Pugliese Daniela, Privitera Giuseppe, Fiorani Marcello, Parisio Laura, Calvez Valentin, Papa Alfredo, Gasbarrini Antonio, Armuzzi Alessandro
CEMAD, IBD CENTER, Unità Operativa Complessa di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Rome, Italy.
Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy.
Therap Adv Gastroenterol. 2022 Jun 13;15:17562848221102283. doi: 10.1177/17562848221102283. eCollection 2022.
As our comprehension of the pathogenic mechanisms of inflammatory bowel disease (IBD) increases, the therapeutic armamentarium for its treatment can expand, and novel target therapies join the treatment pipeline. Interleukin (IL)-12 and IL23 are two key cytokines responsible for promoting and perpetuating bowel inflammation in IBD. Ustekinumab is a monoclonal antibody directed against the shared p40 subunit of both cytokines, and it was recently approved for the treatment of ulcerative colitis (UC). In the pivotal phase III UNIFI trial, ustekinumab showed a superiority over placebo in both clinical and endoscopic outcomes; furthermore, it was characterized by a favorable safety profile, with a similar rate of adverse events as compared with placebo. Recent evidence from real-life experiences have started accumulating, generally confirming the effectiveness and safety figures emerged from the registration studies. However, most of these observational studies enrolled multirefractory patients; moreover, comparative data with other target therapies are lacking, leaving physicians without clear indications about the appropriate positioning of ustekinumab in the therapeutic pipeline for UC. This review examines the basis of targeting IL12-23 in UC therapy and summarizes the data from both clinical trials and real-life studies, to highlight the main evidence already available and the research gaps that need to be filled for the optimal usage of ustekinumab in UC.
随着我们对炎症性肠病（IBD）致病机制的理解不断加深，其治疗手段得以扩充，新型靶向治疗药物也加入了治疗行列。白细胞介素（IL）-12和IL-23是IBD中促进肠道炎症并使其持续存在的两种关键细胞因子。优特克单抗是一种针对这两种细胞因子共同的p40亚基的单克隆抗体，最近被批准用于治疗溃疡性结肠炎（UC）。在关键的III期UNIFI试验中，优特克单抗在临床和内镜检查结果方面均显示出优于安慰剂的效果；此外，其安全性良好，不良事件发生率与安慰剂相似。来自实际临床经验的最新证据开始不断积累，总体上证实了注册研究中得出的有效性和安全性数据。然而，这些观察性研究大多纳入了多重难治性患者；此外，缺乏与其他靶向治疗的对比数据，使得医生对于优特克单抗在UC治疗方案中的合理定位没有明确的参考依据。本综述探讨了在UC治疗中靶向IL-12-23的依据，并总结了临床试验和实际临床研究的数据，以突出已有的主要证据以及为在UC中优化使用优特克单抗而需要填补的研究空白。
