Department of Internal Medicine, Tokyo Dental College Ichikawa General Hospital, Chiba 272-8513, Japan.
J Rheumatol. 2010 Jul;37(7):1454-60. doi: 10.3899/jrheum.091285. Epub 2010 Jun 1.
To identify a biomarker for prediction of the response to infliximab (IFX) in patients with rheumatoid arthritis (RA), we focused on a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) that seems to play a key role in aggrecan degradation in cartilage.
Seventy-three randomly selected patients with active RA were treated with IFX. Peripheral blood samples were collected at baseline and ADAMTS5 messenger RNA (mRNA) was quantified using real-time polymerase chain reaction.
Baseline ADAMTS5 mRNA levels in the good responder group were significantly lower (1.84 +/- 1.56; p = 0.0408) than those in the moderate and nonresponder groups (2.54 +/- 1.70) at 38 weeks of treatment with IFX. The 28-joint count Disease Activity Score (DAS28) at 38 weeks of treatment was significantly lower in the low ADAMTS5 group (2.30 +/- 1.28; p = 0.0038) than in the high ADAMTS5 group (3.90 +/- 1.61). The percentage reduction of the DAS28 was significantly higher in the low ADAMTS5 group (52.5% +/- 28.8%; p = 0.0156) than in the high ADAMTS5 group (29.4% +/- 27.2%). Further, the Delta Health Assessment Questionnaire (DeltaHAQ) score, an estimate of the improvement in the HAQ score, at 38 weeks of treatment was significantly higher in the low ADAMTS5 group (1.18 +/- 0.60; p = 0.0102) than in the high ADAMTS5 group (0.21 +/- 0.78). The positive predictive value of a low baseline ADAMTS5 level for predicting good response and remission (DAS28 < 2.6 at 38 weeks) was 90.0% and 70.0%, respectively.
The baseline ADAMTS5 mRNA level is a candidate biomarker for prediction of the response to IFX in patients with RA.
为了寻找类风湿关节炎(RA)患者对英夫利昔单抗(IFX)应答的生物标志物,我们重点关注了在软骨中似乎对聚集蛋白聚糖降解起关键作用的解整合素金属蛋白酶 5(ADAMTS5)。
73 例活动性 RA 患者随机接受 IFX 治疗。在基线时采集外周血样,采用实时聚合酶链反应定量测定 ADAMTS5 信使 RNA(mRNA)。
IFX 治疗 38 周时,应答良好组的基线 ADAMTS5mRNA 水平显著低于应答中度和无应答组(分别为 1.84±1.56,p=0.0408)。IFX 治疗 38 周时,28 关节疾病活动度评分(DAS28)在低 ADAMTS5 组(2.30±1.28)显著低于高 ADAMTS5 组(3.90±1.61)。低 ADAMTS5 组的 DAS28 下降率(52.5%±28.8%)显著高于高 ADAMTS5 组(29.4%±27.2%)(p=0.0156)。此外,治疗 38 周时健康评估问卷(HAQ)评分的改善估计值 DeltaHAQ 评分在低 ADAMTS5 组(1.18±0.60)显著高于高 ADAMTS5 组(0.21±0.78)(p=0.0102)。基线 ADAMTS5 水平低预测 IFX 应答良好和缓解(38 周时 DAS28<2.6)的阳性预测值分别为 90.0%和 70.0%。
基线 ADAMTS5mRNA 水平是 RA 患者对 IFX 应答的候选生物标志物。