Prevalence, characteristics, management, and outcomes of difficult-to-treat inflammatory bowel disease

Tommaso Lorenzo Parigi, Luca Massimino, Alfredo Carini, Roberto Gabbiadini, Peter Bertoli, Mariangela Allocca, Cristina Bezzio, Arianna Dal Buono, Ferdinando D’Amico, Federica Furfaro, Laura Loy, Alessandra Zilli, Federica Ungaro, Vipul Jairath, Laurent Peyrin-Biroulet, Alessandro Armuzzi, Silvio Danese
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Abstract

Background and Aim Criteria for "difficult-to-treat" Inflammatory Bowel Disease (IBD) (DTT-IBD) have recently been proposed to standardize terminology. We aimed to evaluate the prevalence, characteristics, management, and outcomes of DTT-IBD. Methods We conducted a retrospective study in two tertiary centers in Italy. Results Among 1736 IBD patients treated with biologics/advanced small molecules, 430 (24.8%) met at least one DTT-IBD criterion, of which 331 (77%) failed at least 2 mechanisms of action. In ulcerative colitis (UC), left-sided and extended colitis were risk factors for DTT compared to proctitis (OR 6.55, 1.93-40.98, p=0.011; and OR 10.12, 3.01-63.14, p=0.002, respectively). In Crohn’s disease (CD), multiple localizations (L3+L4) (OR 3.04, 1.09-8.34, p=0.03), stricturing (OR 2.24, 1.52-3.34, p<0.001) and penetrating (OR 2.33, 1.55-3.53, p<0.001) behaviors, and perianal disease (OR 2.49, 1.75-3.53, p<0.001) were the main risk factors for DTT. Delay in advanced treatment initiation was positively associated with DTT-CD (OR 1.74, 1.27–2.41 p=0.001) but protective in UC (OR 0.65, 0.45-0.93 p=0.019). The rates of symptomatic, biochemical, and endoscopic remission were lower in DTT-IBD compared to non-DTT-IBD. The difference was most evident for endoscopic remission (25% vs 62%). Drug persistency in each following line of treatment progressively decreased in CD and UC. All advanced drugs used in DTT-IBD had similar persistence. Conclusions DTT-IBD was prevalent in approximately one-quarter of patients with IBD in a tertiary care setting. Certain IBD phenotypes and the delay in initiating treatment in CD were risk factors for DTT. Drug persistency decreased progressively with every subsequent line of therapy.
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难以治疗的炎症性肠病的发病率、特征、管理和结果
背景和目的 最近提出了 "难治性 "炎症性肠病(IBD)(DTT-IBD)的标准,以统一术语。我们旨在评估 DTT-IBD 的患病率、特征、管理和预后。方法 我们在意大利的两个三级医疗中心进行了一项回顾性研究。结果 在接受生物制剂/先进小分子药物治疗的 1736 名 IBD 患者中,430 人(24.8%)至少符合一项 DTT-IBD 标准,其中 331 人(77%)至少有两种作用机制失败。在溃疡性结肠炎(UC)中,与直肠炎相比,左侧结肠炎和扩展性结肠炎是导致 DTT 的危险因素(OR 分别为 6.55,1.93-40.98,p=0.011;OR 分别为 10.12,3.01-63.14,p=0.002)。在克罗恩病(CD)中,多发定位(L3+L4)(OR 3.04,1.09-8.34,p=0.03)、严密性(OR 2.24,1.52-3.34,p<0.001)和穿透性(OR 2.33,1.55-3.53,p<0.001)行为和肛周疾病(OR 2.49,1.75-3.53,p<0.001)是 DTT 的主要危险因素。延迟开始晚期治疗与 DTT-CD 呈正相关(OR 1.74,1.27-2.41 p=0.001),但对 UC 具有保护作用(OR 0.65,0.45-0.93 p=0.019)。与非 DTT-IBD 相比,DTT-IBD 的症状缓解率、生化缓解率和内镜缓解率都较低。差异最明显的是内镜缓解率(25% 对 62%)。在 CD 和 UC 中,每种后续治疗药物的持续用药时间逐渐缩短。所有用于 DTT-IBD 的晚期药物都具有相似的持续性。结论 在三级医疗机构中,约四分之一的 IBD 患者普遍患有 DTT-IBD。某些 IBD 表型和 CD 延误开始治疗是 DTT 的风险因素。药物持续性随着每种后续疗法的进行而逐渐降低。
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