Izumi Keisuke, Kaneko Yuko, Hashizume Misato, Yoshimoto Keiko, Takeuchi Tsutomu
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Department of Connective Tissue Diseases, National Tokyo Medical Center, Tokyo, Japan.
PLoS One. 2015 Dec 23;10(12):e0145468. doi: 10.1371/journal.pone.0145468. eCollection 2015.
To explore the baseline predictors of clinical effectiveness after tocilizumab or infliximab treatment in biologic-naïve rheumatoid arthritis patients.
Consecutive biologic-naïve patients with rheumatoid arthritis initiating infliximab (n = 57) or tocilizumab (n = 70) treatment were included in our prospective cohort study. Our cohort started in February 2010, and the patients observed for at least 1 year as of April 2013 were analysed. We assessed baseline variables including patients' characteristics (age, sex, disease duration, prednisolone dose, methotrexate dose, other disease-modifying antirheumatic drug use, Clinical Disease Activity Index [CDAI]) and serum biomarker levels (C-reactive protein, immunoglobulin M-rheumatoid factor, anti-cyclic citrullinated protein/peptide antibodies, interferon-γ, interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, IL-17, tumor necrosis factor-α, soluble intercellular adhesion molecule-1, bone alkaline phosphatase, osteonectin, osteopontin) to extract factors associated with clinical remission (CDAI ≤ 2.8) at 1 year using univariate analyses, and the extracted factors were entered into a multivariate logistic regression model. Similar analyses were also performed for Simplified Disease Activity Index (SDAI) remission (≤ 3.3) and Disease Activity Score with 28 joint counts, erythrocyte sedimentation rate (DAS28-ESR) remission (< 2.6).
There were no significant differences in the baseline characteristics except for methotrexate use between the groups. In the multivariate analyses, the low baseline osteopontin levels (OR 0.9145, 95% CI 0.8399-0.9857) were identified as predictors of CDAI remission in the tocilizumab group, whereas no predictors of CDAI remission were found in the infliximab group. Similar results were obtained when using SDAI and DAS28-ESR remission criteria.
Baseline low serum osteopontin levels predict clinical remission 1 year after tocilizumab treatment and not infliximab treatment in biologic-naïve patients with rheumatoid arthritis. Our prediction model provided insights into how to optimize the choice of biologics and warrants external validation in other cohorts.
探讨初治类风湿关节炎患者接受托珠单抗或英夫利昔单抗治疗后临床疗效的基线预测因素。
连续纳入初治类风湿关节炎患者,其中57例启动英夫利昔单抗治疗,70例启动托珠单抗治疗,纳入我们的前瞻性队列研究。我们的队列研究始于2010年2月,对截至2013年4月观察至少1年的患者进行分析。我们评估了基线变量,包括患者特征(年龄、性别、病程、泼尼松龙剂量、甲氨蝶呤剂量、其他改善病情抗风湿药使用情况、临床疾病活动指数[CDAI])和血清生物标志物水平(C反应蛋白、免疫球蛋白M类风湿因子、抗环瓜氨酸化蛋白/肽抗体、干扰素-γ、白细胞介素(IL)-1β、IL-2、IL-6、IL-8、IL-10、IL-17、肿瘤坏死因子-α、可溶性细胞间黏附分子-1、骨碱性磷酸酶、骨连接蛋白、骨桥蛋白),通过单因素分析提取与1年后临床缓解(CDAI≤2.8)相关的因素,并将提取的因素纳入多因素逻辑回归模型。对简化疾病活动指数(SDAI)缓解(≤3.3)和28个关节计数的疾病活动评分、红细胞沉降率(DAS28-ESR)缓解(<2.6)也进行了类似分析。
除甲氨蝶呤使用情况外,两组基线特征无显著差异。在多因素分析中,基线骨桥蛋白水平低(OR 0.9145,95%CI 0.8399-0.9857)被确定为托珠单抗组CDAI缓解的预测因素,而在英夫利昔单抗组未发现CDAI缓解的预测因素。使用SDAI和DAS28-ESR缓解标准时也得到了类似结果。
基线血清骨桥蛋白水平低可预测初治类风湿关节炎患者接受托珠单抗治疗1年后的临床缓解,而不能预测英夫利昔单抗治疗后的临床缓解。我们的预测模型为如何优化生物制剂的选择提供了见解,值得在其他队列中进行外部验证。