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.

Hdl Handle:
http://hdl.handle.net/10147/207015
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; Roux-Lombard, Pascale; Veale, Douglas J; FitzGerald, Oliver; Dayer, Jean-Michel; Bresnihan, Barry
Affiliation:
Department of Rheumatology, St Vincent's University Hospital, Dublin 4, Ireland. , rooneyterence@gmail.com
Citation:
Ann Rheum Dis. 2010 Apr;69(4):706-14. Epub 2009 May 20.
Journal:
Annals of the rheumatic diseases
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207015
DOI:
10.1136/ard.2009.108324
PubMed ID:
19460761
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.
Language:
eng
MeSH:
Antirheumatic Agents/adverse effects/*therapeutic use; Arthritis, Rheumatoid/*drug therapy/immunology/radiography; Arthroscopy; Biological Markers/blood/metabolism; Disease Progression; Drug Therapy, Combination; Female; Humans; Interleukin 1 Receptor Antagonist Protein/adverse effects/therapeutic use; Male; Middle Aged; Polyethylene Glycols/adverse effects/therapeutic use; Receptors, Tumor Necrosis Factor, Type I/adverse effects/therapeutic use; Synovial Membrane/*metabolism; Treatment Outcome; Tumor Necrosis Factor-alpha/antagonists & inhibitors
ISSN:
1468-2060 (Electronic); 0003-4967 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorRooney, Terenceen_GB
dc.contributor.authorRoux-Lombard, Pascaleen_GB
dc.contributor.authorVeale, Douglas Jen_GB
dc.contributor.authorFitzGerald, Oliveren_GB
dc.contributor.authorDayer, Jean-Michelen_GB
dc.contributor.authorBresnihan, Barryen_GB
dc.date.accessioned2012-02-01T10:28:14Z-
dc.date.available2012-02-01T10:28:14Z-
dc.date.issued2012-02-01T10:28:14Z-
dc.identifier.citationAnn Rheum Dis. 2010 Apr;69(4):706-14. Epub 2009 May 20.en_GB
dc.identifier.issn1468-2060 (Electronic)en_GB
dc.identifier.issn0003-4967 (Linking)en_GB
dc.identifier.pmid19460761en_GB
dc.identifier.doi10.1136/ard.2009.108324en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207015-
dc.description.abstractOBJECTIVES: 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.en_GB
dc.language.isoengen_GB
dc.subject.meshAntirheumatic Agents/adverse effects/*therapeutic useen_GB
dc.subject.meshArthritis, Rheumatoid/*drug therapy/immunology/radiographyen_GB
dc.subject.meshArthroscopyen_GB
dc.subject.meshBiological Markers/blood/metabolismen_GB
dc.subject.meshDisease Progressionen_GB
dc.subject.meshDrug Therapy, Combinationen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshHumansen_GB
dc.subject.meshInterleukin 1 Receptor Antagonist Protein/adverse effects/therapeutic useen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshPolyethylene Glycols/adverse effects/therapeutic useen_GB
dc.subject.meshReceptors, Tumor Necrosis Factor, Type I/adverse effects/therapeutic useen_GB
dc.subject.meshSynovial Membrane/*metabolismen_GB
dc.subject.meshTreatment Outcomeen_GB
dc.subject.meshTumor Necrosis Factor-alpha/antagonists & inhibitorsen_GB
dc.titleSynovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression: analysis of a proof-of-concept randomised clinical trial of cytokine blockade.en_GB
dc.contributor.departmentDepartment of Rheumatology, St Vincent's University Hospital, Dublin 4, Ireland. , rooneyterence@gmail.comen_GB
dc.identifier.journalAnnals of the rheumatic diseasesen_GB
dc.description.provinceLeinster-

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