乌帕替尼（Icotrokinra）治疗溃疡性结肠炎的2期试验。
完整摘要 · 中文译文
背景：靶向白细胞介素-23通路的单克隆抗体在治疗炎症性肠病方面有效。然而，这些疗法必须通过静脉注射或皮下注射给药。 方法：我们开展了一项口服icotrokinra的2b期、双盲、随机试验，icotrokinra是一种阻断白细胞介素-23受体的肽，受试者为中度至重度活动性溃疡性结肠炎成人患者。参与者被分配接受icotrokinra每日一次400 mg、200 mg或100 mg剂量或安慰剂。主要终点为第12周时的临床应答。次要终点包括第12周时的临床缓解、症状缓解和内镜下改善。 结果：共有252名参与者接受了随机化：63名被分配至400 mg组，62名至200 mg组，64名至100 mg组，63名至安慰剂组。在第12周临床应答方面，所有icotrokinra剂量均优于安慰剂，400 mg组63%的参与者、200 mg组58%和100 mg组55%的参与者出现临床应答，而安慰剂组为27%（与安慰剂的所有比较P<0.001）。第12周时达到临床缓解的参与者百分比在400 mg组也显著高于安慰剂组（30% vs. 11%，P = 0.006），达到症状缓解的参与者百分比（46% vs. 19%，P<0.001）以及达到内镜下改善的参与者百分比（37% vs. 14%，P = 0.002）亦然。第12周时临床缓解发生于20 0-mg组（与安慰剂比较的P = 0.054）；根据固定顺序检验程序以考虑多重比较，未对次要终点进行进一步正式检验。截至第28周，出现不良事件的参与者百分比在400-mg组为60%，200-mg组为66%，100-mg组为66%，安慰剂组为62%。就严重不良事件而言，各组的百分比分别为2%、5%、0%和10%。 结论：在中度至重度活动性溃疡性结肠炎参与者中，每日一次口服伊科曲金（icotrokinra）在三个测试剂量下的第12周临床应答率均显著高于安慰剂。（由强生公司资助；ANTHEM-UC临床试验注册号，NCT06049017。）
完整摘要 · 英文原文
BACKGROUND: Monoclonal antibodies targeting the interleukin-23 pathway are effective in treating inflammatory bowel disease. However, these therapies must be administered intravenously or by subcutaneous injection. METHODS: We conducted a phase 2b, double-blind, randomized trial of oral icotrokinra, a peptide that blocks the interleukin-23 receptor, in adults with moderately to severely active ulcerative colitis. Participants were assigned to receive icotrokinra at a once-daily dose of 400 mg, 200 mg, or 100 mg or placebo. The primary end point was clinical response at week 12. Secondary end points included clinical remission, remission of symptoms, and endoscopic improvement at week 12. RESULTS: A total of 252 participants underwent randomization: 63 were assigned to the 400-mg group, 62 to the 200-mg group, 64 to the 100-mg group, and 63 to the placebo group. All the doses of icotrokinra were superior to placebo with respect to a clinical response at week 12, which occurred in 63% of the participants in the 400-mg group, 58% in the 200-mg group, and 55% in the 100-mg group, as compared with 27% in the placebo group (P<0.001 for all comparisons with placebo). The percentage of participants with clinical remission at week 12 was also significantly higher in the 400-mg group than in the placebo group (30% vs. 11%, P = 0.006), as were the percentage of participants with symptomatic remission (46% vs. 19%, P<0.001) and the percentage of participants with endoscopic improvement (37% vs. 14%, P = 0.002). Clinical remission at week 12 occurred in 24% of the participants in the 200-mg group (P = 0.054 for the comparison with placebo); in accordance with the fixed-sequence testing procedure to account for multiple comparisons, no further formal testing of secondary end points was conducted. Through week 28, the percentage of participants with adverse events was 60% in the 400-mg group, 66% in the 200-mg group, 66% in the 100-mg group, and 62% in the placebo group. For serious adverse events, the percentages were 2%, 5%, 0%, and 10%, respectively. CONCLUSIONS: Among participants with moderately to severely active ulcerative colitis, a clinical response at week 12 was significantly more common with once-daily oral icotrokinra at each of three tested doses than with placebo. (Funded by Johnson & Johnson; ANTHEM-UC ClinicalTrials.gov number, NCT06049017.).