A. Meyer Children's Hospital, University of Florence, Firenze, Italy
J Rheumatol. 2009 Oct;36(10):2308-13. doi: 10.3899/jrheum.081156. Epub 2009 Aug 14.
To evaluate if serum concentrations of osteopontin (OPN) at baseline in patients with juvenile idiopathic arthritis (JIA) represent a potential predictor of responsiveness to methotrexate (MTX).
At diagnosis, 60 children with active JIA received MTX in addition to nonsteroidal antiinflammatory drugs. After 12 months of MTX treatment, 30 patients were defined as responders; the 30 nonresponders received anti-tumor necrosis factor-alpha therapy (etanercept) in addition to MTX; this group was then enrolled for an additional 12-month study period. No patient had received steroids within 6 weeks before entering the study. Fifty healthy children matched for sex and age acted as controls. OPN serum levels were measured at baseline, before MTX, and then at 6 and 12 months. In the nonresponder patients, OPN was evaluated again after 6 and 12 months of etanercept treatment.
At baseline, OPN values were significantly higher (p = 0.0003) in JIA patients than in controls, with no significant differences among the different JIA subtypes. At baseline, OPN levels were lower in responders than in nonresponder patients (14.16 +/- 10.1 microg/ml vs 33.2 +/- 18.1 microg/ml, respectively). After 12 months of MTX treatment, OPN levels were significantly reduced in comparison to baseline in both responder and nonresponder groups (p = 0.0017, p = 0.0048, respectively). In nonresponders, etanercept significantly reduced OPN levels at 6 and 12-month followup in comparison to baseline (p = 0.002, p = 0.008, respectively). No significant differences were found among OPN levels and disease activity.
Serum levels of OPN at baseline represent a possible marker to predict the responsiveness to MTX in patients with JIA.
评估幼年特发性关节炎(JIA)患者基线时骨桥蛋白(OPN)血清浓度是否代表对甲氨蝶呤(MTX)反应的潜在预测因子。
60 例活动性 JIA 患儿在诊断时除接受非甾体抗炎药外,还接受 MTX 治疗。MTX 治疗 12 个月后,30 例患者被定义为应答者;30 例无应答者在接受 MTX 治疗的同时接受抗肿瘤坏死因子-α治疗(依那西普);该组随后被纳入额外的 12 个月研究期。在进入研究前的 6 周内,没有患者接受过类固醇治疗。50 名性别和年龄匹配的健康儿童作为对照。在基线、MTX 治疗前以及 6 个月和 12 个月时测量 OPN 血清水平。在无应答者患者中,在接受依那西普治疗 6 个月和 12 个月后再次评估 OPN。
基线时,JIA 患者的 OPN 值明显高于对照组(p=0.0003),但不同 JIA 亚型之间无显著差异。基线时,应答者的 OPN 水平低于无应答者(分别为 14.16±10.1μg/ml 和 33.2±18.1μg/ml)。在 MTX 治疗 12 个月后,与基线相比,应答者和无应答者组的 OPN 水平均显著降低(p=0.0017,p=0.0048)。在无应答者中,与基线相比,依那西普在 6 个月和 12 个月的随访中显著降低了 OPN 水平(p=0.002,p=0.008)。在 OPN 水平和疾病活动度之间未发现显著差异。
基线时 OPN 血清水平可能是预测 JIA 患者对 MTX 反应的标志物。