University Hospitals of Geneva, Geneva, Switzerland.
Charité - University Medicine Berlin, Berlin, Germany.
Arthritis Res Ther. 2020 Apr 7;22(1):70. doi: 10.1186/s13075-020-02163-6.
Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a key role in the pathogenesis of rheumatoid arthritis. Sarilumab is a human monoclonal antibody that binds membrane-bound and soluble IL-6 receptor-α to inhibit IL-6 signalling. The aim of this study was to compare the effects of sarilumab and adalimumab (a tumour necrosis factor alpha inhibitor) monotherapy on levels of circulating biomarkers associated with the acute-phase response, bone remodelling, atherothrombosis, anaemia of chronic disease and markers purported to reflect synovial lymphoid and myeloid cell infiltrates, as well as the potential of these biomarkers to differentially predict clinical and patient-reported outcomes with sarilumab vs. adalimumab.
In this post hoc analysis, serum samples were analysed at baseline and prespecified post-treatment timepoints up to week 24 in adults with moderate-to-severe active rheumatoid arthritis intolerant of or inadequate responders to methotrexate from the MONARCH trial (NCT02332590).
Greater reductions in C-reactive protein (CRP; - 94.0% vs. -24.0%), serum amyloid A (SAA; - 83.2% vs. -17.4%), total receptor activator of nuclear factor-κB ligand (RANKL; - 18.3% vs. 10.5%) and lipoprotein (a) (- 41.0% vs. -2.8%) were observed at week 24 with sarilumab vs. adalimumab, respectively (adjusted p < 0.0001). Greater increases in procollagen type 1 N-terminal propeptide (P1NP) were observed with sarilumab vs. adalimumab at week 24 (22.8% vs. 6.2%, p = 0.027). Patients with high baseline SAA, CRP and matrix metalloproteinase-3 (MMP-3) were more likely to achieve clinical efficacy, including American College of Rheumatology 20% improvement criteria and Disease Activity Score (28 joints)-CRP < 3.2, and report improvements in patient-reported outcomes, including Health Assessment Questionnaire-Disability Index and pain visual analogue scale, with sarilumab than adalimumab.
Sarilumab was associated with greater positive effects on bone remodelling and decreases in biomarkers of the acute-phase response, synovial inflammation and cardiovascular risk vs. adalimumab. High baseline concentrations of SAA, CRP and MMP-3 are predictive of clinical and patient-reported outcome responses to sarilumab treatment and prospective validation is warranted to confirm these results.
ClinicalTrials.gov, NCT02332590. Registered on 5 January 2015.
白细胞介素-6（IL-6）是一种多效细胞因子，在类风湿关节炎发病机制中起关键作用。沙利鲁单抗是一种人源化单克隆抗体，可结合膜结合和可溶性白细胞介素-6 受体-α，从而抑制白细胞介素-6 信号传导。本研究旨在比较沙利鲁单抗和阿达木单抗（一种肿瘤坏死因子-α抑制剂）单药治疗对与急性期反应、骨重塑、动脉粥样血栓形成、慢性疾病贫血以及据称反映滑膜淋巴样和髓样细胞浸润的标志物相关的循环生物标志物水平的影响，以及这些生物标志物对预测沙利鲁单抗与阿达木单抗治疗的临床和患者报告结果的潜在差异的能力。
在这项事后分析中，来自 MONARCH 试验（NCT02332590）的对甲氨蝶呤不耐受或应答不足的中度至重度活动期类风湿关节炎成年患者，在基线和预设的治疗后时间点（至第 24 周）分析血清样本。
与阿达木单抗相比，沙利鲁单抗在第 24 周时观察到 C 反应蛋白（CRP；-94.0% vs. -24.0%）、血清淀粉样蛋白 A（SAA；-83.2% vs. -17.4%）、总核因子-κB 受体激活剂配体（RANKL；-18.3% vs. 10.5%）和脂蛋白（a）（-41.0% vs. -2.8%）的降低更为明显（调整后的 p < 0.0001）。与阿达木单抗相比，沙利鲁单抗在第 24 周时观察到前胶原 1 N 端前肽（P1NP）的增加更为明显（22.8% vs. 6.2%，p = 0.027）。基线 SAA、CRP 和基质金属蛋白酶-3（MMP-3）较高的患者更有可能实现临床疗效，包括美国风湿病学会 20%的改善标准和疾病活动评分（28 个关节）-CRP <3.2，以及报告患者报告的结局（包括健康评估问卷残疾指数和疼痛视觉模拟量表）的改善，沙利鲁单抗优于阿达木单抗。
与阿达木单抗相比，沙利鲁单抗对骨重塑具有更大的积极影响，并降低急性期反应、滑膜炎症和心血管风险的生物标志物。较高的基线 SAA、CRP 和 MMP-3 浓度可预测沙利鲁单抗治疗的临床和患者报告结局反应，需要前瞻性验证来确认这些结果。
ClinicalTrials.gov，NCT02332590。于 2015 年 1 月 5 日注册。
