难治性炎症性肠病中JAK1的优先抑制：将upadactinib重新定义为快速免疫重新校准的策略
JAK1-preferential inhibition in refractory inflammatory bowel disease: reframing upadacitinib as a strategy for rapid immune recalibration.
摘要(中文译文)
炎症性肠病（IBD）的管理已从症状控制转向达标治疗策略，然而许多溃疡性结肠炎或克罗恩病患者在原发性无应答、继发性失应答或对高级治疗不耐受后仍难以治疗。Upadacitinib是一种口服Janus激酶1（JAK1）偏好性抑制剂，在溃疡性结肠炎和克罗恩病中均显示出具有临床意义的疗效，包括生物制剂经治人群。在本视角文章中，我们提出“快速免疫重校准”作为一个产生假设的临床模型，用于解读部分以炎症为主的难治性IBD患者在接受JAK1偏好性抑制后出现的快速炎症控制，而非将其视为已确立的生物学机制或持久免疫重置的证据。此处的重校准定义为早期药物诱导的汇聚性细胞因子信号强度与平衡的改变，而非免疫稳态恢复、黏膜愈合、透壁修复、纤维化逆转或已证实的疾病修饰。我们区分了已确立的临床证据、机制学原理与未经证实的下游假设，后者包括屏障稳定、微生物组改变、抗纤维化潜力及生物标志物指导下的定位。我们还概述了可测量的临床标准、可行的生物标志物、探索性转化终点及安全性边界，以指导未来对该框架的检验。这种更为有限度的解读可能有助于为未来努力提供信息，推动难治性IBD治疗从经验性换药转向机制指导下的治疗选择，同时避免夸大现有证据。
Abstract
Inflammatory bowel disease (IBD) management has moved from symptom control toward treat-to-target strategies, yet many patients with ulcerative colitis or Crohn's disease remain difficult to treat after primary non-response, secondary loss of response, or intolerance to advanced therapy. Upadacitinib, an oral Janus kinase 1 (JAK1)-preferential inhibitor, has shown clinically meaningful efficacy in both ulcerative colitis and Crohn's disease, including biologic-experienced populations. In this Perspective, we propose rapid immune recalibration as a hypothesis-generating clinical model for interpreting rapid inflammatory control following JAK1-preferential inhibition in selected patients with inflammation-dominant refractory IBD, rather than as an established biological mechanism or evidence of a durable immune reset. Recalibration is defined here as an early pharmacologically induced shift in the intensity and balance of convergent cytokine signaling, not as immune homeostasis restoration, mucosal healing, transmural repair, fibrosis reversal, or proven disease modification. We distinguish established clinical evidence from mechanistic rationale and from unvalidated downstream hypotheses, including barrier stabilization, microbiome change, anti-fibrotic potential, and biomarker-guided positioning. We also outline measurable clinical criteria, feasible biomarkers, exploratory translational endpoints, and safety boundaries that should guide future testing of this framework. This more bounded interpretation may help inform future efforts to move refractory IBD treatment from empirical drug switching toward mechanism-informed therapeutic choice without overstating the current evidence.
如何引用
AMA
Xiaowei Liu, Yang Wang. JAK1-preferential inhibition in refractory inflammatory bowel disease: reframing upadacitinib as a strategy for rapid immune recalibration.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1893892.
APA
Xiaowei Liu, Yang Wang (2026). JAK1-preferential inhibition in refractory inflammatory bowel disease: reframing upadacitinib as a strategy for rapid immune recalibration.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1893892
GB/T 7714
Xiaowei Liu, Yang Wang. JAK1-preferential inhibition in refractory inflammatory bowel disease: reframing upadacitinib as a strategy for rapid immune recalibration.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1893892.
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