Preexisting Ulcerative Colitis Increases the Risk of Immune-Related Colitis and Predicts Divergent Survival Outcomes in Gastrointestinal Cancer Patients Treated with Immune Checkpoint Inhibitors

Shuo Xu¹Lu Chen¹Kaixuan Liu²Hui Tao¹ZhengZheng Ji³Jiamin Wu¹Yuanyi Zhao⁴Qiankun Zhou¹Liuying Li¹Hanlong Zhu^1*Yunzhe Wang^3*Fangyu Wang^1*

• ¹Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
• ²Cangzhou People's Hospital, Cangzhou, China
• ³The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
• ⁴Jinling Hospital, Nanjing Medical University, Nanjing, China

Background: 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. Patients and methods: 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. Results: 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%, p = 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, p < 0.001; OS: 261 vs 172 days, p = 0.021) and those with severe IRC demonstrated merely a marginal advantage in terms of PFS (147 vs 96 days, p = 0.001), but no significant difference was observed in OS (171 vs 172 days, p = 0.851). The Multivariate analysis affirmed that mild IRC were correlated with a favorable prognosis (HR = 0.286, 95%CI: 0.106-0.769, p = 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, p = 0.742). The result of serum cytokines showed that the levels of IL-6 and IL-17A in patients with IRC were significantly elevated. Conclusion: 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.