF: study design, data analysis, data interpretation and manuscript preparation. AH and PT: data collection, data analysis, data interpretation and manuscript preparation.
Funding This study was funded by the Health Research Council of New Zealand (11/203).
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.
Patient consent Obtained.
Ethics approval MultiRegional Ethics Committee of New Zealand.
Provenance and peer review Not commissioned; externally peer reviewed.