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Title

Synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression: analysis of a proof-of-concept randomised clinical trial of cytokine blockade

Authors
Rooney, Terence
Veale, Douglas J.
FitzGerald, Oliver
Published in Annals of the Rheumatic Diseases. 2010, vol. 69, no. 4, p. 706-714
Abstract OBJECTIVES: To evaluate synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression during biological therapy for rheumatoid arthritis (RA). METHODS: Patients with active RA entered a randomised study of anakinra 100 mg/day, administered as monotherapy or in combination with pegsunercept 800 microg/kg twice a week. Arthroscopic synovial tissue biopsies were obtained at baseline and two further time points. Following immunohistochemical staining, selected mediators of RA pathophysiology were quantified using digital image analysis. Selected mediators were also measured in the serum. RESULTS: Twenty-two patients were randomly assigned: 11 received monotherapy and 11 combination therapy. American College of Rheumatology 20, 50 and 70 response rates were 64%, 64% and 46% with combination therapy and 36%, 9% and 0% with monotherapy, respectively. In synovial tissue, T-cell infiltration, vascularity and transforming growth factor beta (TGFbeta) expression demonstrated significant utility as biomarkers of disease activity and therapeutic response. In serum, interleukin 6 (IL-6), matrix metalloproteinase (MMP) 1, MMP-3 and tissue inhibitor of metalloproteinase 1 (TIMP-1) were most useful in this regard. An early decrease in serum levels of TIMP-1 was predictive of the later therapeutic outcome. Pretreatment tissue levels of T-cell infiltration and the growth factors vascular endothelial growth factor/TGFbeta, and serum levels of IL-6, IL-8, MMP-1, TIMP-1, soluble tumour necrosis factor receptor types I and II and IL-18 correlated with radiographic progression. CONCLUSIONS: Synovial tissue analysis identified biomarkers of disease activity, therapeutic response and radiographic progression. Biomarker expression in tissue was independent of the levels measured in the serum.
Keywords Antirheumatic Agents/adverse effects/*therapeutic useArthritis, Rheumatoid/*drug therapy/immunology/radiographyArthroscopyBiological Markers/blood/metabolismDisease ProgressionDrug Therapy, CombinationFemaleHumansInterleukin 1 Receptor Antagonist Protein/adverse effects/therapeutic useMaleMiddle AgedPolyethylene Glycols/adverse effects/therapeutic useReceptors, Tumor Necrosis Factor, Type I/adverse effects/therapeutic useSynovial Membrane/*metabolismTreatment OutcomeTumor Necrosis Factor-alpha/antagonists & inhibitors
Identifiers
PMID: 19460761
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Other version: http://ard.bmj.com/content/69/4/706.full.pdf
Structures
Research group Etude de l'activation des monocytes/macrophages et des polynucléaires neutrophiles (779)
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ROONEY, Terence et al. Synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression: analysis of a proof-of-concept randomised clinical trial of cytokine blockade. In: Annals of the Rheumatic Diseases, 2010, vol. 69, n° 4, p. 706-714. https://archive-ouverte.unige.ch/unige:21265

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Deposited on : 2012-05-23

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