Division of Rheumatology, Seoul National University Hospital, Seoul, Republic of Korea ; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine, Medical Research Institute, Seoul National University, Seoul, Republic of Korea.
Division of Rheumatology, Inha University Hospital, Incheon, Republic of Korea.
J Immunol Res. 2015;2015:487230. doi: 10.1155/2015/487230. Epub 2015 Apr 2.
T helper 17-related cytokines have been implicated in rheumatoid arthritis (RA) pathogenesis. The study aimed to identify cytokines associated with the treatment response of RA patients to tocilizumab (TCZ), a humanized monoclonal antibody against the interleukin- (IL-) 6 receptor. As an independent substudy of the 24-week, randomized, double-blinded CWP-TCZ301 trial of TCZ in RA patients with an inadequate response to disease-modifying antirheumatic drugs, serum levels of cytokines including tumor necrosis factor-alpha, IL-17A, IL-21, IL-23, IL-6, and soluble IL-6 receptor were measured. Baseline IL-17A levels were significantly lower in RA patients who achieved disease activity score 28 (DAS28) remission at 12 weeks of TCZ treatment, compared to patients not in remission. Patients were stratified into IL-17A low group and IL-17A high group. Significantly more patients in the IL-17A low group achieved remission as compared to the IL-17A high group (47.6 versus 17.4%, P = 0.032). DAS28 improvement was significantly better in the IL-17A low group than in the IL-17A high group at 12 weeks (P = 0.045) and 24 weeks (P = 0.046) after adjustment. Other baseline cytokines were not associated with treatment response to TCZ. The data demonstrate that low baseline IL-17A levels are associated with better clinical response to TCZ treatment in RA patients.
辅助性 T 细胞 17 相关细胞因子与类风湿关节炎 (RA) 的发病机制有关。本研究旨在确定与 RA 患者对托珠单抗 (TCZ) 治疗反应相关的细胞因子,TCZ 是一种针对白细胞介素- (IL-) 6 受体的人源化单克隆抗体。作为 TCZ 治疗对疾病修饰抗风湿药物应答不足的 RA 患者的 24 周、随机、双盲 CWP-TCZ301 试验的独立子研究,检测了包括肿瘤坏死因子-α、IL-17A、IL-21、IL-23、IL-6 和可溶性 IL-6 受体在内的细胞因子的血清水平。与未缓解的患者相比,在 TCZ 治疗 12 周达到疾病活动评分 28 (DAS28) 缓解的 RA 患者中,基线 IL-17A 水平显著降低。患者被分为 IL-17A 低组和 IL-17A 高组。与 IL-17A 高组相比,IL-17A 低组达到缓解的患者明显更多 (47.6%对 17.4%,P = 0.032)。与 IL-17A 高组相比,IL-17A 低组在 12 周 (P = 0.045) 和 24 周 (P = 0.046) 时 DAS28 改善更显著。其他基线细胞因子与 TCZ 治疗反应无关。数据表明,基线 IL-17A 水平较低与 RA 患者对 TCZ 治疗的临床反应更好相关。