Centocor Research and Development, Inc, 200 Great Valley Parkway, Malvern, PA 19355, USA.
Arthritis Res Ther. 2010;12(6):R211. doi: 10.1186/ar3188. Epub 2010 Nov 17.
The goal of this study was to identify serum markers that are modulated by treatment with golimumab with or without methotrexate (MTX) and are associated with clinical response.
Sera were collected at weeks 0 and 4 from a total of 336 patients (training dataset, n = 100; test dataset, n = 236) from the GO-FORWARD study of patients with active rheumatoid arthritis despite MTX. Patients were randomly assigned to receive placebo plus MTX; golimumab, 100 mg plus placebo; golimumab, 50 mg plus MTX; or golimumab, 100 mg plus MTX. Subcutaneous injections were administered every 4 weeks. Samples were tested for select inflammatory, bone, and cartilage markers and for protein profiling using multianalyte profiles.
Treatment with golimumab with or without MTX resulted in significant decreases in a variety of serum proteins at week 4 as compared with placebo plus MTX. The American College of Rheumatology (ACR) 20, ACR 50, and Disease Activity Score (DAS) 28 responders showed a distinct biomarker profile compared with nonresponding patients.
ACR 20 and ACR 50 responders among the golimumab/golimumab + MTX-treated patients had a distinct change from baseline to week 4 in serum protein profile as compared with nonresponders. Some of these changed markers were also associated with multiple clinical response measures and improvement in outcome measures in golimumab/golimumab + MTX-treated patients. Although the positive and negative predictive values of the panel of markers were modest, they were stronger than C-reactive protein alone in predicting clinical response to golimumab.
http://ClinicalTrials.gov identification number: NCT00264550.
本研究的目的是鉴定出经戈利木单抗治疗（联合或不联合甲氨蝶呤[MTX]）后发生变化且与临床应答相关的血清标志物。
GO-FORWARD 研究共纳入 336 例活动性类风湿关节炎患者（训练数据集，n=100；测试数据集，n=236），这些患者尽管接受 MTX 治疗但病情仍未得到控制。患者被随机分配接受安慰剂+MTX、戈利木单抗 100 mg+安慰剂、戈利木单抗 50 mg+MTX 或戈利木单抗 100 mg+MTX 治疗。每 4 周皮下注射一次。采集血清样本，使用多分析物谱检测特定的炎症、骨骼和软骨标志物及蛋白质谱。
与安慰剂+MTX 组相比，戈利木单抗联合或不联合 MTX 治疗可显著降低第 4 周时多种血清蛋白水平。与无应答者相比，美国风湿病学会（ACR）20、ACR 50 和疾病活动评分（DAS）28 应答者在戈利木单抗/戈利木单抗+MTX 治疗患者中表现出明显不同的生物标志物特征。
与无应答者相比，戈利木单抗/戈利木单抗+MTX 治疗患者中 ACR 20 和 ACR 50 应答者从基线到第 4 周时的血清蛋白谱发生了明显改变。在戈利木单抗/戈利木单抗+MTX 治疗患者中，这些变化的标志物中的一些与多种临床应答指标以及结局改善指标相关。虽然该标志物组合的阳性和阴性预测值适中，但与 C 反应蛋白相比，其预测戈利木单抗临床应答的能力更强。
http://ClinicalTrials.gov 注册号：NCT00264550。
