PhD Defence Anusha Moses | Treat-to-Target in Gout: Clinical Outcomes, Patient-Reported Outcomes and Cost-Effectiveness

Treat-to-Target in Gout: Clinical Outcomes, Patient-Reported Outcomes and Cost-Effectiveness

Anusha Moses is a PhD student in the department Medical Cell Biophysics. (Co)Promotors are prof. dr. M.A.F.J. van de Laar & dr. A.H. Oude Voshaar from the faculty Science & Technlogy (TNW), University of Twente and dr. T.J. Jansen from Viecuri Medical Center.

Gout, the most prevalent inflammatory arthritis, results from sustained hyperuricaemia and monosodium urate crystal deposition. Clinical guidelines remain divided: the ACR and EULAR endorse treat-to-target (T2T), systematic titration of urate-lowering therapy (ULT) to a serum urate target of <0.36 mmol/L, whereas the ACP advocates treat-to-avoid-symptoms (T2S), a symptom-driven approach without biochemical targets. No randomised controlled trial had directly compared these strategies. The GO-TEST Overture trial was a pragmatic, multicentre, open-label, superiority RCT conducted across 8 Dutch rheumatology centres. Between March 2021 and November 2022, 308 patients with gout and hyperuricaemia were randomised 1:1 to T2T (n=145) or T2S (n=163), with 24 months of follow-up. The primary outcome was remission during months 18–24. A trial-based cost-utility analysis was conducted from a Dutch societal perspective, and a longitudinal Rasch validation of the Dutch HAQ-II was performed within the COSMIN framework at baseline, 12, and 24 months. Remission was significantly higher with T2T than T2S (39.4% vs 24.0%; +15.4 percentage points, 95% CI 6.4–24.4; p=0.024; NNT≈7), alongside greater serum urate target attainment (72.8% vs 39.5%), lower annualised flare rates (IRR 0.62, 95% CI 0.44–0.88), and fewer non-serious adverse events (17% vs 29%). T2T was associated with lower mean societal costs (€5,486 vs €5,633) and higher QALYs (1.412 vs 1.362), yielding a 76% probability of cost-effectiveness at €50,000/QALY. The Dutch HAQ-II demonstrated excellent reliability (EAP 0.92–0.93) and structural validity (RMSEA 0.067–0.071, CFI 0.94–0.95) across timepoints; the extended 12-item version showed superior reliability, responsiveness, and floor-effect reduction relative to the standard 10-item version, with partial longitudinal non-invariance identified in four items reflecting genuine gains in functional capacity. This thesis provides the first randomised evidence that T2T achieves superior clinical outcomes and is cost-effective relative to T2S in gout, while validating the Dutch HAQ-II as a robust patient-reported outcome measure for gout trials. These findings directly address the evidentiary gap underlying current guideline disagreement and support implementation of structured T2T strategies in clinical practice.