University of North Carolina at Chapel Hill, Division of Gastroenterology and Hepatology, Chapel Hill, NC, USA.
Ohio State University, Division of Gastroenterology and Hepatology, Columbus, OH, USA.
Inflamm Bowel Dis. 2023 Apr 3;29(4):570-578. doi: 10.1093/ibd/izac121.
Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Using a novel electronic reporting tool, we aimed to prospectively describe the onset of tofacitinib efficacy during induction therapy in a real-world study.
Patient-reported outcome data (PROs) including the simple clinical colitis activity index (SCCAI), PRO Measurement Identification Systems (PROMIS) measures, and adverse events were collected daily for the first 14 days and at day 28 and 56. Paired t tests and P for trend were utilized to compare changes in SCCAI over time. Bivariate analyses and logistic regression models were performed to describe response (SCCAI <5) and remission (SCCAI ≤2) by clinical factors.
Of all included patients (n = 96), 67% had failed ≥2 biologics, and 61.5% were on concomitant steroids. Starting at day 3, PROs showed significant and persistent decline of the mean SCCAI (-1.1, P < 000.1) including significantly lower SCCAI subscores for stool frequency (-0.3; P < .003), bleeding (-0.3; P < .0002) and urgency (-0.2; P < .001). Steroid-free remission at day 14, 28, and 56 was achieved in 25%, 30.2%, and 29.2% of patients, respectively. Neither prior biologics nor endoscopic severity were independently predictive of response or remission in multivariate models. Numeric improvements in all PROMIS measures (anxiety, depression, social satisfaction) were seen through day 56. Rates of discontinuation due to adverse events were low.
In this prospective real-world study, tofacitinib resulted in a rapid and persistent improvement in UC disease activity PROs. The safety findings were consistent with the established safety profile of tofacitinib.
托法替尼是一种用于治疗溃疡性结肠炎（UC）的口服小分子 JAK 抑制剂。我们使用一种新的电子报告工具，旨在前瞻性描述在真实世界研究中诱导治疗期间托法替尼疗效的出现。
患者报告的结局数据（PROs）包括简单临床结肠炎活动指数（SCCAI）、PRO 测量识别系统（PROMIS）测量值和不良事件，在第 14 天和第 28 天和第 56 天每天收集。采用配对 t 检验和趋势 P 值比较 SCCAI 随时间的变化。采用双变量分析和逻辑回归模型描述临床因素对反应（SCCAI <5）和缓解（SCCAI ≤2）的影响。
所有纳入患者（n=96）中，67%的患者曾使用过≥2 种生物制剂治疗失败，61.5%的患者同时使用类固醇。从第 3 天开始，PROs 显示出 SCCAI 的显著和持续下降（-1.1，P < 0.001），包括粪便频率（-0.3；P < 0.03）、出血（-0.3；P < 0.0002）和急迫感（-0.2；P < 0.001）的 SCCAI 亚评分显著降低。第 14、28 和 56 天无类固醇缓解的患者分别占 25%、30.2%和 29.2%。在多变量模型中，既往生物制剂或内镜严重程度均不能独立预测反应或缓解。所有 PROMIS 测量值（焦虑、抑郁、社会满意度）在第 56 天均有数值改善。因不良事件而停药的发生率较低。
在这项前瞻性真实世界研究中，托法替尼迅速并持续改善 UC 疾病活动 PROs。安全性发现与托法替尼既定的安全性特征一致。
