Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Radiology, UMC Utrecht, Utrecht, The Netherlands.
BMJ Open. 2022 Oct 10;12(10):e064338. doi: 10.1136/bmjopen-2022-064338.
Psoriatic arthritis (PsA) is a chronic, inflammatory, musculoskeletal disease that affects up to 30% of patients with psoriasis. Current challenges in clinical care and research include personalised treatment, understanding the divergence of therapy response and unravelling the multifactorial pathophysiology of this complex disease. Moreover, there is an urgent clinical need to predict, assess and understand the cellular and molecular pathways underlying the response to disease-modifying antirheumatic drugs (DMARDs). The TOFA-PREDICT clinical trial addresses this need. Our primary objective is to determine key immunological factors predicting tofacitinib efficacy and drug-free remission in PsA.
In this investigator-initiated, phase III, multicentre, open-label, four-arm randomised controlled trial, we plan to integrate clinical, molecular and imaging parameters of 160 patients with PsA. DMARD-naïve patients are randomised to methotrexate or tofacitinib. Additionally, patients who are non-responsive to conventional synthetic (cs)DMARDs continue their current csDMARD and are randomised to etanercept or tofacitinib. This results in four arms each with 40 patients. Patients are followed for 1 year. Treatment response is defined as minimal disease activity at week 16. Clinical data, biosamples and images are collected at baseline, 4 weeks and 16 weeks; at treatment failure (treatment switch) and 52 weeks. For the first 80 patients, we will use a systems medicine approach to assess multiomics biomarkers and develop a prediction model for treatment response. Subsequently, data from the second 80 patients will be used for validation.
The study was approved by the Medical Research Ethics Committee in Utrecht, Netherlands, is registered in the European Clinical Trials Database and is carried out in accordance with the Declaration of Helsinki. The study's progress is monitored by Julius Clinical, a science-driven contract research organisation.
EudraCT: 2017-003900-28.
银屑病关节炎（PsA）是一种慢性、炎症性、肌肉骨骼疾病，可影响多达 30%的银屑病患者。目前临床治疗和研究中的挑战包括个体化治疗、了解治疗反应的差异以及阐明这种复杂疾病的多因素病理生理学。此外，迫切需要预测、评估和了解疾病修饰抗风湿药物（DMARDs）反应背后的细胞和分子途径。TOFA-PREDICT 临床试验满足了这一需求。我们的主要目标是确定预测托法替尼治疗银屑病关节炎疗效和无药物缓解的关键免疫学因素。
在这项由研究者发起的、III 期、多中心、开放性、四臂随机对照试验中，我们计划整合 160 例银屑病关节炎患者的临床、分子和影像学参数。初治 DMARD 患者随机分为甲氨蝶呤或托法替尼组。此外，对常规合成 DMARD 反应不佳的患者继续使用当前的 csDMARD，并随机分为依那西普或托法替尼组。这导致每个组各有 40 例患者。患者随访 1 年。治疗反应定义为第 16 周时疾病活动度最小。临床数据、生物样本和图像在基线、4 周和 16 周；在治疗失败（治疗转换）和 52 周时采集。对于前 80 例患者，我们将使用系统医学方法评估多组学生物标志物并开发治疗反应预测模型。随后，将使用第 80 例后 80 例患者的数据进行验证。
该研究得到荷兰乌得勒支医学研究伦理委员会的批准，在欧洲临床试验数据库注册，并按照赫尔辛基宣言进行。该研究的进展由 Julius Clinical（一家以科学为驱动的合同研究组织）监测。
EudraCT：2017-003900-28。
