小分子制剂在炎症性肠病中的临床应用:现状与未来  

Small molecule agents in clinical management of inflammatory bowel disease:Current status and future prospects

作　　者：毛靖伟[1] Jing-Wei Mao(Department of Gastroenterology,The First Affiliated Hospital of Dalian Medical University,Dalian 116011,Liaoning Province,China)

机构地区：[1]大连医科大学附属第一医院消化内科,辽宁省大连市116011

出　　处：《世界华人消化杂志》2023年第22期913-921,共9页World Chinese Journal of Digestology

摘　　要：炎症性肠病(inflammatory bowel disease,IBD)主要包括溃疡性结肠炎和克罗恩病,属于慢性非特异性肠道炎症性疾病,其病程长、病情反复,发展至后期可增加手术、致残风险,降低患者生活质量、加重家庭及社会经济负担.目前认为遗传、免疫、肠道菌群及环境等因素均参与了疾病的发生与发展.近年来,该病在我国的发病率逐步升高,由于传统药物如5-氨基水杨酸、皮质类固醇、免疫抑制剂等疗效不足及副作用,使得一部分IBD患者的病情未能得到有效控制.在生物制剂方面,作为靶向治疗“开山者”的抗肿瘤坏死因子(tumor necrosis factor,TNF)拮抗剂应用持续时间最长、范围最为广泛,但数十年的应用数据统计显示其原发、继发失应答的人群比例较为显著.因此,新型靶向治疗药物譬如小分子制剂的不断问世,为传统治疗效果不佳及抗TNF治疗失败的人群开辟了新的道路,但小分子制剂作为一线治疗的定位亦需进一步探索研究.该文主要总结归纳近期临床试验中小分子制剂在IBD治疗中的有效性和安全性,分析其对传统生物制剂尤其是抗TNF治疗原发、继发失应答或不耐受人群的应答、缓解疗效,进行治疗决策的探索,以期探索后续理想的接续治疗药物,指导选择合适的一线靶向治疗药物.Inflammatory bowel disease(IBD),encompassing ulcerative colitis(UC)and Crohn’s disease(CD),is a chronic non-specific inflammatory disorder affecting the intestines.It is characterized by a protracted course with frequent relapses,potentially resulting in disability,heightened surgical risk,diminished patient quality of life,and increased familial and societal economic burden.Current understanding posits that genetic,immune,and environmental factors,as well as the intestinal microbiota,collectively contribute to the pathogenesis and progression of these diseases.Notably,the prevalence of IBD in China has exhibited a gradual rise in recent years.The inadequate effectiveness and adverse effects of conventional medications,including 5-aminosalicylic acid(5-ASA),corticosteroids,and immunosuppressants,have hindered the effective management of certain patients with IBD.In the realm of biological agents,anti-tumor necrosis factor(TNF)antagonists have emerged as the pioneering targeted therapy,extensively employed for an extended period.However,extensive data analysis spanning several decades reveals a notable proportion of primary and secondary loss of response to these agents.Hence,the ongoing introduction of novel targeted therapy medications,including small molecule agents,has presented a new avenue for individuals who have experienced inadequate response to conventional treatment and anti-TNF therapy.Nevertheless,additional investigation and research are required to determine the optimal role of small molecule agents as initial treatment options.This article provides a comprehensive overview of the efficacy and safety of small molecular agents in recent clinical trials for the treatment of IBD,and explores the treatment decision-making process to identify optimal subsequent treatment drugs and guide the selection of appropriate first-line targeted therapy drugs.

关 键 词：炎症性肠病 溃疡性结肠炎 克罗恩病 小分子制剂 

分 类 号：R574[医药卫生—消化系统]