Findings support treat-to-target over symptom-driven management for gout

medwireNews: A treat-to-target approach may be better than symptom-driven care for improving long-term gout control without increasing the risk for adverse events (AEs), suggest findings from the GO TEST Overture trial.

The “[European Alliance of Associations for Rheumatology] and [American College of Rheumatology] support lowering serum urate to a target (treat to target), whereas the [American College of Physicians] recommends symptom-driven management, citing insufficient evidence that targeting serum urate improves patient-centred outcomes,” observe the researchers.

“This trial directly addresses that gap, showing that a treat-to-target strategy results in superior disease control without additional safety concerns.”

The open-label trial was conducted in eight clinical practices in the Netherlands and involved 308 adults (mean age 66 years; 87% men) with gout and hyperuricemia (serum urate concentration >0.36 mmol/L) who were not receiving urate-lowering therapy. Subcutaneous tophi were present in 14% of patients.

The study participants were randomly assigned to follow either a treat-to-target strategy to achieve a target urate concentration of less than 0.36 mmol/L (<0.30 mmol/L in patients with subcutaneous tophi) or to receive symptom-driven management.

The 145 patients in the treat-to-target group started on oral allopurinol 100 mg/day (titrated up to a maximum of 900 mg/day). If allopurinol was contraindicated or not tolerated, patients were given either febuxostat 80 mg every other day (up to 120 mg/day), or benzbromarone 50 mg/day (up to 100 mg/day).

For the 163 patients receiving symptom-drive management, initiation of urate-lowering therapy was jointly decided by the patient and their rheumatologist based on “individual preferences and perceived risk,” say Anusha Moses (University of Twente, Enschede, the Netherlands) and colleagues. The type and dose of treatment was at the physician’s discretion.

Serum urate levels were monitored regularly in patients in the treat-to-target group for the first 6 months, with prophylactic anti-inflammatory treatment, consisting of low-dose colchicine, nonsteroidal anti-inflammatory drugs, or oral corticosteroids, such as prednisolone, provided as needed to prevent gout flares. Patients in the symptom-driven management group did not receive routine serum monitoring and recurrent flares were treated symptomatically with anti-inflammatories.

During months 18–24, 39.4% of patients in the treat-to-target group and 24.0% in the symptom-driven group achieved remission. This was defined as the simultaneous presence of four criteria: absence of subcutaneous tophi at 24 months; sustained low patient-reported pain (<2 points on an 11-point numerical rating scale [NRS]) at 18, 21, and 24 months;  a low patient global assessment score (NRS >8 points) at 18, 21, and 24 months; and the absence of gout flares during months 18–24.

The absolute difference in remission rates was a significant 15.4 percentage points in favor of the treat-to-target strategy.

“[T]he benefit of the treat-to-target strategy was primarily driven by substantially higher rates of serum urate target attainment and fewer gout flares than with symptom-driven management,” observe the study authors.

Serum urate targets were achieved by 72.8% of patients in the treat-to-target group at months 18–24 compared with 39.5% of patients in the symptom-driven management group, at a significant difference of 33.3 percentage points. Gout flares were absent in a corresponding 64.2% and 48.3%, giving a significant difference of 15.9 percentage points.

“Overall, both strategies showed an acceptable safety profile,” Moses et al write in The Lancet Rheumatology.

AEs occurred in 42% of participants in the treat-to-target arm and 53% of those in the symptom-driven management arm, a nonsignificant difference. The serious AE rates were a comparable 26% and 23%, respectively, and none were considered related to study treatment. Nine patients in the treat-to-target group died, as did seven of those in the symptom-driven management arm; all deaths were unrelated to study treatment.

“These findings offer empirical support for guideline recommendations that advocate a urate-lowering treatment strategy aimed at attaining and maintaining serum urate concentrations below 0.36 mmol/L,” the study authors conclude.

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Lancet Rheumatol 2026; doi:10.1016/ S2665-9913(26)00034-2