College of Pharmacy, Chung-Ang University, 84 Heukseokro, Dongjakgu, Seoul, 06974, Korea.
Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, 06974, Korea.
Arch Pharm Res. 2021 Mar;44(3):293-309. doi: 10.1007/s12272-021-01318-6. Epub 2021 Mar 24.
Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory disease characterized by intestinal inflammation and epithelial injury. For the treatment of IBD, 5-aminosalicylic acids, corticosteroids, immunomodulators, and biologic agents targeting tumor necrosis factor (TNF)-α, α4β7-integrin, and interleukin (IL)-12/23 have been widely used. Especially, anti-TNF-α antibodies are the first biologic agents that presently remain at the forefront. However, 10-30% of patients resist biologic agents, including anti-TNF-α agents (primary non-responder; PNR), and 20-50% of primary responders develop treatment resistance within one year (secondary loss of response; SLR). Nonetheless, the etiologies of PNR and SLR are not clearly understood, and predictors of response to biologic agents are also not defined yet. Numerous studies are being performed to discover prediction markers of the response to biologic agents, and this review will introduce currently available therapeutic options for IBD, biologics under investigation, and recent studies exploring various predictive factors related to PNR and SLR.
炎症性肠病(IBD),包括溃疡性结肠炎(UC)和克罗恩病(CD),是一种以肠道炎症和上皮损伤为特征的慢性炎症性疾病。对于 IBD 的治疗,5-氨基水杨酸、皮质类固醇、免疫调节剂和针对肿瘤坏死因子(TNF)-α、α4β7-整合素和白细胞介素(IL)-12/23 的生物制剂已被广泛应用。特别是,抗 TNF-α 抗体是目前处于前沿的第一种生物制剂。然而,10-30%的患者对生物制剂(包括抗 TNF-α 制剂)有耐药性(原发性无应答;PNR),并且 20-50%的原发性应答者在一年内会出现治疗抵抗(继发性应答丧失;SLR)。尽管如此,PNR 和 SLR 的病因尚不清楚,生物制剂的应答预测因子也尚未确定。目前正在进行大量研究以发现生物制剂应答的预测标志物,本综述将介绍目前 IBD 的治疗选择、正在研究的生物制剂以及最近探索与 PNR 和 SLR 相关的各种预测因素的研究。