Departments of Medicine, Division of Gastroenterology, Western University, Ontario, ON, Canada.
Rheumatology Unit, Internal Medicine Service, Hospital Italiano de Buenos Aires and Instituto Universitario Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
Lancet. 2024 Oct 26;404(10463):1679-1692. doi: 10.1016/S0140-6736(24)01750-1.
Biological monoclonal antibody drugs inhibit overactive cytokine signalling that drives chronic inflammatory disease in different organ systems. In the last 10 years, interleukin (IL)-23 inhibitors have attained an important position in the treatment of psoriatic skin and joint disease as well as inflammatory bowel diseases. Addressing an upstream pathological mechanism shared between these disorders, this drug class has high efficacy rates and a durable response that extends dosing intervals up to 3 months. Pooled clinical trial data show objective disease improvement for more than 70% of patients with psoriasis and up to 50% of patients with inflammatory bowel disease. The first antibody inhibitor for IL-23A targeted a p40 subunit shared with IL-12. Subsequently, even greater improvement was established for inhibitors of the p19 protein unique to IL-23A. IL-23 p19 inhibitors elicit clinical response in both bio-naive and bio-exposed patients and show superiority to tumour necrosis factor α inhibitors in plaque psoriasis. Reported differences in efficacy between p19 inhibitors suggest that individual drug action might be modulated by antibody affinity. Although long-term safety data are accumulating, rates of serious adverse events and infections for interleukin (IL)-23 inhibitors are similar to the rates for placebo across approved indications.
生物单克隆抗体药物抑制过度活跃的细胞因子信号，从而治疗不同器官系统的慢性炎症性疾病。在过去的 10 年中，白细胞介素（IL）-23 抑制剂在治疗银屑病皮肤和关节疾病以及炎症性肠病方面占据了重要地位。针对这些疾病之间共同的上游病理机制，这类药物具有很高的疗效和持久的反应，可以将给药间隔延长至 3 个月。汇总的临床试验数据显示，超过 70%的银屑病患者和多达 50%的炎症性肠病患者的疾病有客观改善。第一个针对白细胞介素（IL）-23A 的 p40 亚单位的抗体抑制剂与 IL-12 共享。随后，针对 IL-23A 特有的 p19 蛋白的抑制剂取得了更大的改善。IL-23 p19 抑制剂在生物初治和生物暴露的患者中均能引发临床反应，并且在斑块状银屑病中优于肿瘤坏死因子α抑制剂。报道的 p19 抑制剂疗效差异表明，个体药物作用可能受到抗体亲和力的调节。尽管正在积累长期安全性数据，但在批准的适应症中，白细胞介素（IL）-23 抑制剂的严重不良事件和感染发生率与安慰剂相似。
