Intensive urate lowering for erosive gout is difficult to achieve and does not improve outcomes

Reference

Dalbeth N, Doyle AJ, Billington K, et al. Intensive serum urate lowering with oral urate-lowering therapy for erosive gout: a randomized double-blind controlled trial. Arthritis Rheumatol 2022;74(6):1059-1069.

Synopsis

In this study, which took place in New Zealand rheumatology clinics over a 2-year period, adults with gout and with at least one bone erosion in the feet were randomized to receive intensive urate lowering (target < 0.2 mmol/L [3.4 mg/dL]; n = 52) or standard therapy (target < 0.3 mmol/L [5 mg/dL]; n = 52). During the first 3 months of the study, participants had monthly visits with the researchers who used standardized protocols for escalating or altering therapy. Once the target urate level was maintained for 3 months, no additional changes were made unless the participants had medication-related adverse events. The protocol started with increasing allopurinol doses by 50 mg to 100 mg daily up to 900 mg, after which the researchers added 500 mg probenecid twice daily, which could be increased to 1 g twice daily. If the target wasn’t achieved, they replaced the medications with febuxostat followed by benzbromarone (a uricosuric that also inhibits xanthine oxidase; not available in the United States) plus allopurinol. Partway through the study, the researchers modified the use of febuxostat after the Food and Drug Administration raised concerns about cardiovascular harms. The authors used intention-to-treat analysis to compare erosion scores in each group. After 2 years of follow-up, 14% of the participants dropped out. After one year, only 53% of the intensive therapy group achieved the target compared with 83% of the standard therapy group. After 2 years, the rates were 62% and 83%, respectively. At the end of the study, erosions worsened by a similar degree in both groups and there was no difference in participants’ global assessments of disease activity, pain, quality of life, or anything else that might be meaningful. The intensive therapy group used higher doses of allopurinol (average 746 mg daily vs 497 mg daily). More important, 12 participants in the intensive therapy group required additional medication compared with only 2 participants in the standard therapy group (average number of medications 1.3 vs 1.0). Finally, serious adverse events occurred in 17% of the participants in each group.