Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
Division of Gastroenterology, Northwestern University, Chicago, Illinois.
Clin Gastroenterol Hepatol. 2023 Dec;21(13):3387-3396.e1. doi: 10.1016/j.cgh.2023.06.011. Epub 2023 Jun 29.
BACKGROUND & AIMS: Differences in 1-year outcomes among early compared with delayed responders to vedolizumab have been shown in ulcerative colitis. However, it is unclear whether similar differences exist with ustekinumab, and what factors differentiate delayed responders from nonresponders.
This study was a post hoc analysis of patient-level data from the UNIFI clinical trial. Ustekinumab-treated patients with clinical response, defined as a reduction in total Mayo score of 30% or more and 3 or more points from baseline with a reduction in their rectal bleeding subscore of 1 or more or a rectal bleeding subscore of 1 or less, at week 8 were deemed early responders and their outcomes were compared with delayed responders (week 8 nonresponders who subsequently responded at week 16). The primary outcome assessed was 1-year clinical remission, defined as a total Mayo score of 2 or less and no subscore greater than 1.
We included 642 ustekinumab-treated patients, including 321 (50%) early responders, 115 (17.9%) delayed responders, and 205 (32.1%) nonresponders. No differences were observed for 1-year clinical remission among early vs delayed responders (132 of 321 [41.1%] vs 40 of 115 [34.8%]; P = .233), or for other outcomes assessed regardless of induction dose. Compared with early responders, delayed responders had more severe baseline Mayo endoscopic disease (88 of 115 [76.5%] vs 206 of 321 [64.2%]; P = .015) and abnormal baseline C-reactive protein level greater than 3 mg/L (83 of 115 [72.2%] vs 183 of 321 [57%]; P = .004). Compared with nonresponders, delayed responders had a significant decrease in C-reactive protein level (F-value [degrees of freedom, mean squares] [4, 844]; P < .0001) and fecal calprotectin level (F[4, 818]; P < .0001) through week 16.
Compared with early ustekinumab responders, delayed responders had a greater inflammatory burden at baseline. Early and delayed responders had similar 1-year outcomes. Biomarker decline observed in delayed responders can help differentiate them from nonresponders.
在溃疡性结肠炎中，与延迟应答者相比，早期应答者在使用维得利珠单抗治疗 1 年后的结局存在差异。然而，乌司奴单抗是否存在类似的差异，以及哪些因素可以区分延迟应答者和无应答者，目前尚不清楚。
本研究是 UNIFI 临床试验患者水平数据的事后分析。在第 8 周达到临床应答（定义为总 Mayo 评分降低 30%或以上，且基线时直肠出血评分降低 1 分或以上，或直肠出血评分降低 1 分或以下，同时总 Mayo 评分降低 3 分或以上）的乌司奴单抗治疗患者被视为早期应答者，其结局与延迟应答者（第 8 周无应答但在第 16 周应答者）进行比较。主要结局评估为 1 年临床缓解，定义为总 Mayo 评分 2 分或以下且无任何评分大于 1 分。
共纳入 642 例接受乌司奴单抗治疗的患者，其中 321 例（50%）为早期应答者，115 例（17.9%）为延迟应答者，205 例（32.1%）为无应答者。早期应答者和延迟应答者在 1 年临床缓解率方面无差异（321 例中的 132 例[41.1%] vs. 115 例中的 40 例[34.8%]；P=.233），或无论诱导剂量如何，其他结局评估均无差异。与早期应答者相比，延迟应答者的基线 Mayo 内镜疾病更严重（115 例中的 88 例[76.5%] vs. 321 例中的 206 例[64.2%]；P=.015），且基线 C 反应蛋白水平大于 3 mg/L（115 例中的 83 例[72.2%] vs. 321 例中的 183 例[57%]；P=.004）。与无应答者相比，延迟应答者的 C 反应蛋白水平（F 值[自由度，均方] [4, 844]；P<.0001）和粪便钙卫蛋白水平（F[4, 818]；P<.0001）在第 16 周显著下降。
与早期乌司奴单抗应答者相比，延迟应答者的基线炎症负担更大。早期和延迟应答者的 1 年结局相似。在延迟应答者中观察到的生物标志物下降有助于将其与无应答者区分开来。
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