Ghannam Khetam, Zernicke Jan, Kedor Claudia, Listing Joachim, Burmester Gerd-R, Foell Dirk, Feist Eugen
Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
Epidemiology Unit, German Rheumatism Research Centre, 10117 Berlin, Germany.
J Clin Med. 2021 Sep 26;10(19):4400. doi: 10.3390/jcm10194400.
Adult-onset Still's disease (AOSD) is a systemic auto-inflammatory disease characterized by the presence of immunologically mediated inflammation and deficient resolution of inflammation. Canakinumab is an approved IL-1β inhibitor in the treatment of AOSD with a balanced efficacy and safety profile. Since inflammatory cytokines play a major role in the pathogenesis of AOSD, we investigated the effects of canakinumab on the cytokine profile of AOSD patients from a randomized controlled trial. Multiplex analysis and ELISA were used to test the concentrations of several cytokines at three time points-week 0 (baseline), week 1 and week 4-in two patient groups-placebo and canakinumab. Two-way repeated-measures analysis of variance revealed a significant temporal effect on the concentrations of MRP 8/14, S100A12, IL-6 and IL-18 with a significant decrease at week 4 in the canakinumab group exclusively. Comparing responders with non-responders to canakinumab showed a significant decrease in MRP 8/14, IL-1RA, IL-18 and IL-6 in responders at week 4, while S100A12 levels decreased significantly in responders and non-responders. In summary, canakinumab showed a striking effect on the cytokine profile in patients with AOSD, exhibiting a clear association with clinical response.
成人斯蒂尔病（AOSD）是一种全身性自身炎症性疾病，其特征为存在免疫介导的炎症且炎症消退不足。卡那单抗是一种已获批准用于治疗AOSD的IL-1β抑制剂，具有平衡的疗效和安全性。由于炎性细胞因子在AOSD的发病机制中起主要作用，我们通过一项随机对照试验研究了卡那单抗对AOSD患者细胞因子谱的影响。采用多重分析和酶联免疫吸附测定法检测了安慰剂组和卡那单抗组两组患者在三个时间点（第0周（基线）、第1周和第4周）几种细胞因子的浓度。双向重复测量方差分析显示，仅卡那单抗组在第4周时，MRP 8/14、S100A12、IL-6和IL-18的浓度有显著的时间效应且显著降低。比较卡那单抗的应答者与非应答者发现，应答者在第4周时MRP 8/14、IL-1RA、IL-18和IL-6显著降低，而应答者和非应答者的S100A12水平均显著降低。总之，卡那单抗对AOSD患者的细胞因子谱有显著影响，与临床反应有明显关联。
