Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan.
Clin Rheumatol. 2022 Feb;41(2):557-566. doi: 10.1007/s10067-021-05921-2. Epub 2021 Sep 17.
Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder with clinical heterogeneity. Although tocilizumab (TCZ), an interleukin (IL)-6 receptor inhibitor, is an effective treatment for AOSD, the evidence regarding its efficacy on systemic or articular subtypes is conflicting. Furthermore, the predictors of therapeutic response are still elusive and worthy of exploration.
This two-center retrospective study analyzed the effectiveness and safety profile of TCZ treatment in 28 patients with refractory AOSD. The 28-joint disease activity score (DAS28) and systemic activity score were assessed before and during TCZ treatment period at weeks 12, 24, 36, and 48. Plasma levels of proinflammatory cytokines at baseline were determined using ELISA method.
Among the systemic subtype patients, 10 (58.8%), 13 (76.5%), 14 (82.4%), and 15 (88.2%) patients achieved complete remission at week 12, 24, 36, and 48, respectively, in comparison to 2 (22.2%), 5 (55.6%), 6 (66.7%), and 7 (77.8%) who achieved disease remission (DAS28 < 2.6) at weeks 12, 24, 36, and 48, respectively, among articular subtype patients. The systemic activity scores and inflammatory parameters were significantly decreased after 12-week TCZ therapy, and TCZ could significantly reduce corticosteroid dose in AOSD patients. Multivariate analysis reveals that baseline IL-18 level is a significant predictor of poor therapeutic response at week 24 (odds ratio 7.86, p < 0.05).
AOSD patients refractory to high-dose corticosteroids and methotrexate may respond well to TCZ treatment with a steroid-sparing effect and an acceptable safety. A high baseline IL-18 level may be a predictor of poor therapeutic response. Key Points • Tocilizumab may be effective and well-tolerated in refractory AOSD patients regardless of disease subtypes. • High plasma levels of IL-18 may predict poor response to tocilizumab in AOSD patients.
成人斯蒂尔病（AOSD）是一种具有临床异质性的全身性炎症性疾病。尽管白细胞介素（IL）-6 受体抑制剂托珠单抗（TCZ）是治疗 AOSD 的有效药物，但关于其对全身或关节亚型疗效的证据存在矛盾。此外，治疗反应的预测因素仍不明确，值得进一步探讨。
这项回顾性的两中心研究分析了 TCZ 治疗 28 例难治性 AOSD 患者的疗效和安全性。在 TCZ 治疗期间，分别在第 12、24、36 和 48 周时评估 28 关节疾病活动评分（DAS28）和全身活动评分。采用 ELISA 法测定基线时促炎细胞因子的血浆水平。
在全身型患者中，10（58.8%）、13（76.5%）、14（82.4%）和 15（88.2%）例患者分别在第 12、24、36 和 48 周时达到完全缓解，而关节型患者中分别有 2（22.2%）、5（55.6%）、6（66.7%）和 7（77.8%）例患者在第 12、24、36 和 48 周时达到疾病缓解（DAS28＜2.6）。TCZ 治疗 12 周后，全身活动评分和炎症参数明显降低，且 TCZ 可显著减少 AOSD 患者的皮质激素剂量。多变量分析显示，基线白细胞介素-18（IL-18）水平是第 24 周时治疗反应不佳的显著预测因子（比值比 7.86，p＜0.05）。
对大剂量皮质激素和甲氨蝶呤治疗无效的 AOSD 患者可能对 TCZ 治疗有良好的反应，具有类固醇节约作用和可接受的安全性。较高的基线 IL-18 水平可能是预测 AOSD 患者治疗反应不佳的指标。
托珠单抗可能对难治性 AOSD 患者有效且耐受良好，与疾病亚型无关。
较高的血浆 IL-18 水平可能预测 AOSD 患者对托珠单抗反应不佳。
