Scribano Maria Lia, Aratari Annalisa, Neri Benedetto, Bezzio Cristina, Balestrieri Paola, Baccolini Valentina, Falasco Giuliano, Camastra Caterina, Pantanella Paolo, Monterubbianesi Rita, Tullio Alessandro, Saibeni Simone, Papi Claudio, Biancone Livia, Cosintino Rocco, Faggiani Roberto
Gastroenterology Unit, Azienda Ospedaliera San Camillo Forlanini, Circonvallazione Gianicolense, 87, 00152 Rome, Italy.
IBD Unit, San Filippo Neri Hospital, Rome, Italy.
Therap Adv Gastroenterol. 2022 Feb 14;15:17562848211072412. doi: 10.1177/17562848211072412. eCollection 2022.
The effectiveness of ustekinumab in patients with refractory Crohn's disease (CD) has been investigated in several real-world studies. However, very few data concerning the real-life experience in Italy have been reported. Therefore, this study assessed the effectiveness of ustekinumab in a large cohort of Italian patients with refractory CD.
All patients who had started on ustekinumab after failure of or intolerance to antitumour necrosis factor-α (TNF-α) treatment at five tertiary centres between November 2018 and February 2020 were retrospectively enrolled. The coprimary outcome was corticosteroid-free clinical remission, defined as a Harvey-Bradshaw Index (HBI) score of ⩽4, at weeks 26 and 52. The secondary outcomes were changes in the HBI and C-reactive protein (CRP) values at weeks 8, 26, and 52 from baseline and the normalization of CRP in patients with initially abnormal values.
Totally, 140 patients who had previously received at least one anti-TNF-α agent were enrolled; 40.0% received two anti-TNF-α agents and 20.0% received vedolizumab. At baseline, 108 patients (77.1%) had HBI scores of >4; of these, 56.5% and 58.3% achieved corticosteroid-free clinical remission at weeks 26 and 52, respectively. Significant decreases in HBI and CRP values were observed at weeks 8, 26, and 52 in the entire study cohort (all < 0.0001). The CRP values were normalized in 34.9%, 37.8%, and 49.3% of the patients by weeks 8, 26, and 52, respectively. The baseline HBI score of ⩾8 was a negative predictor of corticosteroid-free clinical remission at week 52 (odds ratio: 0.21, 95% confidence interval: 0.08-0.56, = 0.002). The probability of remaining on ustekinumab after 52 weeks was 92.1%. Eleven (7.9%) patients discontinued ustekinumab (three for adverse events).
Our study findings confirm the effectiveness and safety of ustekinumab in patients with CD after failure of or intolerance to anti-TNF-α therapy.
多项真实世界研究已对优特克单抗治疗难治性克罗恩病（CD）患者的有效性进行了调查。然而，关于意大利实际情况的数据报道极少。因此，本研究评估了优特克单抗在一大群意大利难治性CD患者中的有效性。
回顾性纳入了2018年11月至2020年2月期间在五个三级中心接受抗肿瘤坏死因子-α（TNF-α）治疗失败或不耐受后开始使用优特克单抗的所有患者。共同主要结局是在第26周和第52周时无皮质类固醇临床缓解，定义为哈维-布拉德肖指数（HBI）评分≤4。次要结局是第8周、第26周和第52周时HBI和C反应蛋白（CRP）值相对于基线的变化，以及初始值异常的患者中CRP的正常化。
共纳入140例先前至少接受过一种抗TNF-α药物治疗的患者；40.0%的患者接受过两种抗TNF-α药物治疗，20.0%的患者接受过维多珠单抗治疗。基线时，108例患者（77.1%）的HBI评分>4；其中，分别有56.5%和58.3%的患者在第26周和第52周时实现了无皮质类固醇临床缓解。在整个研究队列中，第8周、第26周和第52周时观察到HBI和CRP值显著下降（均P<0.0001）。到第8周、第26周和第52周时，分别有34.9%、37.8%和49.3%的患者CRP值恢复正常。基线HBI评分≥8是第52周时无皮质类固醇临床缓解的负向预测因素（比值比：0.21，95%置信区间：0.08 - 0.56，P = 0.002）。52周后继续使用优特克单抗的概率为92.1%。11例（7.9%）患者停用了优特克单抗（3例因不良事件）。
我们的研究结果证实了优特克单抗在抗TNF-α治疗失败或不耐受的CD患者中的有效性和安全性。
