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Abstract：
BACKGROUND: Current treatment guidelines for moderate to severe colitis (IMC) secondary to immune checkpoint inhibitors (ICI) recommend systemic corticosteroids as the primary therapy in conjunction with biologics, namely infliximab and/or vedolizumab. We aimed to explore the efficacy and safety of oral budesonide in the treatment of IMC.
METHODS: We performed a retrospective analysis at MD Anderson Cancer Center of adult cancer patients with a confirmed (based on clinical, radiographic and laboratory assessment) diagnosis of IMC between 1 January 2015 and 31 November 2022, treated with budesonide. Data collection included demographics, oncologic history, IMC-related information and outcomes up to 6 months after the last dose of ICI.
RESULTS: Our sample (n = 69) comprised primarily of Caucasian (76.8%) females (55.1%). The majority of patients received combination therapy with anti-PD-1/L1 and anti-CTLA-4 (49.3%), and the most common malignancy treated was melanoma (37.6%). The median grade of diarrhea was 3 and of colitis was 2. Of the 50 patients who underwent endoscopic evaluation, a majority had non-ulcerative inflammation (64%) and active colitis on histology (78%). Budesonide was used as primary treatment at onset of IMC in 56.5% patients, as well as a bridging therapy from systemic corticosteroids in 33.3%. Less than half of the patients (44.9%) required additional therapies such as biologics or fecal microbiota transplant. Additionally, 75.3% of patients achieved full remission of IMC and 24.6% had a recurrence of IMC. ICI was resumed in 31.9% of patients and 17.4% received other forms of cancer therapies.
CONCLUSIONS: Budesonide may be an effective strategy to treat and prevent the recurrence of IMC. The remission rates observed in our analysis with budesonide alone are comparable to systemic corticosteroids. Patients that require an extended duration of steroid exposure and those with moderate to severe colitis may benefit from budesonide given its lower risk of infection and complications. Furthermore, we observe that budesonide may serve as a successful bridge from systemic corticosteroids with subsequent biologic treatment. Larger prospective studies are necessary to determine the role of budesonide as well as its safety profile.
METHODS: We performed a retrospective analysis at MD Anderson Cancer Center of adult cancer patients with a confirmed (based on clinical, radiographic and laboratory assessment) diagnosis of IMC between 1 January 2015 and 31 November 2022, treated with budesonide. Data collection included demographics, oncologic history, IMC-related information and outcomes up to 6 months after the last dose of ICI.
RESULTS: Our sample (n = 69) comprised primarily of Caucasian (76.8%) females (55.1%). The majority of patients received combination therapy with anti-PD-1/L1 and anti-CTLA-4 (49.3%), and the most common malignancy treated was melanoma (37.6%). The median grade of diarrhea was 3 and of colitis was 2. Of the 50 patients who underwent endoscopic evaluation, a majority had non-ulcerative inflammation (64%) and active colitis on histology (78%). Budesonide was used as primary treatment at onset of IMC in 56.5% patients, as well as a bridging therapy from systemic corticosteroids in 33.3%. Less than half of the patients (44.9%) required additional therapies such as biologics or fecal microbiota transplant. Additionally, 75.3% of patients achieved full remission of IMC and 24.6% had a recurrence of IMC. ICI was resumed in 31.9% of patients and 17.4% received other forms of cancer therapies.
CONCLUSIONS: Budesonide may be an effective strategy to treat and prevent the recurrence of IMC. The remission rates observed in our analysis with budesonide alone are comparable to systemic corticosteroids. Patients that require an extended duration of steroid exposure and those with moderate to severe colitis may benefit from budesonide given its lower risk of infection and complications. Furthermore, we observe that budesonide may serve as a successful bridge from systemic corticosteroids with subsequent biologic treatment. Larger prospective studies are necessary to determine the role of budesonide as well as its safety profile.
摘要：
背景：目前针对免疫检查点抑制剂（ICI）继发的中度至重度结肠炎（IMC）的治疗指南推荐全身性皮质类固醇作为与生物制剂结合的主要治疗方法，即英夫利昔单抗和/或维多珠单抗。目的探讨口服布地奈德治疗IMC的疗效和安全性。
方法：我们在MDAnderson癌症中心对成年癌症患者进行了回顾性分析，其中证实了（基于临床，放射学和实验室评估）2015年1月1日至2022年11月31日之间的IMC诊断，用布地奈德治疗。数据收集包括人口统计，肿瘤病史,与IMC相关的信息和结果，直到最后一次ICI剂量后6个月。
结果:我们的样本(n=69)主要包括白种人(76.8%)女性(55.1%)。大多数患者接受抗PD-1/L1和抗CTLA-4联合治疗（49.3%），最常见的恶性肿瘤是黑色素瘤(37.6%).腹泻的中位数为3级，结肠炎的中位数为2级。在50例接受内镜检查的患者中，大多数患者在组织学上有非溃疡性炎症(64%)和活动性结肠炎(78%).56.5％的患者在IMC发作时使用布地奈德作为主要治疗方法，以及33.3％的全身性皮质类固醇的桥接治疗。不到一半的患者（44.9%）需要其他治疗，如生物制剂或粪便微生物移植。此外,75.3％的患者IMC完全缓解，24.6％的患者IMC复发。31.9％的患者恢复了ICI，17.4％的患者接受了其他形式的癌症治疗。
结论：布地奈德可能是治疗和预防IMC复发的有效策略。在我们的分析中观察到的单独使用布地奈德的缓解率与全身性皮质类固醇相当。需要延长类固醇暴露持续时间的患者和中度至重度结肠炎患者可能受益于布地奈德，因为布地奈德的感染和并发症风险较低。此外，我们观察到,布地奈德可能是全身性糖皮质激素与后续生物治疗的成功桥梁.需要更大规模的前瞻性研究来确定布地奈德的作用及其安全性。
方法：我们在MDAnderson癌症中心对成年癌症患者进行了回顾性分析，其中证实了（基于临床，放射学和实验室评估）2015年1月1日至2022年11月31日之间的IMC诊断，用布地奈德治疗。数据收集包括人口统计，肿瘤病史,与IMC相关的信息和结果，直到最后一次ICI剂量后6个月。
结果:我们的样本(n=69)主要包括白种人(76.8%)女性(55.1%)。大多数患者接受抗PD-1/L1和抗CTLA-4联合治疗（49.3%），最常见的恶性肿瘤是黑色素瘤(37.6%).腹泻的中位数为3级，结肠炎的中位数为2级。在50例接受内镜检查的患者中，大多数患者在组织学上有非溃疡性炎症(64%)和活动性结肠炎(78%).56.5％的患者在IMC发作时使用布地奈德作为主要治疗方法，以及33.3％的全身性皮质类固醇的桥接治疗。不到一半的患者（44.9%）需要其他治疗，如生物制剂或粪便微生物移植。此外,75.3％的患者IMC完全缓解，24.6％的患者IMC复发。31.9％的患者恢复了ICI，17.4％的患者接受了其他形式的癌症治疗。
结论：布地奈德可能是治疗和预防IMC复发的有效策略。在我们的分析中观察到的单独使用布地奈德的缓解率与全身性皮质类固醇相当。需要延长类固醇暴露持续时间的患者和中度至重度结肠炎患者可能受益于布地奈德，因为布地奈德的感染和并发症风险较低。此外，我们观察到,布地奈德可能是全身性糖皮质激素与后续生物治疗的成功桥梁.需要更大规模的前瞻性研究来确定布地奈德的作用及其安全性。
