Anusha Moses (1), Martijn Oude Voshaar (2,3), Tim Jansen (4), Mart Van de Laar (5)
Affiliation(s):
1. University of Twente, Department of Personalized Diagnostics and Therapeutics Department of Personalized Diagnostics and Therapeutics/ Medical Cell BioPhysics &TechMed Center, Enschede, Netherlands,
2. Erasmus Medical Center, Department of Public Health, Rotterdam, Netherlands,
3. University of Twente, Department of Personalized Diagnostics and Therapeutics/ Medical Cell BioPhysics & TechMed Center, Enschede, Netherlands,
4. Viecuri Medical Center, Department of Rheumatology, Venlo, Netherlands, 5University of Twente, Department of Psychology, Enschede, Netherlands
Background: Both the European League Against Rheumatism (EULAR) and the American College for Rheumatology (ACR) state that gout can be effectively managed by reducing sUA levels below the physiological threshold of saturation using Urate Lowering Therapy (ULT), a Treat to Target approach (T2T). An alternative, more reactive management strategy, advocated by the American College of Physicians (ACP) is to treat symptoms and to base the start and dosing of ULT on avoiding (recurrent) symptoms, without monitoring sUA levels. This treat-to-avoid symptom (T2S) approach has been criticized by rheumatologists for potentially ignoring ongoing urate deposition until potentially severe disease manifestations become apparent. Although the solid underlying mechanism of gout is ignored, the lack of a head-to-head comparison of both strategies led the ACP to advise the T2S strategy for the treatment of gout.
Objectives: The objective of the Gout TrEatment Strategy (GO TEST) OVERTURE trial is to compare a T2T strategy versus a T2S strategy for the management of gout.
Methods: GO TEST OVERTURE study is a multicenter randomised controlled open-label pragmatic trial. Patients with a clinical diagnosis of gout, fulfilling the 2015 ACR-EULAR criteria, currently not using ULT but with an indication for the use of ULT were included. Patients with a contraindication for allopurinol, benzbromarone, and febuxostat including those with an eGFR< 30ml/minute were excluded from the study. Patients in the T2T group started ULT at the discretion of the attending physician. Their sUA levels were regularly measured and ULT dosages were titrated to achieve a sUA target of <0.36mmol/L. In the T2S group, patients were instructed to self-monitor their gout symptoms and to contact the clinic in case of recurrent symptoms, with a potential ULT dosage increase in case of flare recurrence. The incidence of patient-reported gout flares was assessed every three months using the Gaffo gout flare criteria. Major outcomes of the study were the proportions of patients meeting the sUA target and the number of Gaffo flares during 1- year follow-up. The proportions of patients achieving the sUA target level were compared using z-tests for proportions. The number of flares over 1 year was compared using Poisson regression analysis.
Results: A total of 308 patients were eligible and included in the trial (T2T n=145; T2S n=163) with a mean sUA of 0.5 and 0.4 mMol/L and mean age of 62.5 at baseline in each group respectively. After 1-year, the proportion of patients achieving the target sUA level <0.36 mmol/l s was significantly higher in the T2T group (77%) than in the T2S group (29%) (p<0.001). In addition, the incidence rate ratio for gout flares was 1.541 for T2S versus
T2T (p <0.001), indicating that patients in the T2S group experienced a 54% increase in the rate of gout flares.
Conclusion: Our study is the first randomized trial to directly compare T2T with T2S as a control group in gout. We were able to show the superiority of the T2T management approach in gout.