NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals Trust, Leeds, UK.
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
Expert Rev Clin Immunol. 2021 Oct;17(10):1059-1071. doi: 10.1080/1744666X.2021.1970534. Epub 2021 Aug 26.
Axial spondyloarthritis (axSpA) is an inflammatory arthritis which affects primarily the entheses of the spine and sacroiliac joints with peripheral joint synovitis and extra-articular manifestations. In 2017, the first IL-17A inhibitor (IL-17Ai) secukinumab was approved for the treatment of radiographic axSpA not responding adequately to conventional therapies, and this was followed in 2019 by a second IL-17Ai, ixekizumab. These agents represent the first alternative class of biological treatments after the TNF inhibitor which dominated the therapeutic landscape of axSpA for over a decade.
This review discusses the role of IL-17Ais in the treatment in axSpA focusing on the newest IL-17Ai ixekizumab. It provides a detailed overview of the drug pharmacodynamic, pharmacokinetics, and clinical trial data, including areas of future research needed in the post-marketing era.
Early trials of ixekizumab for axSpA have shown encouraging results and an acceptable safety profile. Future phase IV trials should focus on direct head-to-head comparisons between ixekizumab and other biologic drugs, and stratify patients according to important disease characteristics known to affect treatment response including sex, HLA-B27 status, presence of MRI bone marrow edema at baseline, disease duration and any extra-articular manifestations.
中轴型脊柱关节炎(axSpA)是一种炎症性关节炎,主要影响脊柱和骶髂关节的附着点,伴有外周关节滑膜炎和关节外表现。2017 年,首个白细胞介素-17A 抑制剂(IL-17Ai)司库奇尤单抗被批准用于治疗对常规治疗反应不足的放射学中轴型 SpA,随后在 2019 年又批准了第二个 IL-17Ai,依奇珠单抗。这些药物代表了继 TNF 抑制剂之后的首个生物治疗替代类别,TNF 抑制剂主导了 axSpA 的治疗领域超过十年。
本综述讨论了 IL-17Ai 在 axSpA 治疗中的作用,重点介绍了最新的 IL-17Ai 依奇珠单抗。它详细介绍了药物的药效学、药代动力学和临床试验数据,包括在上市后时代需要进行的未来研究领域。
依奇珠单抗治疗 axSpA 的早期试验结果令人鼓舞,安全性良好。未来的 IV 期试验应侧重于依奇珠单抗与其他生物药物的直接头对头比较,并根据已知影响治疗反应的重要疾病特征(包括性别、HLA-B27 状态、基线时 MRI 骨髓水肿的存在、疾病持续时间和任何关节外表现)对患者进行分层。