组织炎症水平高的RA患者接受TNF拮抗剂治疗的效果更好

组织炎症水平高的RA患者接受TNF拮抗剂治疗的效果更好
van der Pouw Kraan TC, et al. Ann Rheum Dis. 2008;67(4):563-6.

目的：不同患者对TNF拮抗剂的应答呈高度变异性，而相应机制尚不清楚。本研究将评价RA患者基线滑膜分子表达谱与TNF拮抗剂临床疗效之间的关联性。

方法：18 例活动性RA患者(DAS28 >/= 3.2)在TNF拮抗剂治疗前经关节镜活检滑膜。治疗16周时临床疗效的定义为DAS28评分降幅>/= 1.2，降幅<1.2则为治疗无效。利用DNA微阵列检测滑膜标本的基因表达谱，用Pathway Analysis分析表达谱以便找到能区分治疗有效与无效者的生物学进程(biological processes)。

结果：12例治疗有效，6例治疗无效。与治疗无效者相比，多条炎症相关生物学进程在治疗有效者滑膜中呈上调表达。

结论：这些数据提示组织炎症水平高的患者更可能从TNF拮抗剂治疗中获益。
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原文链接或参见以下信息。

Ann Rheum Dis. 2008 Apr;67(4):563-6. Epub 2007 Nov 27.
Responsiveness to anti-tumour necrosis factor alpha therapy is related to pre-treatment tissue inflammation levels in rheumatoid arthritis patients.
van der Pouw Kraan TC, Wijbrandts CA, van Baarsen LG, Rustenburg F, Baggen JM, Verweij CL, Tak PP.
VU University Medical Centre, Department of Molecular and Cellular Biology & Immunology, C262, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. t.vanderpouwkraan@vumc.nl

OBJECTIVE: The response of rheumatoid arthritis (RA) patients to treatment with neutralising antibodies to tumour necrosis factor alpha (TNFalpha) is highly variable. The underlying mechanism for therapy responsiveness is currently unknown. We therefore evaluated the relationship between baseline molecular profiles of synovial tissues from RA patients and the clinical response to treatment with infliximab.
METHODS: Synovial biopsies were obtained by arthroscopy from 18 RA patients with active disease (28 joint count Disease Activity Score (DAS28) > or = 3.2) before initiation of treatment with infliximab. All patients were on stable methotrexate treatment. Clinical response at 16 weeks was defined as a reduction in DAS28 of > or = 1.2, non-response as reduction in DAS28 < 1.2. Large-scale gene expression profiling using microarrays was performed on synovial tissue samples. To identify biological processes in synovial biopsies that could discriminate between responders and non-responders, we performed pathway analysis on the expression profiles.

RESULTS: A total of 12 patients responded to therapy, while 6 patients failed to fulfil the response criteria. We identified several biological processes, related to inflammation, which were up-regulated in patients who responded to therapy, compared to those who did not show clinical improvement.

CONCLUSION: These results indicate that patients with a high level of tissue inflammation are more likely to benefit from anti-TNFalpha treatment.

PMID: 18042642 [PubMed - indexed for MEDLINE]