Background Few small studies have assessed the efficacy of topical therapy with tacrolimus in patients with ulcerative colitis (UC). The aim of our study was to evaluate its effectiveness and safety in a real-world setting. Methods A multicenter observational retrospective study at 25 Spanish GETECCU hospitals was performed. Adult patients with UC who received topical tacrolimus from January 2009 to January 2023 were eligible. Inclusion criteria were proctitis, left-sided, or extensive colitis with persistent distal colonic activity confirmed endoscopically during the previous 3 months. Clinical and biochemical data were collected at baseline, week 4, 8 and 54. Tacrolimus trough levels were evaluated in week 4 and 8. Primary outcome was clinical response at week 8, defined as a ≥3 points or ≥30% decrease of partial Mayo score with ≥1point reduction in the bleeding score. Mean partial mayo scores were compared using the t-test. A p<0.05 was considered statistically significant. Results 106 patients, 59 (55.6%) males, median age 48.7 years (IQR:39.9-59.7), received rectal tacrolimus during a median of 9.7 weeks (IQR:5-18.7). Sixty-four patients (60.4%) received suppositories, 41 (38.7%) enemas and 1 patient an ointment (0.9%). Thirty (28.3%) were patients with proctitis, 45 (42.4%) with left colitis and 31 (29.2%) with extensive colitis. At baseline, 54 patients (50.9%) received concomitant biological/small molecules therapy, while 14 patients received immunomodulators. Most common dose was 2 mg (84%) Q24H (71.7%). A significant decrease in mean partial mayo score was observed at week 4 and 8 (figure 1). Clinical response at week 8 was achieved in 63 patients (66.3%) and clinical remission in 42 (44.2%). 32 patients (33.7%) were non-responder at week 8. Clinical response and remission at week 4 were achieved in 56 (57.7%) and 33 (34.4%), respectively. Clinical response at week 8 was similar between the group with concomitant biological therapy and without (64.6.9% vs 68.1%, p=0.8). Clinical response at week 8 was similar among different extensions (proctitis: 55.6%; left colitis: 80%; extensive colitis 57.1%; p=0.052). Clinical outcomes are detailed in table 1. Median tacrolimus trough levels at week 4 was 3.4 ng/ml (IQR 1.5-6.7) and 2.9 ng/ml (IQR 1.5-6) at week 8. Adverse events were detected in 21 patients (19.8%), Thirteen were graded as mild and 8 moderate. Treatment was ceased due to adverse events in 11 (10.4%) patients. Conclusion Topical tacrolimus is effective in UC achieving clinical response in more than sixty percent at week 8 with even lower doses than reported in clinical trials. Adverse events reported in nearly 20% of patients were mostly mild.

中文翻译：

---

P949 直肠他克莫司治疗溃疡性结肠炎患者的有效性和安全性。TACRO-TOPIC 研究。GETECCU青年组多中心研究

背景 很少有小型研究评估他克莫司局部治疗对溃疡性结肠炎 (UC) 患者的疗效。我们研究的目的是评估其在现实环境中的有效性和安全性。方法 在西班牙 25 家 GETECCU 医院进行多中心观察性回顾性研究。2009 年 1 月至 2023 年 1 月期间接受局部他克莫司治疗的成年 UC 患者符合资格。纳入标准为直肠炎、左侧结肠炎或广泛性结肠炎，且在过去 3 个月内经内镜检查证实存在持续性远端结肠活动。在基线、第 4、8 和 54 周收集临床和生化数据。在第 4 周和第 8 周评估他克莫司谷水平。主要结局是第 8 周的临床反应，定义为部分 Mayo 降低 ≥3 分或 ≥30%出血评分减少≥1分。使用 t 检验比较平均部分 Mayo 分数。p＜0.05被认为具有统计显着性。结果 106 名患者，59 名（55.6%）男性，中位年龄 48.7 岁（IQR：39.9-59.7），接受直肠他克莫司治疗，中位时间为 9.7 周（IQR：5-18.7）。64 名患者 (60.4%) 接受栓剂治疗，41 名患者 (38.7%) 接受灌肠剂治疗，1 名患者接受软膏治疗 (0.9%)。直肠炎 30 例（28.3%），左侧结肠炎 45 例（42.4%），广泛性结肠炎 31 例（29.2%）。基线时，54 名患者 (50.9%) 接受了联合生物/小分子治疗，而 14 名患者接受了免疫调节剂。最常见的剂量是 2 mg (84%) Q24H (71.7%)。第 4 周和第 8 周观察到平均部分 Mayo 评分显着下降（图 1）。第 8 周时，63 名患者（66.3%）获得临床缓解，42 名患者（44.2%）获得临床缓解。第 8 周时，有 32 名患者 (33.7%) 无反应。第 4 周时，分别有 56 名患者 (57.7%) 和 33 名患者 (34.4%) 达到临床反应和缓解。第 8 周时，同时进行生物治疗和不进行生物治疗的组的临床反应相似（64.6.9% vs 68.1%，p=0.8）。第 8 周时，不同延伸范围的临床反应相似（直肠炎：55.6%；左侧结肠炎：80%；广泛性结肠炎 57.1%；p=0.052）。临床结果详见表 1。第 4 周时他克莫司谷值中位数为 3.4 ng/ml (IQR 1.5-6.7)，第 8 周时为 2.9 ng/ml (IQR 1.5-6)。21 名患者 (19.8 %)，13 例被评为轻度，8 例为中度。11 名患者 (10.4%) 因不良事件而停止治疗。结论 外用他克莫司可有效治疗 UC，第 8 周时达到 60% 以上的临床缓解，剂量甚至低于临床试验报告的剂量。近 20% 的患者报告的不良事件大多是轻微的。