Supplementary Material for: Long-term outcome of ciclosporin and infliximab as rescue therapy in steroid-refractory acute severe ulcerative colitis

Background: Ciclosporin and infliximab have equal short-term efficacy in treating acute severe ulcerative colitis (ASUC). However, data about long-term outcome and switching to a second rescue therapy is limited.

Methods: Patients with steroid-refractory ASUC treated at a tertiary center in Switzerland were retrospectively analysed regarding the outcome of different rescue therapies. Colectomy-free survival rates at 1, 3 and 5 years were estimated through Kaplan-Meier method. Furthermore, predictors of colectomy, the presence of adverse events at 1 year and mortality during the entire follow-up were assessed.

Results: We analysed a total of 46 patients who were treated initially with either ciclosporin (n=31) or infliximab (n=15) due to steroid-refractory ASUC between January 2010 and July 2021. 13% of patients received a second rescue therapy. In sum, 78%, 67% and 48% were colectomy-free at 1, 3 and 5 years, respectively. Although there was a significant difference between the three arms in colectomy-free survival (p = 0.026), a post-hoc analysis could not demonstrate a difference between each individual therapy compared to another. The post-hoc analysis indicated a non-significant benefit with sequential therapy in comparison to CsA regarding the colectomy-free survival (p = 0.087). The outcome between infliximab and ciclosporin was not statistically different (p = 0.149). The number of previous advanced therapies was negatively associated with 1-year colectomy-free survival (p = 0.049). Other variables such as age at hospitalisation, sex, dose of steroids, disease duration and albumin did not correlate with a higher risk of 1-year colectomy.

Conclusions: This real-world single center analysis confirms the equal efficacy and safety of infliximab and ciclosporin over a follow-up of 5 years. Patients not responding to the first may benefit of a second rescue therapy without increasing the risk of complication or mortality.

背景：环孢素（Ciclosporin）与英夫利昔单抗（infliximab）治疗急性重症溃疡性结肠炎（acute severe ulcerative colitis, ASUC）的短期疗效相当，但关于长期转归以及换用第二种挽救治疗（rescue therapy）的相关数据仍较为有限。

方法：本研究对瑞士某三级医疗中心收治的激素难治性ASUC患者进行回顾性分析，以评估不同挽救治疗方案的转归情况。采用Kaplan-Meier法（Kaplan-Meier method）估算患者1年、3年及5年的无结肠切除术生存率。此外，本研究还评估了结肠切除术的预测因素、1年内不良事件发生情况以及整个随访周期内的死亡率。

结果：本研究共纳入2010年1月至2021年7月期间因激素难治性ASUC接受初始治疗的46例患者，其中31例接受环孢素治疗，15例接受英夫利昔单抗治疗。13%的患者后续接受了第二种挽救治疗。总体而言，患者1年、3年及5年的无结肠切除术生存率分别为78%、67%和48%。尽管三组的无结肠切除术生存率存在显著差异（P=0.026），但事后检验（post-hoc analysis）未能证明任意两种治疗方案之间存在显著差异。事后检验结果显示，与CsA（环孢素，Ciclosporin）相比，序贯治疗的无结肠切除术生存率有非显著性提升趋势（P=0.087）。英夫利昔单抗与环孢素的治疗转归无统计学差异（P=0.149）。既往接受过的高级别治疗次数与1年无结肠切除术生存率呈负相关（P=0.049）。其余变量，如住院时年龄、性别、糖皮质激素剂量、病程及血清白蛋白水平，均与1年结肠切除术风险升高无显著相关性。

结论：这项单中心真实世界研究证实，在5年随访周期内，英夫利昔单抗与环孢素的疗效及安全性相当。对初始治疗无应答的患者，可通过第二种挽救治疗获益，且不会增加并发症或死亡风险。