Danese Silvio, Leong Rupert W, Sands Bruce E, Ma Tony, Marano Colleen, Peyrin-Biroulet Laurent
Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy.
Department of Gastroenterology, Concord Repatriation General Hospital, Concord, New South Wales, Australia.
Aliment Pharmacol Ther. 2025 Sep;62(5):483-492. doi: 10.1111/apt.70264. Epub 2025 Jul 16.
Achievement of disease clearance (simultaneous symptomatic remission and histo-endoscopic mucosal improvement [HEMI]) following induction therapy may lead to better long-term outcomes in ulcerative colitis (UC).
To evaluate disease clearance in the phase 3 UNIFI program and its association with long-term outcomes.
UNIFI comprised randomised, placebo-controlled induction and maintenance studies and a long-term extension, which evaluated intravenous ustekinumab induction (130 mg or ~6 mg/kg) and subcutaneous ustekinumab maintenance therapy (90 mg every 8 or 12 weeks) through 4 years in patients with UC.
Disease clearance was achieved by 5.9%, 15.2% and 15.1% of patients 8 weeks after placebo or ustekinumab 130 mg or ~6 mg/kg induction, respectively. Among ustekinumab induction responders randomised to ustekinumab maintenance therapy who did or did not achieve disease clearance 8 weeks after induction, 63.6% and 35.2% (nominal p < 0.001), respectively, achieved clinical remission (Mayo score ≤ 2, no individual subscore > 1) at Week 44. Among ustekinumab induction responders randomised to ustekinumab maintenance therapy who achieved disease clearance, symptomatic remission without HEMI, or neither symptomatic remission nor HEMI 8 weeks after induction, 73.4%, 53.5% (nominal p = 0.002) and 45.1% (nominal p < 0.001), respectively, achieved symptomatic remission (Mayo stool frequency subscore 0/1, rectal bleeding subscore 0) and 58.2%, 46.5% (nominal p = 0.09) and 42.7% (nominal p = 0.05), respectively, achieved Inflammatory Bowel Disease Questionnaire remission (score ≥ 170) at Week 200.
Patients who achieved disease clearance 8 weeks after ustekinumab induction were more likely to be in long-term clinical, symptomatic and quality of life remission with ustekinumab maintenance treatment than patients who did not.
NCT02407236.
诱导治疗后实现疾病清除（同时症状缓解和组织内镜黏膜改善[HEMI]）可能会使溃疡性结肠炎（UC）患者获得更好的长期预后。
评估3期UNIFI项目中的疾病清除情况及其与长期预后的关联。
UNIFI包括随机、安慰剂对照的诱导和维持研究以及一项长期扩展研究，该研究在UC患者中对静脉注射优特克单抗诱导治疗（130mg或约6mg/kg）和皮下注射优特克单抗维持治疗（每8或12周90mg）进行了4年的评估。
安慰剂、130mg优特克单抗或约6mg/kg优特克单抗诱导治疗8周后，分别有5.9%、15.2%和15.1%的患者实现了疾病清除。在诱导治疗8周后随机接受优特克单抗维持治疗且实现或未实现疾病清除的优特克单抗诱导治疗反应者中，分别有63.6%和35.2%（名义p<0.001）在第44周实现了临床缓解（梅奥评分≤2，单个子评分>1）。在诱导治疗8周后随机接受优特克单抗维持治疗且实现疾病清除、有症状缓解但无HEMI或既无症状缓解也无HEMI的优特克单抗诱导治疗反应者中，分别有73.4%、53.5%（名义p = 0.002）和45.1%（名义p<0.001）实现了症状缓解（梅奥大便频率子评分0/1，直肠出血子评分0），分别有58.2%、46.5%（名义p = 0.09）和42.7%（名义p = 0.05）在第200周实现了炎症性肠病问卷缓解（评分≥17分）。
与未实现疾病清除的患者相比，优特克单抗诱导治疗8周后实现疾病清除的患者在接受优特克单抗维持治疗时更有可能实现长期临床、症状和生活质量缓解。
NCT02407236。
