Avci Ali Berkant, Feist Eugen, Burmester Gerd R
Department of Internal Medicine, Rheumatology, Medical Park Antalya Hospital, Antalya, Türkiye.
Department of Rheumatology, Helios Fachklinik Vogelsang-Gommern, Cooperation Partner of the Otto-von-Guericke University Magdeburg, Gommern, Germany.
BioDrugs. 2024 Jan;38(1):61-71. doi: 10.1007/s40259-023-00634-1. Epub 2023 Nov 21.
The use of different pathways in the treatment of rheumatoid arthritis has led to a significant decrease in the number of treatment-resistant patients. In this context, interleukin (IL)-6 inhibition has filled an important gap in rheumatoid arthritis treatment with its effectiveness and safety in both monotherapy and combinations. The process of IL-6 inhibition initiated with IL-6 receptor blockers has prompted questions regarding the potential impact and safety of different inhibitions of this pathway, such as the direct blockade of IL-6. Following the termination of the development of sirukumab because of mortality data in early studies, the investigation of olokizumab, which targets a different region of the IL-6 cytokine, has renewed the hope in this area and the safety concerns have been largely alleviated by the open-label extension data. In addition, the efficacy and safety of tocilizumab and sarilumab have led to a rapid investigation of biosimilars and new potent IL-6 receptor blockers. A comprehensive understanding of mechanisms of this pathway with further long-term clinical data and basic research may provide a decisive impact on selecting the appropriate mechanism as the first choice in personalized treatments.
在类风湿性关节炎治疗中使用不同途径已使治疗抵抗患者数量显著减少。在此背景下，白细胞介素（IL）-6抑制因其在单药治疗和联合治疗中的有效性和安全性，填补了类风湿性关节炎治疗中的一个重要空白。从IL-6受体阻滞剂开始的IL-6抑制过程引发了关于该途径不同抑制方式（如直接阻断IL-6）的潜在影响和安全性的问题。由于早期研究中的死亡率数据，sirukumab的研发终止后，靶向IL-6细胞因子不同区域的olokizumab的研究为该领域带来了新希望，开放标签扩展数据在很大程度上缓解了安全担忧。此外，托珠单抗和萨瑞鲁单抗的疗效和安全性促使人们迅速对生物类似药和新型强效IL-6受体阻滞剂展开研究。通过进一步的长期临床数据和基础研究全面了解该途径的机制，可能会对在个性化治疗中选择合适的机制作为首选产生决定性影响。
