Joint Ventures: Gout Management Gaps Persist Despite Effective Therapies, Guidelines

Treat-to-target versus flare-free: a critical distinction in gout care

Gout remains poorly managed at the population level despite a well-understood pathophysiology, established serum urate targets, and an expanding pharmacological toolkit, according to a recent episode of the rheumatology podcast Joint Ventures. Hosts Jack Arnold, MBBS, PhD, academic clinical lecturer in rheumatology at the University of Leeds, and Rihards Buss, MD, consultant rheumatologist at Freeman Hospital, Newcastle, reviewed current guidelines, emerging trial data, and the pipeline in gout management.

The central tension Arnold and Buss identify is the misattribution of flare-free intervals to adequate disease control in gout. Absence of flares does not confirm serum urate is at target, and it is target achievement, not symptom silence, predicting long-term outcomes. Both EULAR and ACR guidelines align on a serum urate target below 360 µmol/L (6 mg/dL) for most patients, and below 300 µmol/L (5 mg/dL) in tophaceous or severe disease.

Anti-inflammatory prophylaxis with colchicine, NSAIDs, or steroids should accompany urate-lowering therapy initiation and continue until patients are stable on a target-achieving dose, typically 3 to 6 months. In practice, colchicine is routinely prescribed for only 6 to 8 weeks, leaving patients underprotected during the period of highest vulnerability. Allopurinol dosing caps are frequently set too low: the maximum dose is 900 mg, and stopping at 300 mg without confirming target attainment is inadequate practice.

HLA-B*5801 screening prior to allopurinol initiation is conditionally recommended and limited to high-risk ancestry groups, specifically Southeast Asian and African American patients, not as a blanket policy. Arnold notes this is a point of unnecessary hesitation in practice, with some clinicians over-applying the screening recommendation beyond the populations for whom it is indicated.

Cardiovascular risk, treatment duration, and the gout drug pipeline

The cardiovascular dimension of gout extends well beyond joint disease. Buss argues the driver of cardiovascular risk is systemic inflammation from acute flares, not hyperuricemia per se, a distinction supported by the observation urate-lowering therapy in asymptomatic hyperuricemia without gout does not reduce cardiovascular events. Data presented by Cipolletta and colleagues at EULAR 2025, linking primary care records to hospitalization and mortality data across more than 116,000 gout patients in England and Sweden, showed significantly higher MACE-free survival and lower major adverse cardiovascular event risk in patients achieving a serum urate target of 360 µmol/L or below within one year of starting therapy.

Gout, Arnold notes, should be framed as a cardiovascular risk factor managed with the same rigor applied to hypertension or hyperlipidemia. Treating to a serum urate target within the first year carries prognostic significance beyond joint outcomes.

Treatment Duration and Drug Retention

On treatment duration, the GO TEST Finale trial, a Dutch open-label randomized superiority trial across nine rheumatology clinics enrolling 309 gout patients in remission, compared treat-to-target continuation of urate-lowering therapy against attempted discontinuation over 24 months. Continuation was clearly superior: cumulative flare incidence was 12.3% in the continuation group versus 31.8% in the discontinuation group, remission criteria were met in 79.2% versus 62.9%, and a modest kidney function benefit favored continuation. Both hosts are explicit: urate-lowering therapy is lifelong.

Drug retention in real-world practice falls off sharply within the first year. Buss advocates for structured gout annual reviews in primary care with compliance checked, serum uric acid measured, and dose adjusted, modeled on hypertension clinics. Patient education on the chronicity of treatment and the cardiovascular stakes of undertreated disease is central to improving outcomes at a population level.

The pipeline is active across drug classes. URAT1 inhibitors including dotinurad, already widely used in Japan and China, are advancing through Western trials with improved renal safety profiles suited to the CKD-heavy gout population. Pegloticase, a uricase-based agent unavailable in Europe, carries risks of infusion reactions and rapid drug neutralization via anti-drug antibody formation; newer formulations aim to incorporate immunosuppression into the molecule itself, with a phase 3 program currently underway.

Canakinumab, an IL-1 inhibitor licensed for gout flares in patients intolerant of NSAIDs or colchicine, has an extended half-life with potential for incidental prophylactic effect, though it is not licensed for prevention and its cost limits broad use. Anakinra, widely used off-label for IL-1 blockade in gout, comes off patent imminently, a development Arnold and Buss expect to broaden access to IL-1 inhibition broadly. SGLT2 inhibitors reduce gout incidence and need for gout-specific therapy in patients treated for type 2 diabetes via increased renal urate excretion, an effect not seen with GLP-1 receptor agonists, and may emerge as a useful adjunct to allopurinol pending larger trial data.

“[Don’t] confuse flare free with at target. They’re 2 different things. You can be massively lulled into a false sense of security with patients being flare-free, and in fact, they’ll be very happy with you. But it is more important — there is more at play than that,” Arnold said.

Arnold’s disclosures include Alumis, Roche, and Novartis. Buss has no relevant disclosures to report.

References

1. Cipolletta E, et al. Cardiovascular outcomes of treat-to-target versus fire-and-forget urate-lowering treatment in gout: emulated target trial studies using linked English and Swedish primary care, hospitalisation and mortality data. Presented at: EULAR Annual Congress 2025; June 2025; Barcelona, Spain. doi:10.1136/annrheumdis-2025-eular.B1714

2. GO TEST Finale: treat-to-target continuation of urate-lowering therapy versus a urate-lowering therapy discontinuation attempt strategy in gout patients in remission. Presented at: EULAR Annual Congress 2026; June 3-6, 2026; London, United Kingdom. doi:10.1136/annrheumdis-2026-eular.B.833