李 响 1 谢 军 2
1.赣南医科大学第一临床医学院,江西 赣州 341000;2.赣南医科大学附属第一医院
摘要(Abstract):
溃疡性结肠炎(Ulcerative Colitis,UC)是一种慢性复发性的炎症性肠病,当前病因尚不完全清楚,其特征为结肠黏膜和黏膜下层的持续性炎症,严重影响了患者的生活质量,给患者生活和全球医疗系统带来了重大负担。尽管现有治疗方案包括5-氨基水杨酸制剂、免疫调节剂、类固醇及一些生物制剂在一定程度上缓解了症状,但仍存在疗效有限、副作用显著及部分患者对现有疗法耐药等问题,急需开发新的治疗药物。乌帕替尼是一种新型选择性JAK1小分子抑制剂,凭借其口服给药方式和迅速起效的特性, 在UC治疗中展现出巨大的潜力,多项国内外临床实验证明其可以改善UC患者的预后。本文将从乌帕替尼治疗UC的作用机制、临床研究进展、药物安全性等方面的研究进行综述,为未来乌帕替尼治疗UC提供新思路。
关键词(KeyWords):
溃疡性结肠炎;乌帕替尼;JAK1抑制剂;作用机制;临床研究进展
参考文献(References):
[1]C. S N ,Y. H S ,N. H .Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies(vol 390,pg 2769,2018)[J].LANCET, 2020,396(10256):E56-E56.
[2]Michael B , Joshua Q , Joseph W , et al.GLOBAL HOSPITALIZATION TRENDS FOR CROHN ’ S DISEASE AND ULCERATIVE COLITIS: SYSTEMATIC REVIEW WITH TEMPORAL ANALYSES [ J ] .Gastroenterology , 2022 , 162 (3S):S45-S46.
[3]JORDAN A A, HIGGINS P D. The role of upadacitinib in the treatment of ulcerative colitis[J/OL]. Immunotherapy,2023,15 (10): 713-727.
[4]Clare H ,Fraser R J C .JAK1 inhibition and inflammatory bowel disease[J].Rheumatology,2021,60(Supplement2):ii45-ii51.
[5]MOHAMED M E F,KLÜNDER B,OTHMAN A A. Clinical P R h h a e rum m a a c to ok id ineA tr ic th s rio ti fsU In p d a i d c a a c t i i to in ni [ b:J] Re .vi C e lw inio c fal D P at h a arRm e a lc e o vk a in n tet t io cs t, he 2020, 59(5): 531-544.
[6]Victoria A P ,Sven S ,Doerthe E , et al.Upadacitinib P in op U u lc la e tr ia o tn ivePh C a o r lm ita iscoP k a i tn ie en ti tc s s .[ a Jn] d .C E lx in p io c sau lrp e- haR rem sap c o on k s ieneR tie c lsa, tio2 n 0 s2 h 2 ip, s 62(1):101-112. [7]F M M ,Sheryl T ,Tian F , et al.Characterization of the Effect of Renal Impairment on Upadacitinib Pharmacokinetics. [J].Journal of clinical pharmacology,2019,59(6):856-862.
[8]Sheryl T ,F M M ,Tian F , et al.Characterization of the Effect of Hepatic Impairment on Upadacitinib Pharmacokinetics. [J].Journal of clinical pharmacology,2019,59(9):1188-1194.
[9]Sandborn J W ,Ghosh S ,Panes J , et al.Efficacy of Upadacitinib in a Randomized Trial of Patients With Active Ulcerative Colitis[J].Gastroenterology,2020,158(8):2139-2149.e14.
[10]Silvio D ,Séverine V ,Wen Z , et al.Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3 , multicentre , double-blind,randomised trials.[J].Lancet(London,England), 2022,399(10341):2113-2128.
[11]Séverine V ,Silvio D ,Wen Z , et al.Efficacy and safety of upadacitinib maintenance therapy for moderately to severely active ulcerative colitis in patients responding to 8 week induction therapy (U-ACHIEVE Maintenance): overall results from the randomised, placebo-controlled , double-blind , phase 3 maintenance study [ J ] .The Lancet Gastroenterology & Hepatology , 2023 , 8 (11):976-989.
[12]LOFTUS E V, COLOMBEL J F, TAKEUCHI K, et al. Upadacitinib Therapy Reduces Ulcerative Colitis Symptoms as Early as Day 1 of Induction Treatment[J]. Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association, 2023, 21(9): 2347-2358.
[13]FRIEDBERG S, CHOI D, HUNOLD T, et al. Upadaci tinib Is Effective and Safe in Both Ulcerative Colitis and Crohn’s Dise ase: Prospective Real-World Experience[J]. Clinical Gastroenterolo gy and Hepatology: The Official Clinical Practice Journal of the Ameri can Gastroenterological Association, 2023, 21(7): 1913-1923.
[14]WU H, XIE T, YU Q, et al. An Analysis of the Effectiveness and Safety of Upadacitinib in the Treatment of Inflammatory Bowel Disease: A Multicenter Real-World Study[J]. Biomedicines, 2025, 13(1): 190.
[15]MARTINEZ J,MANJALY C,MANJALY P,et al. Janus Kinase Inhibitors and Adverse Events of Acne [ J ] . JAMA Dermatology, 2023, 159(12): 1339-1345.
[16]BURMESTER G R,COHEN S B,WINTHROP K L,et al. Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis[J]. RMD Open, 2023, 9(1): e002735.