組織炎症水平高的RA患者接受TNF拮抗劑治療的效果更好

組織炎症水平高的RA患者接受TNF拮抗劑治療的效果更好
van der Pouw Kraan TC, et al. Ann Rheum Dis. 2008;67(4):563-6.

目的：不一樣患者對TNF拮抗劑的應答呈高度變異性，而相應機制尚不清楚。本研究將評價RA患者基線滑膜分子表達譜與TNF拮抗劑臨牀療效之間的關聯性。

方法：18 例活動性RA患者(DAS28 >/= 3.2)在TNF拮抗劑治療前經關節鏡活檢滑膜。治療16周時臨牀療效的定義爲DAS28評分降幅>/= 1.2，降幅<1.2則爲治療無效。利用DNA微陣列檢測滑膜標本的基因表達譜，用Pathway Analysis分析表達譜以便找到能區分治療有效與無效者的生物學進程(biological processes)。

結果：12例治療有效，6例治療無效。與治療無效者相比，多條炎症相關生物學進程在治療有效者滑膜中呈上調錶達。

結論：這些數據提示組織炎症水平高的患者更可能從TNF拮抗劑治療中獲益。
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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]