Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, OH, U.S.A.
Ann Med. 2024 Dec;56(1):2358183. doi: 10.1080/07853890.2024.2358183. Epub 2024 May 30.
Real-world data on tofacitinib's effectiveness is limited and mainly retrospective or registry-based. We elected to conduct a pragmatic prospective study to assess the efficacy of tofacitinib for moderate to severe ulcerative colitis (UC), aiming to evaluate the ability of intestinal ultrasound (IUS) to discriminate responders vs. non-responders in real-time.
This pragmatic prospective clinical study included consecutive adult patients starting tofacitinib treatment for active moderate to severe UC. Patients were evaluated at baseline and after 8 weeks of tofacitinib (clinical, biomarker, endoscopy, and IUS). The primary outcome was clinical response defined by a decrease in the full Mayo score (fMS) of ≥3 at week 8. Next, we explored ultrasonographic parameters in the sigmoid colon as potential real-time classifiers to differentiate between responders and non-responders at week 8.
Overall, 30 adult patients started tofacitinib; the median age was 26.3 years (IQR 22.5-39.8), and 50% were female. Most patients (86.6%) had left-sided or extensive colitis, 96.7% had previously failed biologic therapy, and 60% (18/30) were on oral corticosteroids at the start of tofacitinib. At week 8, clinical response (a decrease in the fMS ≥ 3) and remission (fMS ≤ 2) rates were 40% (12/30) and 20% (6/30), respectively. Biomarker response (FC < 250µg/g) and biomarker normalization (FC ≤ 100µg/g) were achieved in 47.6% (10/21) and 38.1% (8/21) of patients, respectively. Endoscopic healing (endoscopic Mayo sub-score [EMS] ≤ 1) was achieved in 33.3% (10/30) of patients. Sigmoid bowel wall normalization as assessed by IUS (sBWT ≤ 3) was achieved in 18.2% (4/22). The best sBWT cut-off at week 8 to accurately classify endoscopic healing vs. no healing was a sBWT of 3.6 mm (AUC of 0.952 [95% CI: 0.868-1.036], < 0.001).
In this real-world pragmatic prospective study, tofacitinib was an effective treatment for moderate to severe UC, and IUS at week 8 accurately discriminated treatment response from non-response.
托法替布治疗溃疡性结肠炎（UC）的真实世界数据有限，主要为回顾性或基于登记的研究。我们选择进行一项实用的前瞻性研究，以评估托法替布治疗中重度 UC 的疗效，旨在实时评估肠道超声（IUS）区分应答者和无应答者的能力。
这项实用的前瞻性临床研究纳入了开始接受托法替布治疗的活动性中重度 UC 的连续成年患者。患者在基线和托法替布治疗 8 周后进行评估（临床、生物标志物、内镜和 IUS）。主要结局是 8 周时全 Mayo 评分（fMS）下降≥3 的临床应答。然后，我们探讨了乙状结肠的超声参数，作为区分 8 周时应答者和无应答者的潜在实时分类器。
共纳入 30 例成年患者接受托法替布治疗；中位年龄为 26.3 岁（IQR 22.5-39.8），50%为女性。大多数患者（86.6%）为左半结肠炎或广泛性结肠炎，96.7%曾接受过生物制剂治疗失败，60%（18/30）在开始托法替布治疗时接受口服皮质类固醇治疗。8 周时，临床应答（fMS 下降≥3）和缓解（fMS≤2）率分别为 40%（12/30）和 20%（6/30）。分别有 47.6%（10/21）和 38.1%（8/21）的患者达到生物标志物应答（FC＜250μg/g）和生物标志物正常化（FC≤100μg/g）。33.3%（10/30）的患者达到内镜愈合（内镜 Mayo 亚评分[EMS]≤1）。18.2%（4/22）的患者通过 IUS 评估乙状结肠壁正常化（sBWT≤3）。8 周时 sBWT 的最佳截断值为 3.6mm（AUC 为 0.952[95%CI：0.868-1.036]，<0.001），可准确区分内镜愈合与未愈合。
在这项真实世界的实用前瞻性研究中，托法替布是中重度 UC 的有效治疗方法，8 周时的 IUS 可准确区分治疗应答和无应答。
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