Țiburcă Laura, Bembea Marius, Zaha Dana Carmen, Jurca Alexandru Daniel, Vesa Cosmin Mihai, Rațiu Ioana Adela, Jurca Claudia Maria
Faculty of Medicine and Pharmacy, University of Oradea, 1 December 10 Square, 410087 Oradea, Romania.
"Dr. Gavril Curteanu" Clinical Hospital Regional Center of Medical Genetics Bihor, 410469 Oradea, Romania.
Curr Issues Mol Biol. 2022 Apr 26;44(5):1851-1866. doi: 10.3390/cimb44050127.
IL-17 inhibitors (IL-17i) are medicines used to treat dermatological and rheumatic diseases They belong to a class of medicines called biological disease-modifying anti-rheumatic drugs (bDMARDs). This class of drugs has had a major impact on the therapy of autoimmune diseases, being much safer and more effective than treatment with small molecules. At the same time, they have highly beneficial effects on skin and joint changes, and their efficacy has been extensively monitored and demonstrated in numerous clinical trials. More and more such drugs are still being discovered today to ensure the best possible treatment of these patients, but more frequently and relatively constantly three agents are used. Two of them (Secukinumab and Ixekizumab) inhibit IL-17A directly, and the third, Brodamulab, inhibits the IL-17A receptor. Although they are extremely effective in the treatment of these diseases, sometimes their administration has been associated with paradoxical effects, i.e., there is an exacerbation of the inflammatory process. Tough, clinical trials of IL-17i have described cases of exacerbation or even onset of inflammatory bowel disease (IBD), such as Crohn's disease and ulcerative colitis, after administration of these drugs in patients previously diagnosed with psoriasis (PS), psoriatic arthritis (PsA), or ankylosing spondylitis (AS). The pathophysiological mechanism of action is not well understood at present. One explanation would be that this hyperreactive inflammatory process would be triggered by Interferon 1 derived from dendritic plasma cells. Even though there are many reports in the recent literature about the role of IL17i in the onset of IBD, conclusions of studies do not converge. Some of them show an increased incidence of IBD in patients treated with IL17i, while some others affirm their safety of them. In the near future we will surely have more data emerging from ongoing meta-analyses regarding safety of use IL17i in patients who are at risk of developing IBD. Clinical and paraclinical evaluation (inflammatory intestinal markers) are carefully advised before recommending treatment with IL-17i and after initiation of treatment, and prospective surveillance by clinical and biomarkers of patients treated with IL-17i is absolutely essential to capture the onset of IBD.
白细胞介素-17抑制剂(IL-17i)是用于治疗皮肤病和风湿性疾病的药物。它们属于一类被称为生物改善病情抗风湿药(bDMARDs)的药物。这类药物对自身免疫性疾病的治疗产生了重大影响,比小分子药物治疗更安全、更有效。同时,它们对皮肤和关节病变具有高度有益的作用,其疗效已在众多临床试验中得到广泛监测和证实。如今仍在发现越来越多这类药物,以确保对这些患者进行最佳治疗,但更常见且相对稳定使用的有三种药物。其中两种(司库奇尤单抗和依奇珠单抗)直接抑制IL-17A,第三种布罗达单抗抑制IL-17A受体。尽管它们在治疗这些疾病方面极其有效,但有时其给药会伴有矛盾效应,即炎症过程会加剧。不过,IL-17i的临床试验描述了在先前诊断为银屑病(PS)、银屑病关节炎(PsA)或强直性脊柱炎(AS)的患者中使用这些药物后,出现炎症性肠病(IBD)如克罗恩病和溃疡性结肠炎加重甚至发病的病例。目前其病理生理作用机制尚不清楚。一种解释是这种高反应性炎症过程可能由树突状浆细胞衍生的干扰素1触发。尽管最近文献中有许多关于IL17i在IBD发病中作用的报道,但研究结论并不一致。一些研究表明接受IL17i治疗的患者IBD发病率增加,而另一些则肯定其安全性。在不久的将来,我们肯定会从正在进行的荟萃分析中获得更多关于IL17i在有患IBD风险患者中使用安全性的数据。在推荐使用IL-17i治疗前以及治疗开始后,仔细进行临床和辅助临床评估(肠道炎症标志物),并且对接受IL-17i治疗的患者进行临床和生物标志物的前瞻性监测对于发现IBD的发病绝对至关重要。