Phase 2 Trial of Icotrokinra for Patients with Ulcerative Colitis
完整摘要 · 中文译文
背景：针对白细胞介素-23通路的单克隆抗体可有效治疗炎症性肠病。然而，这些疗法必须通过静脉注射或皮下注射给药。 方法：我们进行了一项2b期、双盲、随机试验，评估口服icotrokinra（一种阻断白细胞介素-23受体的肽）在患有中度至重度活动性溃疡性结肠炎成人中的疗效。受试者被分配接受每日一次剂量为400 mg、200 mg或100 mg的icotrokinra或安慰剂。主要终点是第12周的临床应答。次要终点包括第12周的临床缓解、症状缓解和内镜改善。 结果：共有252名参与者接受了随机分组：63人被分配到400mg组，62人分配到200mg组，64人分配到100mg组，63人分配到安慰剂组。在第12周时，icotrokinra的所有剂量组在临床应答方面均优于安慰剂组，400mg组有63%的参与者、200mg组有58%的参与者、100mg组有55%的参与者达到临床应答，而安慰剂组为27%（所有与安慰剂组的比较均P<0.001）。第12周时达到临床缓解的参与者百分比在400mg组也显著高于安慰剂组（30%对11%，P=0.006），达到症状缓解的参与者百分比（46%对19%，P<0.001）和达到内镜改善的参与者百分比（37%对14%，P=0.002）同样显著更高。第12周时临床缓解发生在200mg组的24%参与者中（与安慰剂组比较P=0.054）；根据考虑到多重比较的固定顺序检验程序，未对次要终点进行进一步正式检验。至第28周，不良事件发生率在400mg组为60%，200mg组为66%，100mg组为66%，安慰剂组为62%。严重不良事件的发生率分别为2%、5%、0%和10%。 结论：在中度至重度活动性溃疡性结肠炎受试者中，每两周一次口服艾科曲金拉（icotrokinra）在三个 tested 剂量下的第12周临床应答率均显著高于安慰剂组。（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.).
摘要 待译
New England Journal of Medicine, Volume 395, Issue 15, Page 1495-1504, October 15, 2026.