Xu Shuo, Chen Lu, Liu Kaixuan, Tao Hui, Ji Zhengzheng, Wu Jiamin, Zhao Yuanyi, Zhou Qiankun, Li Liuying, Zhu Hanlong, Wang Yunzhe, Wang Fangyu
Department of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
Department of Gastroenterology and Hepatology, Cangzhou People's Hospital, Cangzhou, Hebei, China.
Front Immunol. 2025 Aug 13;16:1627680. doi: 10.3389/fimmu.2025.1627680. eCollection 2025.
The risk of immune-related colitis (IRC) and efficacy of immune checkpoint inhibitors (ICIs) in patients with gastrointestinal cancers and preexisting ulcerative colitis (UC) has not been well described.
We divided the patients with gastrointestinal cancers and preexisting UC who received ICIs between January 2021 and May 2024 into two groups as IRC group and non-IRC group. The electronic medical records were reviewed to compare the risk of IRC between two groups. Survival analysis and COX regression was conducted to assess clinical efficacy.
Of the 138 patients in study, 31 patients had a history of UC prior to initiation of immunotherapy. IRC occurred in 22 patients (71.0%) and over half experienced severe IRC (54.5%), a rate higher than that among similar patients without underlying UC (17.4%, = 0.013). Compared with patients without UC who did not experience IRC, PFS and OS of patients with UC who had mild IRC were longer (PFS: 170 vs 96 days, < 0.001; OS: 261 vs 172 days, = 0.021) and those with severe IRC demonstrated merely a marginal advantage in terms of PFS (147 vs 96 days, = 0.001), but no significant difference was observed in OS (171 vs 172 days, = 0.851). The Multivariate analysis affirmed that mild IRC were correlated with a favorable prognosis (HR = 0.286, 95%CI: 0.106-0.769, = 0.013), whereas severe IRC was not sufficient to be recognized as independent risk factors affecting survival outcomes. (HR = 1.149, 95%CI: 0.502-2.633, = 0.742). The result of serum cytokines showed that the levels of IL-6 and IL-17A in patients with IRC were significantly elevated.
For preexisting UC patients treated with ICIs, the risk of IRC is increased. Mild IRC may suggest a favorable prognosis, and being vigilant and effectively managing the occurrence of severe IRC is crucial for maximizing clinical benefits. Targeting the IL-6 pathway may be a potential new strategy for treating IRC in the future.
免疫相关结肠炎（IRC）的风险以及免疫检查点抑制剂（ICI）在患有胃肠道癌症且已存在溃疡性结肠炎（UC）的患者中的疗效尚未得到充分描述。
我们将2021年1月至2024年5月期间接受ICI治疗的患有胃肠道癌症且已存在UC的患者分为两组，即IRC组和非IRC组。回顾电子病历以比较两组之间IRC的风险。进行生存分析和COX回归以评估临床疗效。
在138例研究患者中，31例在开始免疫治疗前有UC病史。22例患者发生IRC（71.0%），超过一半经历严重IRC（54.5%），这一发生率高于无潜在UC的类似患者（17.4%，P = 0.013）。与未发生IRC的无UC患者相比，患有轻度IRC的UC患者的无进展生存期（PFS）和总生存期（OS）更长（PFS：170天对96天，P < 0.001；OS：261天对172天，P = 0.021），而患有严重IRC的患者在PFS方面仅显示出微弱优势（147天对96天，P = 0.001），但在OS方面未观察到显著差异（171天对172天，P = 0.851）。多因素分析证实轻度IRC与良好预后相关（HR = 0.286，95%CI：0.106 - 0.769，P = 0.013），而严重IRC不足以被视为影响生存结果的独立危险因素（HR = 1.149，95%CI：0.502 - 2.633，P = 0.742）。血清细胞因子结果显示，IRC患者的IL - 6和IL - 17A水平显著升高。
对于接受ICI治疗的已存在UC的患者，IRC风险增加。轻度IRC可能提示良好预后，警惕并有效管理严重IRC的发生对于最大化临床获益至关重要。靶向IL - 6途径可能是未来治疗IRC的一种潜在新策略。
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