A prospective, randomised, placebo-controlled study to identify biomarkers associated with active treatment in psoriatic arthritis: effects of adalimumab treatment on synovial tissue.
A prospective, randomised, placebo-controlled study to identify biomarkers associated with active treatment in psoriatic arthritis: effects of adalimumab treatment on synovial tissue.
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DOI：
10.1136/ard.2008.091389
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发表时间：
2009-08
影响因子：
27.4
通讯作者：
Tak PP
中科院分区：
文献类型：
--
作者：
van Kuijk AW;Gerlag DM;Vos K;Wolbink G;de Groot M;de Rie MA;Zwinderman AH;Dijkmans BA;Tak PP
确定滑膜组织的哪种变化与有效治疗（阿达木单抗）相关的临床反应最好，以促进银屑病关节炎（PsA）治疗药物的未来研究计划。共有24例活动性PsA患者被随机分配接受阿达木单抗（n = 12）或安慰剂（n = 12）治疗4周。治疗前后4周分别行滑膜活检。免疫组织化学分析细胞浸润、细胞因子和基质金属蛋白酶（MMPs）的表达和血管的特征。切片采用数字图像分析。采用协方差分析进行统计分析。阿达木单抗治疗后，4周后28个关节的平均疾病活动评分（DAS28）比安慰剂低1.92个单位（95%置信区间（CI） 1.07至2.77）。对19例患者进行预处理和治疗后的滑膜样本配对。与安慰剂相比，阿达木单抗治疗后许多细胞类型减少。应用协方差排序分析（ANCOVA）模型校正基线失衡后，观察到治疗对cd3阳性细胞的显著影响：阿达木单抗治疗后，与安慰剂治疗相比，中位数减少了248个细胞/mm2 （p = 0.035）。此外，积极治疗后MMP13的表达显著降低：阿达木单抗治疗后的综合光密度(IOD)/mm2比安慰剂低18 190 （p = 0.033）。阿达木单抗治疗PsA与滑膜组织中T细胞浸润和MMP13表达的显著减少相关，这表明这些参数可以用作PsA小型概念验证研究中积极治疗后敏感变化的生物标志物。
To determine which of the changes in synovial tissue correlates best with clinical response associated with effective therapy (adalimumab) to facilitate the planning of future studies with therapeutic agents for psoriatic arthritis (PsA). A total of 24 patients with active PsA were randomised to receive adalimumab (n = 12) or placebo (n = 12) for 4 weeks. Synovial biopsies were obtained before and after 4 weeks of treatment. Immunohistochemical analysis was performed to characterise the cell infiltrate, expression of cytokines and matrix metalloproteinases (MMPs) and vascularity. Sections were analysed by digital image analysis. Statistical analysis was performed using covariance analysis. The mean Disease Activity Score in 28 joints (DAS28) after 4 weeks was 1.92 units lower (95% confidence interval (CI) 1.07 to 2.77) after adalimumab therapy compared with placebo. Paired pretreatment and post-treatment synovial samples were available from 19 patients. Many cell types were reduced after adalimumab treatment compared to placebo. After applying a ranked analysis of covariance (ANCOVA) model to correct for baseline imbalances, a significant effect of treatment was observed on CD3-positive cells: there was a median reduction of 248 cells/mm2 after adalimumab versus placebo treatment (p = 0.035). In addition, the expression of MMP13 was significantly reduced after active treatment: the integrated optical density (IOD)/mm2 was 18 190 lower after adalimumab treatment as compared to placebo (p = 0.033). Adalimumab therapy in PsA is associated with a marked reduction in T cell infiltration and MMP13 expression in synovial tissue, suggesting that these parameters could be used as biomarkers that are sensitive to change after active treatment in small proof of concept studies in PsA.
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4.9
作者：
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