难治性克罗恩病的联合治疗的研究进展

Research Progress on Combined Therapy for Refractory Crohn’s Disease

摘要: 难治性克罗恩病(CD)是指对现有生物制剂及小分子药物反应不足或无效的疾病亚型，其发生与多重炎症通路激活、免疫细胞异常(如AQP9 + 巨噬细胞扩增)及信号通路失调(如gp130-STAT3轴)密切相关。联合治疗通过协同靶向不同机制(如双生物制剂、生物制剂联合小分子药物)突破单一疗法的疗效瓶颈，在难治性患者中展现出显著临床潜力。研究显示，联合方案(如upadacitinib联合infliximab)可使多数患者获得短期临床应答，部分实现无激素缓解。然而，其临床应用仍面临个体疗效差异、安全性风险(如感染、输液反应)及缺乏精准生物标志物等挑战。未来需聚焦机制探索、个体化策略优化及多模态整合(如干细胞疗法、营养干预)，以提升难治性CD的治疗效果与生存质量。

Abstract: Refractory Crohn’s disease (CD) refers to a disease subtype that shows insufficient or no response to existing biologics and small molecule drugs. Its occurrence is closely related to the activation of multiple inflammatory pathways, abnormal immune cells (such as the expansion of AQP9 + macrophages), and dysregulation of signaling pathways (such as the gp130-STAT3 axis). Combination therapy, by synergistically targeting different mechanisms (such as dual biologics or biologics combined with small molecule drugs), has broken through the efficacy bottleneck of single therapy and demonstrated significant clinical potential in refractory patients. Studies have shown that combination regimens (such as upadacitinib combined with infliximab) can lead to short-term clinical responses in most patients and achieve steroid-free remission in some. However, its clinical application still faces challenges such as individual efficacy differences, safety risks (such as infections and infusion reactions), and the lack of precise biomarkers. In the future, efforts should focus on mechanism exploration, optimization of individualized strategies, and multi-modal integration (such as stem cell therapy and nutritional intervention) to improve the treatment outcomes and quality of life for refractory CD patients.