Chhibba Tarun, Frolkis Alexandra, Stein Levi R, Lee Sangmin, Schill Kaela, Mitevska Elena, Judge Allap K, Martin Marie-Louise, Martin Meaghan, Novak Kerri L, Lu Cathy, Ingram Richard J M, Chan Melissa M, Shukla Tushar, Seow Cynthia H, Kaplan Gilaad G, Ananthakrishnan Ashwin N, Panaccione Remo, Ma Christopher
Division of Gastroenterology, Department of Medicine, University of Toronto, 6 Queen's Park Crescent West, Third Floor, Toronto, ON M5S 3H2, Canada.
Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, 6th Floor Cal Wenzel Precision Health Building, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6, Canada.
Inflamm Bowel Dis. 2025 Aug 1;31(8):2088-2096. doi: 10.1093/ibd/izaf012.
Historically, randomized controlled trials (RCTs) have been criticized for being poorly generalizable to patients with ulcerative colitis (UC) evaluated in routine care. We aimed to evaluate the proportion of patients with UC starting an advanced therapy who would be eligible to participate in phase 3 registrational UC RCTs.
We conducted a retrospective cohort analysis of UC patients starting vedolizumab, ustekinumab, or tofacitinib at 2 IBD clinics at the University of Calgary. Patient charts, endoscopy reports, and laboratory results were reviewed, and compared against the inclusion and exclusion criteria from 5 RCTs (GEMINI-I, UNIFI, OCTAVE, ELEVATE, and LUCENT). The proportion of patients who would have been deemed eligible versus ineligible for trial participation at the time of starting a new advanced therapy was determined.
A total of 125 patients with UC were included: 78 (62.4%) would have been eligible for at least one of the considered RCTs. Trial-eligible patients were younger, less likely to be exposed to prior immunosuppressants, and had higher C-reactive protein and fecal calprotectin. The most common reason for trial ineligibility was having inadequate disease activity at baseline (Mayo endoscopy subscore <2 or absence of rectal bleeding). A significantly greater proportion of patients would have been eligible for LUCENT (45.6%) compared to GEMINI-I (24.8%), OCTAVE (35.2%), or ELEVATE (35.2%) (P < .01 for all comparisons).
Half of patients with UC starting advanced therapy in routine care may be eligible for participation in phase 3 RCTs. Disease activity is the primary reason for trial exclusion.
从历史上看，随机对照试验（RCT）一直因难以推广到在常规护理中接受评估的溃疡性结肠炎（UC）患者而受到批评。我们旨在评估开始接受高级治疗的UC患者中符合参与3期注册性UC RCT条件的比例。
我们对在卡尔加里大学的2个炎症性肠病诊所开始使用维多珠单抗、乌司奴单抗或托法替布的UC患者进行了回顾性队列分析。查阅了患者病历、内镜检查报告和实验室结果，并与5项RCT（GEMINI-I、UNIFI、OCTAVE、ELEVATE和LUCENT）的纳入和排除标准进行了比较。确定了在开始新的高级治疗时被认为符合试验条件与不符合试验条件的患者比例。
共纳入125例UC患者：78例（62.4%）至少符合一项纳入考虑的RCT条件。符合试验条件的患者更年轻，接触过先前免疫抑制剂的可能性更小，且C反应蛋白和粪便钙卫蛋白水平更高。试验不合格的最常见原因是基线时疾病活动度不足（梅奥内镜亚评分<2或无直肠出血）。与GEMINI-I（24.8%）、OCTAVE（35.2%）或ELEVATE（35.2%）相比，符合LUCENT试验条件的患者比例显著更高（45.6%）（所有比较P<0.01）。
在常规护理中开始接受高级治疗的UC患者中，有一半可能符合参与3期RCT的条件。疾病活动度是试验排除的主要原因。
