Anti-Integrins, Anti-Interleukin 12/23p40, and JAK Inhibitors for the Inflammatory Bowel Disease Treatment

K. M. Steigleder, F. L. P. Neto, Cristiane Kibune Nagasako, R. Leal
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Abstract

Inflammatory bowel diseases (IBD) present a broad inflammatory cascade that is sometimes difficult to control. Patients with ulcerative colitis (UC) and Crohn’s disease (CD) are exposed to intense and harmful effects that compromise their quality of life. There is a constant need for new classes of drugs that act on different fronts of inflammation control. Initially, biologics revolutionized inflammatory bowel disease treatment. Anti-tumor necrosis factor (anti-TNF) agents and infliximab, followed by adalimumab and certolizumab pegol, have been proven to induce clinical and endoscopic remission. However, some patients are primary nonresponders, and a significant proportion of initial responders lose response throughout the treatment. The emergence of new therapies, such as anti-integrins, anti-interleukins, and inhibitors of Janus kinase (JAK), can become an alternative option for patients with previous therapeutic failures, besides offering greater safety than other biological therapies up to now. Among anti-integrins, vedolizumab is the drug with proven efficacy in both induction and maintenance of remission and has local and selective action in the intestine. Ustekinumab repre-sents the group of anti-interleukins, acting to control interleukin-12 (IL12) and interleukin-23 (IL23). JAK inhibitors (tofacitinib) act on intracellular inflammatory mediators and have the advantage of being orally administered. of vedolizumab in patients with previous anti-TNF treatment. The study showed an advantage of
抗整合素、抗白细胞介素12/23p40和JAK抑制剂治疗炎症性肠病
炎症性肠病(IBD)表现出广泛的炎症级联反应,有时难以控制。溃疡性结肠炎(UC)和克罗恩病(CD)患者暴露于严重和有害的影响,损害了他们的生活质量。人们不断需要新型药物来控制炎症的不同方面。最初,生物制剂彻底改变了炎症性肠病的治疗。抗肿瘤坏死因子(anti-TNF)药物和英夫利昔单抗,其次是阿达木单抗和certolizumab pegol,已被证明可诱导临床和内镜下缓解。然而,一些患者是原发性无应答者,并且相当大比例的初始应答者在整个治疗过程中失去应答。新疗法的出现,如抗整合素、抗白细胞介素和Janus激酶抑制剂(JAK),可以成为以前治疗失败的患者的另一种选择,而且比目前其他生物疗法具有更高的安全性。在抗整合素中,vedolizumab是一种被证实在诱导和维持缓解方面都有效的药物,并且在肠道中具有局部和选择性作用。Ustekinumab代表抗白介素组,作用于控制白细胞介素-12 (il -12)和白细胞介素-23 (il -23)。JAK抑制剂(托法替尼)作用于细胞内炎症介质,具有口服给药的优点。vedolizumab在既往抗tnf治疗患者中的应用。研究显示了……的优势
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