A treat-to-target strategy versus symptom-driven management of gout in the Netherlands (GO TEST Overture): a multicentre, open-label, pragmatic, superiority, randomised controlled trial.

We aimed to address this gap by comparing these two approaches in patients with gout.

我们旨在通过比较这两种方法在痛风患者中的效果来填补这一空白。

Methods

We did a multicentre, open-label, pragmatic, superiority, randomised controlled trialat eight secondary care rheumatology centres in the Netherlands.

我们在荷兰的八个二级护理风湿病中心进行了一项多中心、开放标签、实用、优越性、随机对照试验。

Participants aged 18 years or older with gout and hyperuricaemia (typically defined as a serum urate concentration of >0·36 mmol/L), and not currently using urate-lowering therapy were randomly assigned (1:1) using a computer-generated allocation sequence to receive either a treat-to-target strategy to reach a target serum urate concentration of less than 0·36 mmol/L with structured serum urate-guided titration of oral urate-lowering therapy (including first-line allopurinol and second-line oral febuxostat or oral benzbromarone) or symptom-driven management, in which the physicians and patients decided whether to initiate urate-lowering therapy based on symptoms, and the type and dose were determined at the physician's discretion without a specific serum urate target.

年龄在18岁或以上的痛风和高尿酸血症患者（通常定义为血清尿酸浓度>0·36毫摩尔/升），且目前未使用降尿酸治疗的患者，通过计算机生成的分配序列以1:1的比例随机分配，接受目标导向策略以达到目标血清尿酸浓度小于0·36毫摩尔/升，并通过口服降尿酸治疗（包括首选别嘌呤醇和次选口服非布司他或口服苯溴马隆）的结构化血清尿酸指导下的滴定，或者症状驱动管理，在这种管理中，医生和患者根据症状决定是否启动降尿酸治疗，类型和剂量由医生自行决定，没有特定的血清尿酸目标。

Because of the pragmatic design, participants and investigators were not masked to treatment allocation.

由于实用的设计，参与者和研究人员无法对治疗分配进行盲法处理。

The primary outcome was remission during months 18-24 of follow-up, defined as absence of gout flares during months 18-24, no subcutaneous tophi at month 24, a patient-reported pain score of less than 2, and a patient global assessment of disease activity score of more than 8.

主要结果是在随访的第18至24个月期间的缓解，定义为在第18至24个月期间没有痛风发作，第24个月没有皮下痛风石，患者报告的疼痛评分低于2，以及患者对疾病活动度的总体评估得分超过8。

Analyses were done according to the intention-to-treatprinciple using multiple imputation for missing data, and all randomly assigned participants were included in the primary efficacy and safety analyses.

分析是根据意向治疗原则进行的，使用多重插补处理缺失数据，所有随机分配的参与者都被纳入主要疗效和安全性分析。

People with lived experience of gout contributed to the study design and selection of outcome measures.

痛风患者的生活经验对研究设计和结果测量的选择做出了贡献。

The trial was registered with EudraCT, 2020-005721-82, and is closed to recruitment.

该试验已在EudraCT上注册，编号为2020-005721-82，并已停止招募。

Results

Between March 4, 2021, and Nov 4, 2022, 308 participants were randomly assigned, of whom 268 (87%) were male and 40 (13%) were female; the mean age was 65·93 years (SD 15·29).

从2021年3月4日到2022年11月4日，共有308名参与者被随机分配，其中268名（87%）为男性，40名（13%）为女性；平均年龄为65.93岁（标准差15.29）。

Participants were allocated to the treat-to-target group (145 participants) or the symptom-driven management group (163 participants).

参与者被分配到目标治疗组（145名参与者）或症状驱动管理组（163名参与者）。

Remission during months 18-24 occurred more often in the treat-to-target group than in the symptom-driven management group (39·4% [57 of 145 participants] vs 24·0% [39 of 163]; absolute difference 15·4 percentage points [95% CI 6·4-24·4]; p=0·024).

在第18至24个月期间，目标治疗组的缓解率高于症状驱动管理组（39·4% [57/145] vs 24·0% [39/163]；绝对差异15·4个百分点[95% CI 6·4-24·4]；p=0·024）。

Adverse events occurred in 61 (42%) participants in the treat-to-target group and 86 (53%) in the symptom-driven management group (absolute difference -10·7 percentage points [95% CI -21·8 to 0·4; p=0·060).

在目标治疗组中，有61名（42%）参与者出现不良事件，在症状驱动管理组中有86名（53%）出现不良事件（绝对差异为-10.7个百分点[95% 置信区间 -21.8至0.4; p=0.060]）。

No serious drug-related adverse events and no treatment-related deaths were reported.

没有报告任何严重的药物相关不良事件和治疗相关死亡。

interpretation

A treat-to-target strategy was associated with improved long-term disease control compared with symptom-driven care, without evidence of increased adverse events.

目标治疗策略与症状驱动的护理相比，与改善长期疾病控制相关，且没有不良事件增加的证据。

These findings provide support for the use of systematic serum urate-guided urate-lowering therapy titration in the routine management of gout.

这些发现为在痛风常规管理中使用系统性血尿酸指导的尿酸降低治疗滴定提供了支持。

funding

ZonMW and Reuma Nederland.

荷兰ZonMW和Reuma Nederland。