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JAK 抑制剂乌帕替尼诱导恶性胸膜间皮瘤中 CTLA-4 和 PD-1 抑制剂联合治疗引发难治性免疫相关性结肠炎缓解:病例报告。

JAK Inhibitor Upadacitinib Induces Remission in Refractory Immune-Related Colitis Triggered by CTLA-4 and PD-1 Inhibitor Combination Therapy in Malignant Pleural Mesothelioma: A Case Report.

机构信息

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.

Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan.

出版信息

Cancer Rep (Hoboken). 2024 Oct;7(10):e70032. doi: 10.1002/cnr2.70032.

Abstract

BACKGROUND

Immune checkpoint inhibitors have demonstrated efficacy against various cancers; however, there is a rising incidence of immune-related colitis. Some cases of immune-related colitis prove resistant to treatment, even with the administration of glucocorticoids or infliximab, and there is currently no established standard treatment for such cases.

CASE

The patient, a 73-year-old male, had undergone combination therapy for malignant pleural mesothelioma for 2 years, utilizing both ipilimumab (a CTLA-4 inhibitor) and nivolumab (a PD-1 inhibitor). Unfortunately, the treatment led to side effects, specifically immune-related adverse event (irAE) enterocolitis. Steroid and infliximab treatment failed to improve the patient's condition. Treatment with tacrolimus was attempted, but the patient remained unresponsive. Subsequently, 45 mg of upadacitinib, a Janus kinase (JAK) inhibitor, was administered. Symptoms improved rapidly following upadacitinib administration, and endoscopy also revealed positive results. With the increasing incidence of immune-related colitis, some patients have become resistant to treatment with glucocorticoids and infliximab. In this case, the irAE enterocolitis was improved by upadacitinib administration.

CONCLUSION

In cases where immune-related colitis proves resistant to treatment with glucocorticoids, infliximab, or tacrolimus, upadacitinib represents a potential option as a JAK inhibitor.

摘要

背景

免疫检查点抑制剂已被证明对各种癌症有效;然而,免疫相关性结肠炎的发病率正在上升。一些免疫相关性结肠炎病例对治疗有抗药性,即使使用糖皮质激素或英夫利昔单抗治疗也是如此,目前对此类病例尚无既定的标准治疗方法。

病例

患者为 73 岁男性,因恶性胸膜间皮瘤接受了 2 年的联合治疗,使用了伊匹单抗(一种 CTLA-4 抑制剂)和纳武利尤单抗(一种 PD-1 抑制剂)。不幸的是,治疗导致了副作用,特别是免疫相关不良事件(irAE)结肠炎。类固醇和英夫利昔单抗治疗未能改善患者的病情。尝试使用他克莫司治疗,但患者仍无反应。随后,给予 45mg 巴瑞替尼,一种 Janus 激酶(JAK)抑制剂。给予巴瑞替尼后症状迅速改善,内镜检查也显示出阳性结果。随着免疫相关性结肠炎的发病率不断上升,一些患者对糖皮质激素和英夫利昔单抗的治疗产生了抗药性。在这种情况下,irAE 结肠炎通过给予巴瑞替尼得到了改善。

结论

对于糖皮质激素、英夫利昔单抗或他克莫司治疗无效的免疫相关性结肠炎病例,巴瑞替尼作为一种 JAK 抑制剂可能是一种潜在的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26af/11518693/aee6a49a8dda/CNR2-7-e70032-g002.jpg

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