Department of Medicine and Oncology, Semmelweis University, Budapest, Hungary.
Department of Medicine, University of Szeged, Szeged, Hungary.
Dig Liver Dis. 2022 Feb;54(2):207-213. doi: 10.1016/j.dld.2021.07.008. Epub 2021 Jul 31.
Although efficacy of ustekinumab (UST) has been demonstrated through randomized trials, data from real-life prospective cohorts are still limited. Our aim was to evaluate clinical efficacy, drug sustainability, dose intensification and results from therapeutic drug monitoring in UST treated patients with Crohn's disease (CD) using a prospective, nationwide, multicenter cohort.
Patients from 10 Inflammatory Bowel Disease centers were enrolled between 2019 January and 2020 May. Patient demographics, disease phenotype, treatment history, clinical disease activity (Crohn's Disease Activity Index(CDAI), Harvey Bradshaw Index(HBI)), biomarkers, and serum drug levels were obtained. Evaluations were performed at week8 (post-induction), w16-20, w32-36, and w52-56 follow-up visits.
A total of 142 patients were included [57.4% female; complex disease behavior (B2/B3):48%, previous anti-TNF exposition:97%]. Clinical response and remission rates after induction(w8) were 78.1% and 57.7% using CDAI, and 82.5% and 51.8% based on HBI scores. The one-year clinical remission rate was 58%/57.3%(CDAI/HBI). Composite clinical and biomarker remission (CDAI<150 and C-reactive protein<10 mg/L) rates were 35.4%; 33.3%; 38.6% and 36.6% at w8/w16-20/w32-36 and w52-56. Drug sustainability was 81.9%(standard deviation(SD): 3.4) at 1 year(1y). Probability of dose intensification was high and introduced early, 42.2%(SD:4.2) at ~w32 and 51.9%(SD:4.4%) at 1y.
Ustekinumab showed favorable drug sustainability and clinical efficacy in a patient population with severe disease phenotype and previous anti-tumor necrosis factor (anti-TNF) failure, however frequent dose intensification was required.
尽管乌司奴单抗（UST）的疗效已在随机试验中得到证实，但来自真实前瞻性队列的数据仍有限。我们的目的是使用前瞻性、全国性、多中心队列评估 UST 治疗克罗恩病（CD）患者的临床疗效、药物持续性、剂量强化和治疗药物监测结果。
2019 年 1 月至 2020 年 5 月，来自 10 个炎症性肠病中心的患者入选。获取患者人口统计学、疾病表型、治疗史、临床疾病活动度（克罗恩病活动指数（CDAI）、哈维-布拉德肖指数（HBI））、生物标志物和血清药物水平。在第 8 周（诱导后）、第 16-20 周、第 32-36 周和第 52-56 周随访时进行评估。
共纳入 142 例患者[57.4%为女性；复杂疾病行为（B2/B3）：48%，先前使用抗 TNF 药物：97%]。诱导后第 8 周（w8）时，根据 CDAI 评估的临床缓解和缓解率分别为 78.1%和 57.7%，根据 HBI 评分分别为 82.5%和 51.8%。一年临床缓解率为 58%/57.3%（CDAI/HBI）。复合临床和生物标志物缓解（CDAI<150 和 C 反应蛋白<10mg/L）率分别为 35.4%、33.3%、38.6%和 36.6%，在 w8/w16-20/w32-36 和 w52-56 时。1 年时药物持续性为 81.9%（标准差（SD）：3.4）。剂量强化的可能性较高，且早期引入，在~w32 时为 42.2%（SD：4.2），在 1 年时为 51.9%（SD：4.4%）。
在具有严重疾病表型和先前抗肿瘤坏死因子（抗 TNF）失败的患者人群中，乌司奴单抗显示出良好的药物持续性和临床疗效，但需要频繁进行剂量强化。
