Synovial tissue sublining CD68 expression is a biomarker of therapeutic response in rheumatoid arthritis clinical trials: consistency across centers.

Hdl Handle:
http://hdl.handle.net/10147/207489
Title:
Synovial tissue sublining CD68 expression is a biomarker of therapeutic response in rheumatoid arthritis clinical trials: consistency across centers.
Authors:
Bresnihan, Barry; Pontifex, Eliza; Thurlings, Rogier M; Vinkenoog, Marjolein; El-Gabalawy, Hani; Fearon, Ursula; Fitzgerald, Oliver; Gerlag, Danielle M; Rooney, Terence; van de Sande, Marleen G; Veale, Douglas; Vos, Koen; Tak, Paul-Peter
Affiliation:
St. Vincent's University Hospital, Dublin, Ireland. barry.bresnihan@gmail.com
Citation:
J Rheumatol. 2009 Aug;36(8):1800-2.
Journal:
The Journal of rheumatology
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207489
DOI:
10.3899/jrheum.090348
PubMed ID:
19671815
Abstract:
OBJECTIVE: To determine whether the correlation between the mean change in disease activity and the mean change in synovial sublining (sl) CD68 expression could be demonstrated across different academic centers. METHODS: Synovial biopsies obtained at arthroscopy from patients with rheumatoid arthritis before and 160 days after rituximab therapy were selected and coded. Paired sections were processed independently at Amsterdam Medical Center (AMC) and at St. Vincent's University Hospital (SVUH), Dublin. Digital image analysis (DIA) was employed at both centers to quantify sublining CD68 expression. RESULTS: After analysis of CD68sl expression at centers in 2 different countries, high levels of intracenter and intercenter agreement were observed. For the pooled sections stained at AMC, the correlation between 2 investigators was R = 0.942, p = 0.000, and for sections stained at SVUH, R = 0.899, p = 0.001. Similarly, the intracenter correlations for DeltaCD68sl expression after treatment were R = 0.998, p = 0.000, for sections stained at AMC and R = 0.880, p = 0.000, for sections stained at SVUH. The intercenter correlation for the pooled scores of sections stained at AMC was R = 0.85, p = 0.000, and for the sections stained at SVUH, R = 0.62, p = 0.001. The consistent correlation between DeltaDAS (Disease Activity Score) and DeltaCD68sl expression across different studies (Pearson correlation = 0.895, p < 0.001) was confirmed. The standardized response mean values for DeltaCD68sl, calculated from analyses at both AMC and SVUH, were consistently 0.5 or greater, indicating a moderate to high potential to detect change. CONCLUSION: The correlation between mean DeltaDAS and mean DeltaCD68sl expression was confirmed across 2 centers. Examination of serial biopsy samples can be used reliably to screen for interesting biological effects at the site of inflammation at an early stage of drug development.
Language:
eng
MeSH:
Antibodies, Monoclonal/therapeutic use; Antibodies, Monoclonal, Murine-Derived; Antigens, CD/*metabolism; Antigens, Differentiation, Myelomonocytic/*metabolism; Antirheumatic Agents/therapeutic use; Arthritis, Rheumatoid/*drug therapy/metabolism/pathology; Biological Markers/*metabolism; Biopsy; Clinical Trials as Topic/*methods/*standards; Drug Monitoring/methods/standards; Humans; Macrophages/pathology; Reproducibility of Results; Synovial Membrane/metabolism/pathology
ISSN:
0315-162X (Print); 0315-162X (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorBresnihan, Barryen_GB
dc.contributor.authorPontifex, Elizaen_GB
dc.contributor.authorThurlings, Rogier Men_GB
dc.contributor.authorVinkenoog, Marjoleinen_GB
dc.contributor.authorEl-Gabalawy, Hanien_GB
dc.contributor.authorFearon, Ursulaen_GB
dc.contributor.authorFitzgerald, Oliveren_GB
dc.contributor.authorGerlag, Danielle Men_GB
dc.contributor.authorRooney, Terenceen_GB
dc.contributor.authorvan de Sande, Marleen Gen_GB
dc.contributor.authorVeale, Douglasen_GB
dc.contributor.authorVos, Koenen_GB
dc.contributor.authorTak, Paul-Peteren_GB
dc.date.accessioned2012-02-01T10:29:17Z-
dc.date.available2012-02-01T10:29:17Z-
dc.date.issued2012-02-01T10:29:17Z-
dc.identifier.citationJ Rheumatol. 2009 Aug;36(8):1800-2.en_GB
dc.identifier.issn0315-162X (Print)en_GB
dc.identifier.issn0315-162X (Linking)en_GB
dc.identifier.pmid19671815en_GB
dc.identifier.doi10.3899/jrheum.090348en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207489-
dc.description.abstractOBJECTIVE: To determine whether the correlation between the mean change in disease activity and the mean change in synovial sublining (sl) CD68 expression could be demonstrated across different academic centers. METHODS: Synovial biopsies obtained at arthroscopy from patients with rheumatoid arthritis before and 160 days after rituximab therapy were selected and coded. Paired sections were processed independently at Amsterdam Medical Center (AMC) and at St. Vincent's University Hospital (SVUH), Dublin. Digital image analysis (DIA) was employed at both centers to quantify sublining CD68 expression. RESULTS: After analysis of CD68sl expression at centers in 2 different countries, high levels of intracenter and intercenter agreement were observed. For the pooled sections stained at AMC, the correlation between 2 investigators was R = 0.942, p = 0.000, and for sections stained at SVUH, R = 0.899, p = 0.001. Similarly, the intracenter correlations for DeltaCD68sl expression after treatment were R = 0.998, p = 0.000, for sections stained at AMC and R = 0.880, p = 0.000, for sections stained at SVUH. The intercenter correlation for the pooled scores of sections stained at AMC was R = 0.85, p = 0.000, and for the sections stained at SVUH, R = 0.62, p = 0.001. The consistent correlation between DeltaDAS (Disease Activity Score) and DeltaCD68sl expression across different studies (Pearson correlation = 0.895, p < 0.001) was confirmed. The standardized response mean values for DeltaCD68sl, calculated from analyses at both AMC and SVUH, were consistently 0.5 or greater, indicating a moderate to high potential to detect change. CONCLUSION: The correlation between mean DeltaDAS and mean DeltaCD68sl expression was confirmed across 2 centers. Examination of serial biopsy samples can be used reliably to screen for interesting biological effects at the site of inflammation at an early stage of drug development.en_GB
dc.language.isoengen_GB
dc.subject.meshAntibodies, Monoclonal/therapeutic useen_GB
dc.subject.meshAntibodies, Monoclonal, Murine-Deriveden_GB
dc.subject.meshAntigens, CD/*metabolismen_GB
dc.subject.meshAntigens, Differentiation, Myelomonocytic/*metabolismen_GB
dc.subject.meshAntirheumatic Agents/therapeutic useen_GB
dc.subject.meshArthritis, Rheumatoid/*drug therapy/metabolism/pathologyen_GB
dc.subject.meshBiological Markers/*metabolismen_GB
dc.subject.meshBiopsyen_GB
dc.subject.meshClinical Trials as Topic/*methods/*standardsen_GB
dc.subject.meshDrug Monitoring/methods/standardsen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMacrophages/pathologyen_GB
dc.subject.meshReproducibility of Resultsen_GB
dc.subject.meshSynovial Membrane/metabolism/pathologyen_GB
dc.titleSynovial tissue sublining CD68 expression is a biomarker of therapeutic response in rheumatoid arthritis clinical trials: consistency across centers.en_GB
dc.contributor.departmentSt. Vincent's University Hospital, Dublin, Ireland. barry.bresnihan@gmail.comen_GB
dc.identifier.journalThe Journal of rheumatologyen_GB
dc.description.provinceLeinster-

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