PDF(Pubmed)
Abstract：
BACKGROUND: The introduction of immune-checkpoint inhibitors (ICPI) in recent years has changed the natural course of many neoplasms. However, patients receiving these medications may present immune-mediated adverse events; management includes temporary or permanent cessation of treatment and corticosteroids, occasionally combined with other immunomodulators. Such immunosuppression, however, also has numerous adverse events and even if it is effective in controlling toxicity, it delays immunotherapy reinitiation, as current evidence requires dose tapering to ≤10 mg prednisolone equivalent before rechallenge. Enteric-coated budesonide is a corticosteroid formulation acting primarily to the intestine and liver, as a result of its extensive first-pass hepatic metabolism.
METHODS: A 76-year-old woman treated with ipilimumab for metastatic melanoma presented with abdominal pain, vomiting, and diarrhea for at least the previous 4 days. Laboratory tests, among others, revealed elevated aminotransferases and C-reactive protein. During hospitalization, the patient also developed fever.
METHODS: The patient, after excluding alternative causes of aminotransferase elevation, was diagnosed with grade 3 ipilimumab-associated hepatotoxicity.
METHODS: Budesonide monotherapy was administered; initial daily dose was 12 mg.
RESULTS: Fever subsided after the first dose of budesonide. Aminotransferases returned to normal-near normal approximately 1 month after the first dose of budesonide. After this point, daily dose was reduced by 3 mg every 2 weeks, with no clinical or biochemical relapse.
CONCLUSIONS: This case of ICPI hepatitis is, to our knowledge, the first in the literature managed with budesonide monotherapy. Therefore, budesonide may be a potentially attractive option for the management of ICPI-associated liver injury in cases where corticosteroid treatment is necessary due to its safety profile and the potential advantage of faster immunotherapy rechallenge in selected patients without requiring dose tapering, in contrast to systemically acting corticosteroids. Clinical trials should be conducted in the future in order to validate or refute these findings.
METHODS: A 76-year-old woman treated with ipilimumab for metastatic melanoma presented with abdominal pain, vomiting, and diarrhea for at least the previous 4 days. Laboratory tests, among others, revealed elevated aminotransferases and C-reactive protein. During hospitalization, the patient also developed fever.
METHODS: The patient, after excluding alternative causes of aminotransferase elevation, was diagnosed with grade 3 ipilimumab-associated hepatotoxicity.
METHODS: Budesonide monotherapy was administered; initial daily dose was 12 mg.
RESULTS: Fever subsided after the first dose of budesonide. Aminotransferases returned to normal-near normal approximately 1 month after the first dose of budesonide. After this point, daily dose was reduced by 3 mg every 2 weeks, with no clinical or biochemical relapse.
CONCLUSIONS: This case of ICPI hepatitis is, to our knowledge, the first in the literature managed with budesonide monotherapy. Therefore, budesonide may be a potentially attractive option for the management of ICPI-associated liver injury in cases where corticosteroid treatment is necessary due to its safety profile and the potential advantage of faster immunotherapy rechallenge in selected patients without requiring dose tapering, in contrast to systemically acting corticosteroids. Clinical trials should be conducted in the future in order to validate or refute these findings.
摘要：
背景：近年来免疫检查点抑制剂（ICPI）的引入改变了许多肿瘤的自然病程。然而,接受这些药物治疗的患者可能出现免疫介导的不良事件;管理包括暂时或永久停止治疗和皮质类固醇,偶尔与其他免疫调节剂联合使用。这种免疫抑制，然而,也有许多不良事件，即使它在控制毒性方面是有效的，它延迟了免疫疗法的重新启动，因为目前的证据要求在再次攻击前将剂量逐渐减少至相当于≤10mg泼尼松龙。肠溶布地奈德是一种主要作用于肠道和肝脏的皮质类固醇制剂，由于其广泛的首过肝代谢。
方法：一名76岁女性接受伊匹单抗治疗转移性黑色素瘤伴腹痛，呕吐,和腹泻至少前4天。实验室测试,其中,显示转氨酶和C反应蛋白升高。住院期间,病人也出现发烧。
方法：患者，在排除转氨酶升高的替代原因后，被诊断为3级ipilimumab相关肝毒性。
方法：布地奈德单药治疗；初始日剂量为12mg。
结果：首次服用布地奈德后发热消退。首次服用布地奈德后约1个月，氨基转移酶恢复正常-接近正常。在这之后,每日剂量每2周减少3毫克，没有临床或生化复发。
结论：该ICPI肝炎病例为，根据我们的知识，文献中第一个用布地奈德单药治疗。因此,布地奈德可能是治疗ICPI相关肝损伤的潜在有吸引力的选择，因为它的安全性和在选定的患者中更快的免疫疗法重新激发的潜在优势，而不需要剂量逐渐减少。与全身作用的皮质类固醇相反。将来应该进行临床试验，以验证或反驳这些发现。
方法：一名76岁女性接受伊匹单抗治疗转移性黑色素瘤伴腹痛，呕吐,和腹泻至少前4天。实验室测试,其中,显示转氨酶和C反应蛋白升高。住院期间,病人也出现发烧。
方法：患者，在排除转氨酶升高的替代原因后，被诊断为3级ipilimumab相关肝毒性。
方法：布地奈德单药治疗；初始日剂量为12mg。
结果：首次服用布地奈德后发热消退。首次服用布地奈德后约1个月，氨基转移酶恢复正常-接近正常。在这之后,每日剂量每2周减少3毫克，没有临床或生化复发。
结论：该ICPI肝炎病例为，根据我们的知识，文献中第一个用布地奈德单药治疗。因此,布地奈德可能是治疗ICPI相关肝损伤的潜在有吸引力的选择，因为它的安全性和在选定的患者中更快的免疫疗法重新激发的潜在优势，而不需要剂量逐渐减少。与全身作用的皮质类固醇相反。将来应该进行临床试验，以验证或反驳这些发现。
