乌帕替尼治疗中度至重度活动性溃疡性结肠炎患者长期治疗目标的达成：一项3期试验数据的事后分析
Achievement of long-term treatment goals in upadacitinib-treated patients with moderately to severely active ulcerative colitis: a post hoc analysis of phase 3 trial data.
作者信息
Panés Julian, Dubinsky Marla C, Ishiguro Yoh, Shukla Nidhi, Dubcenco Elena, Remple Valencia, Sharma Dolly, Panaccione Remo
机构信息
Hospital Clinic Barcelona, IDIPABS, CIBERehd, Barcelona, Spain.
Susan and Leonard Feinstein IBD Center, Icahn School of Medicine, Mount Sinai, New York, NY, United States.
出版信息
J Crohns Colitis. 2025 Jul 3;19(7). doi: 10.1093/ecco-jcc/jjaf095.
BACKGROUND AND AIMS
Comprehensive disease control is an important yet elusive treatment goal in ulcerative colitis (UC). We evaluated the effect of upadacitinib induction and maintenance treatment on composite clinical endpoints and normalization of important health-related quality of life (HRQoL) outcomes.
METHODS
Data from the U-ACHIEVE and U-ACCOMPLISH trials were analyzed. Clinical responders to upadacitinib 45 mg 8-week induction were re-randomized 1:1:1 to upadacitinib 30 mg, 15 mg, or placebo for 52 weeks of maintenance. The percentage of patients achieving a composite clinical endpoint (clinical remission, complete symptom resolution, and Inflammatory Bowel Disease Questionnaire [IBDQ] remission) and a composite endpoint for normalization of HRQoL outcomes (Functional Assessment of Chronic Illness Therapy-Fatigue, IBDQ remission, Work Productivity and Activity Impairment Questionnaire-Ulcerative Colitis, 36-item Short Form Survey Physical Component Summary and Mental Component Survey, and EuroQol 5-Dimension 5-Level scores) was evaluated.
RESULTS
At induction week 8, more patients treated with upadacitinib 45 mg achieved the composite clinical endpoint vs placebo (6.4% vs 0.9%, P ≤ .001) and normalization of the composite HRQoL endpoint (18.9% vs 5.5%, P ≤ .001). At maintenance week 52, the composite clinical endpoint was achieved by 18.3% and 13.1% of patients treated with upadacitinib 30 mg and 15 mg, respectively, vs 4.5% with placebo (P ≤ .001). Normalization of the composite HRQoL endpoint was achieved by 24.0% and 22.3% of patients treated with upadacitinib 30 mg and 15 mg, respectively, vs 8.7% for placebo (P ≤ .001).
CONCLUSIONS
Upadacitinib may help patients with moderately to severely active UC achieve complete symptom resolution, endoscopic remission, and normalization of HRQoL.
CLINICAL REGISTRATION NUMBERS
U-ACHIEVE (NCT02819635) and U-ACCOMPLISH (NCT03653026).
背景与目的
全面疾病控制是溃疡性结肠炎（UC）治疗中的一个重要但难以实现的目标。我们评估了乌帕替尼诱导和维持治疗对复合临床终点以及重要的健康相关生活质量（HRQoL）结局正常化的影响。
方法
对U-ACHIEVE和U-ACCOMPLISH试验的数据进行分析。对接受45mg乌帕替尼8周诱导治疗的临床缓解者按1:1:1比例再次随机分组，分别接受30mg、15mg乌帕替尼或安慰剂进行52周的维持治疗。评估达到复合临床终点（临床缓解、症状完全缓解和炎症性肠病问卷[IBDQ]缓解）以及HRQoL结局正常化的复合终点（慢性病治疗功能评估-疲劳、IBDQ缓解、工作效率和活动障碍问卷-溃疡性结肠炎、36项简明健康调查身体成分汇总和精神成分调查以及欧洲五维健康量表5级评分）的患者百分比。
结果
在诱导治疗第8周，接受45mg乌帕替尼治疗的患者达到复合临床终点的比例高于安慰剂组（6.4%对0.9%，P≤0.001），达到复合HRQoL终点正常化的比例也高于安慰剂组（18.9%对5.5%，P≤0.001）。在维持治疗第52周，接受30mg和15mg乌帕替尼治疗的患者达到复合临床终点的比例分别为18.3%和13.1%，而安慰剂组为4.5%（P≤0.001）。接受30mg和15mg乌帕替尼治疗的患者达到复合HRQoL终点正常化的比例分别为24.0%和22.3%，而安慰剂组为8.7%（P≤0.001）。
结论
乌帕替尼可能有助于中度至重度活动性UC患者实现症状完全缓解、内镜缓解以及HRQoL正常化。
临床注册号
U-ACHIEVE（NCT02819635）和U-ACCOMPLISH（NCT03653026）。
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