Sabino João, Verstockt Bram, Vermeire Séverine, Ferrante Marc
Universitaire Ziekenhuizen Leuven, Belgium.
Universtaire Ziekenhuizen Leuven, Herestraat 49, Leuven B3000, Belgium.
Therap Adv Gastroenterol. 2019 May 26;12:1756284819853208. doi: 10.1177/1756284819853208. eCollection 2019.
Inflammatory bowel disease (IBD) is a spectrum of immune-mediated inflammatory disorders with a complex multifactorial pathogenesis, where different pathways may predominate in different individuals. This complexity will most likely require a panoply of drugs targeting different pathways if one wants to treat to steroid-free sustained remission and mucosal healing. Presently, the mainstay of medical management of IBD is based on 5-aminosalicylates, corticosteroids, thiopurines, methotrexate, antitumor necrosis factor, anti-alpha4 beta7 (α4β7) integrin and anti-interleukin (IL)-12/IL-23 therapies. The discovery of new pathways involved in the pathogenesis of IBD resulted in new drugs targeting Janus kinase/signal transducers and activators of transcription, IL-6, spingosine-1-phosphate, and phosphodiesterase 4, among others. These new therapies might result in more advantageous safety profiles. Several of these new drugs have already been successfully tested in other inflammatory disorders, such as psoriasis or rheumatoid arthritis. In this review, evidence from phase II and phase III randomized controlled clinical trials in patients with IBD involving new biologicals and small molecules are summarized.
炎症性肠病(IBD)是一系列免疫介导的炎症性疾病,其发病机制复杂且多因素,不同个体中可能有不同的途径占主导。如果想要实现无类固醇的持续缓解和黏膜愈合,这种复杂性很可能需要一系列针对不同途径的药物。目前,IBD药物治疗的主要手段基于5-氨基水杨酸类、皮质类固醇、硫唑嘌呤、甲氨蝶呤、抗肿瘤坏死因子、抗α4β7整合素和抗白细胞介素(IL)-12/IL-23疗法。IBD发病机制中涉及的新途径的发现催生了针对Janus激酶/信号转导和转录激活因子、IL-6、鞘氨醇-1-磷酸和磷酸二酯酶4等的新药。这些新疗法可能会带来更有利的安全性。其中几种新药已在其他炎症性疾病,如银屑病或类风湿关节炎中成功进行了测试。在本综述中,总结了IBD患者中涉及新生物制剂和小分子的II期和III期随机对照临床试验的证据。