Rejler Martin, Füchtbauer Johannes David, Davíðsdóttir Lóa G, Fejrskov Anja, Söderholm Johan D, Christensen Robin, Andersen Vibeke, Repsilber Dirk, Kjeldsen Jens, Høivik Marte, Halfvarson Jonas
School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
Futurum Academy of Health and Care, Jönköping, Sweden.
BMJ Open. 2024 Jul 31;14(7):e083163. doi: 10.1136/bmjopen-2023-083163.
The absence of reliable prognostic markers poses a challenge to the management of inflammatory bowel disease (IBD). Patients with aggressive disease may not receive sufficient treatment with conventional 'step-up' therapy, whereas a top-down approach may expose patients with indolent disease to unnecessary treatment-related toxicity. The objective of the Nordic IBD treatment strategy trial (NORDTREAT) is to assess the feasibility of personalised therapy by stratifying patients according to a prognostic serum protein signature at diagnosis.
NORDTREAT is a multicentre, biomarker-strategy design, open-label controlled trial. After screening consent, eligible patients are randomised (1:1) into one of two groups: a group with access to the protein signature and a group without access. In the access to protein signature group, patients displaying a protein signature suggestive of an increased risk of an aggressive disease course will be treated in line with a top-down treatment algorithm (anti-tumour necrosis factor agent with/without an immunomodulator). In contrast, those with a protein signature indicative of indolent disease will be excluded from the trial. Patients not in the access group receive treatment based on clinical management. This traditional management involves a stepwise escalation of treatment as determined by the investigator after failure of first-line treatment. After 52 weeks, outcomes are assessed in the subgroup of patients with a protein profile indicating a potentially severe disease trajectory. The primary endpoint is a composite of the proportion of patients with corticosteroid-free clinical and endoscopic remission at week 52. Surgical intervention due to IBD during follow-up will be defined as treatment failure.
Ethical approval has been obtained, and recruitment is underway at sites in four participating Nordic countries (Denmark, Iceland, Norway and Sweden). Following trial completion and data analysis, the trial results will be submitted for publication in peer-reviewed journals and presented at international conferences.
NCT05180175; Pre-results. EudraCT number: 2019-002942-19.
缺乏可靠的预后标志物对炎症性肠病（IBD）的管理构成了挑战。患有侵袭性疾病的患者可能无法通过传统的“逐步升级”疗法获得充分治疗，而自上而下的治疗方法可能会使患有惰性疾病的患者面临不必要的治疗相关毒性。北欧IBD治疗策略试验（NORDTREAT）的目的是通过在诊断时根据预后血清蛋白特征对患者进行分层来评估个性化治疗的可行性。
NORDTREAT是一项多中心、生物标志物策略设计的开放标签对照试验。在筛选同意后，符合条件的患者被随机（1:1）分为两组：一组可以获取蛋白特征，另一组无法获取。在可以获取蛋白特征的组中，显示出提示侵袭性病程风险增加的蛋白特征的患者将按照自上而下的治疗方案（使用/不使用免疫调节剂的抗肿瘤坏死因子药物）进行治疗。相比之下，那些具有提示惰性疾病的蛋白特征的患者将被排除在试验之外。不在获取组的患者根据临床管理接受治疗。这种传统管理涉及在一线治疗失败后由研究者确定的逐步升级治疗。52周后，在具有表明潜在严重疾病轨迹的蛋白谱的患者亚组中评估结果。主要终点是第52周时无皮质类固醇临床和内镜缓解的患者比例的综合指标。随访期间因IBD进行的手术干预将被定义为治疗失败。
已获得伦理批准，正在四个参与的北欧国家（丹麦、冰岛、挪威和瑞典）的地点进行招募。试验完成和数据分析后，试验结果将提交至同行评审期刊发表，并在国际会议上展示。
NCT05180175；预结果。欧盟临床试验注册号：2019-002942-19。
