Bernardi Francesca, Faggiani Ilaria, Parigi Tommaso Lorenzo, Zilli Alessandra, Allocca Mariangela, Furfaro Federica, Peyrin-Biroulet Laurent, Danese Silvio, D'Amico Ferdinando
Gastroenterology and Endoscopy IRCCS, Ospedale San Raffaele, Via Olgettina 60, 20132 Milano, Italy.
Gastroenterology and Endoscopy, Vita Salute San Raffaele University, Via Olgettina 60, 20132 Milano, Italy.
Cancers (Basel). 2025 May 28;17(11):1795. doi: 10.3390/cancers17111795.
Janus kinase inhibitors, including tofacitinib, filgotinib, and upadacitinib, have emerged as effective therapeutic options for the management of inflammatory bowel diseases (IBDs). By targeting the JAK-STAT signaling pathway, these agents modulate immune responses and reduce inflammation. However, concerns regarding the potential risk of malignancy associated with their use have gained significant attention. The JAK-STAT pathway is not only critical for inflammatory signaling but also plays a pivotal role in cellular growth, differentiation, and tumor surveillance. Observational studies and clinical trial data in rheumatoid arthritis have reported malignancies, including non-melanoma skin cancer and solid tumors, in patients receiving JAK inhibitors, with evidence suggesting variable risks depending on the selectivity of the agent. Current evidence does not suggest an increased risk of oncogenesis in patients with IBDs. Balancing therapeutic efficacy with long-term safety requires ongoing vigilance; patient stratification based on risk factors; and tailored monitoring strategies to mitigate potential adverse effects, including malignancies, during JAK inhibitor therapy. Long-term follow-up data of up to 10 years offer reassuring evidence that JAK inhibitor therapy in IBD patients does not confer an increased risk of malignancies, supporting their continued use within appropriate clinical settings.
包括托法替布、非戈替尼和乌帕替尼在内的 Janus 激酶抑制剂已成为治疗炎症性肠病(IBD)的有效治疗选择。通过靶向 JAK-STAT 信号通路,这些药物可调节免疫反应并减轻炎症。然而,与其使用相关的潜在恶性肿瘤风险已引起广泛关注。JAK-STAT 通路不仅对炎症信号传导至关重要,而且在细胞生长、分化和肿瘤监测中也起着关键作用。类风湿关节炎的观察性研究和临床试验数据报告,接受 JAK 抑制剂治疗的患者出现了恶性肿瘤,包括非黑色素瘤皮肤癌和实体瘤,有证据表明风险因药物的选择性而异。目前的证据并不表明 IBD 患者的肿瘤发生风险增加。在长期安全性与治疗效果之间取得平衡需要持续保持警惕;根据风险因素对患者进行分层;并制定针对性的监测策略,以减轻 JAK 抑制剂治疗期间包括恶性肿瘤在内的潜在不良反应。长达 10 年的长期随访数据提供了令人安心的证据,即 IBD 患者接受 JAK 抑制剂治疗不会增加恶性肿瘤风险,支持在适当的临床环境中继续使用这些药物。