Swedish Medical Center and University of Washington, Seattle.
Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts.
Arthritis Rheumatol. 2016 Sep;68(9):2163-73. doi: 10.1002/art.39700.
To evaluate the efficacy of clazakizumab, a monoclonal antibody with high affinity and specificity for the interleukin-6 (IL-6) cytokine, in psoriatic arthritis (PsA).
In this randomized, double-blind, placebo-controlled, dose-ranging study (ClinicalTrials. gov identifier: NCT01490450), patients with active PsA and an inadequate response to nonsteroidal antiinflammatory drugs were randomized (1:1:1:1) to receive subcutaneous placebo or clazakizumab 25 mg, 100 mg, or 200 mg every 4 weeks, with or without methotrexate. The primary end point was the response rate according to the American College of Rheumatology 20% criteria for improvement (ACR20) at week 16, with secondary efficacy end points at weeks 16 and 24.
A total of 165 patients were randomized. At week 16, the ACR20 response rate was significantly higher with clazakizumab 100 mg versus placebo (52.4% versus 29.3%; P = 0.039). ACR20 response rates at week 16 were 46.3% with clazakizumab 25 mg (P = 0.101 versus placebo) and 39.0% with clazakizumab 200 mg (P = 0.178 versus placebo). ACR50/ACR70 response rates were numerically higher with clazakizumab versus placebo at weeks 16 and 24. Compared with placebo, clazakizumab treatment significantly improved musculoskeletal manifestations (joint signs and symptoms, enthesitis, and dactylitis), with minimal improvements in skin disease, without clear evidence of a dose response. Clazakizumab was well tolerated.
This is the first clinical trial of an IL-6-targeted therapy in PsA. Clazakizumab may be an effective treatment option for musculoskeletal aspects of PsA, but because of the lack of a dose response in this study, further studies are required to confirm the appropriate dose. The safety profile is consistent with the pharmacology of IL-6 blockade and prior clinical experience with this antibody in rheumatoid arthritis.
评估高亲和力和特异性靶向白细胞介素-6（IL-6）细胞因子的单克隆抗体克拉扎珠单抗在银屑病关节炎（PsA）中的疗效。
在这项随机、双盲、安慰剂对照、剂量范围研究（ClinicalTrials.gov 标识符：NCT01490450）中，患有活动期 PsA 且对非甾体抗炎药反应不足的患者被随机分为（1:1:1:1）接受皮下安慰剂或克拉扎珠单抗 25 mg、100 mg 或 200 mg，每 4 周一次，联合或不联合甲氨蝶呤。主要终点是第 16 周时根据美国风湿病学会 20%改善标准（ACR20）的应答率，次要疗效终点在第 16 周和第 24 周。
共有 165 名患者被随机分组。第 16 周时，克拉扎珠单抗 100 mg 组的 ACR20 应答率显著高于安慰剂组（52.4%比 29.3%；P=0.039）。第 16 周时，克拉扎珠单抗 25 mg 组的 ACR20 应答率为 46.3%（P=0.101 与安慰剂），克拉扎珠单抗 200 mg 组为 39.0%（P=0.178 与安慰剂）。与安慰剂相比，在第 16 周和第 24 周时，克拉扎珠单抗治疗组的 ACR50/ACR70 应答率均有数值上的提高。与安慰剂相比，克拉扎珠单抗治疗可显著改善肌肉骨骼表现（关节体征和症状、肌腱端炎和指炎），皮肤疾病有轻微改善，但无明显的剂量反应证据。克拉扎珠单抗具有良好的耐受性。
这是首次在 PsA 中进行靶向白细胞介素-6 治疗的临床试验。克拉扎珠单抗可能是治疗 PsA 肌肉骨骼方面的有效治疗选择，但由于本研究中未观察到剂量反应，因此需要进一步研究来确认合适的剂量。安全性概况与 IL-6 阻断的药理学和该抗体在类风湿关节炎中的先前临床经验一致。
