Treat-to-target strategy improves gout remission vs symptom-driven care

BACKGROUND: A treat-to-target approach is recommended for gout management, which involves titrating urate-lowering therapy to reach a serum urate target of less than 0·36 mmol/L, but evidence from pragmatic, head-to-head trials comparing a treat-to-target strategy with a symptom-driven approach is scarce. We aimed to address this gap by comparing these two approaches in patients with gout. METHODS: We did a multicentre, open-label, pragmatic, superiority, randomised controlled trial at eight secondary care rheumatology centres in the Netherlands. Participants aged 18 years or older with gout and hyperuricaemia (typically defined as a serum urate concentration of >0·36 mmol/L), and not currently using urate-lowering therapy were randomly assigned (1:1) using a computer-generated allocation sequence to receive either a treat-to-target strategy to reach a target serum urate concentration of less than 0·36 mmol/L with structured serum urate-guided titration of oral urate-lowering therapy (including first-line allopurinol and second-line oral febuxostat or oral benzbromarone) or symptom-driven management, in which the physicians and patients decided whether to initiate urate-lowering therapy based on symptoms, and the type and dose were determined at the physician's discretion without a specific serum urate target. Because of the pragmatic design, participants and investigators were not masked to treatment allocation. The primary outcome was remission during months 18-24 of follow-up, defined as absence of gout flares during months 18-24, no subcutaneous tophi at month 24, a patient-reported pain score of less than 2, and a patient global assessment of disease activity score of more than 8. Analyses were done according to the intention-to-treat principle using multiple imputation for missing data, and all randomly assigned participants were included in the primary efficacy and safety analyses. People with lived experience of gout contributed to the study design and selection of outcome measures. The trial was registered with EudraCT, 2020-005721-82, and is closed to recruitment. FINDINGS: Between March 4, 2021, and Nov 4, 2022, 308 participants were randomly assigned, of whom 268 (87%) were male and 40 (13%) were female; the mean age was 65·93 years (SD 15·29). Participants were allocated to the treat-to-target group (145 participants) or the symptom-driven management group (163 participants). Remission during months 18-24 occurred more often in the treat-to-target group than in the symptom-driven management group (39·4% [57 of 145 participants] vs 24·0% [39 of 163]; absolute difference 15·4 percentage points [95% CI 6·4-24·4]; p=0·024). Adverse events occurred in 61 (42%) participants in the treat-to-target group and 86 (53%) in the symptom-driven management group (absolute difference -10·7 percentage points [95% CI -21·8 to 0·4; p=0·060). No serious drug-related adverse events and no treatment-related deaths were reported. INTERPRETATION: A treat-to-target strategy was associated with improved long-term disease control compared with symptom-driven care, without evidence of increased adverse events. These findings provide support for the use of systematic serum urate-guided urate-lowering therapy titration in the routine management of gout. FUNDING: ZonMW and Reuma Nederland.