The Gout TrEatment STrategy Project (GO TEST) Overture trial

Urate Lowering Therapy (ULT) plays an important role in the management of gout,
however it can be implemented through different strategies. In the absence of
high-quality evidence, international guidelines disagree which management
strategy is optimal. The GO TEST OVERTURE study aims to assess the relative
effect and cost effectiveness of two frequently used treatment strategies
regarding ULT. These two strategies are the Treat to Target strategy, aiming at
a serum uric acid of at least below 0.36 mmol/l and no complaints of
gout/patient acceptable symptom state, and the Treat tot Target strategy,
aiming only at the latter.

The GO TEST OVERTURE study aims to demonstrate the superiority of the Treat to
Target management strategy over a Treat to Avoid Symptoms approach in terms of
clinical remission of gout symptoms.

randomized, multicenter, pragmatic, superiority trial

Treat to Target

Patients in this group will be treated in accordance with the guidelines issued
by the Dutch association for rheumatology (NVR) and the *European League
against rheumatism* (EULAR). All patients initiate ULT at the start of the
study, with an initial low dose that is then titrated upward until the SUA
target of <36 µmol / l , or <30 µmol / l is reached. During the first 6 months
of the study, patients should be provided with prophylactic treatment against
flares and SUA levels should be monitored regularly, in accordance with local
procedures, until target SUA levels have been obtained. In the subsequent 18
months of the study, SUA levels will be measured at the 12 and 24 month study
visits, and medication should be adjusted if the treatment target is not/no
longer met. During the study period, rheumatoligsts may decide to schedule
additional routine care visits for monitoring of SUA levels if this is deemed
necessary.

Treat to avoid symptoms

Patients in this group will be treated in accordance with guidelines issued by
the American college for Physicians. The treating rheumatologist and patient
discuss the benefits and harms of initiating ULT including the option to not
start ULT, start only low (safe) dose ULT, or simultaneously initiate
anti-inflammatory prophylaxis, given the personal preferences and situation of
the patient. When patient and rheumatologist decide to refrain from initiating
ULT, recurrent flares can be treated if they occur with anti-inflammatory
medication (NSAIDS, colchicine, glucocorticoids) without starting ULT. SUA
levels will not be monitored, and no routine care visits are planned (12 and 24
months study visits are planned though), but patients will be instructed to
report gout flares in the study E-CRF. Patients who report > 1 gout flare in
the study CRF will be prompted to schedule a clinic visit. During these clinic
visits patients and clinicians will revisit their decision regarding ULT.

Patient risk

This study is primarily aimed at comparing different forms of follow-up to uric
acid lowering therapy. Various uric acid-lowering drugs and lifestyle advice
play an important role in this. During the study, rheumatologists are free to
prescribe uric acid-lowering drugs in consultation with the patients, with the
aim to get the serum urate level to or below the target value in the Treat to
Target group and with the aim to prevent recurrent symptoms in the Treat to
Avoid symptoms. However, all drugs prescribed used in this study should be
approved for use in gout in European countries and are
to be used in accordance with the EULAR recommendations for the treatment of
patients with gout, as well as the updated management guidelines for 2020
issued by American College for Rheumatology. Therefore, patients are not
exposed to additional treatment-related risks compared to routine clinical care
due to their participation in this study.

Patient burden

The study will not interfere with care provided for patients. Patients will
visit the rheumatology clinic once per year. Clinical measures performed for
this study are already part of routine care in The Netherlands. In addition to
the burden imposed on patients by routine clinical care, patients will have to
fill in questionnaires every three months, which might take approximately 20
minutes, each time