title: Synovial tissue sublining CD68 expression is a biomarker of therapeutic response in rheumatoid arthritis clinical trials: consistency across centers.
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.
  
  
  CONCLUSIONS
  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.
authors: St. Vincent's University Hospital, Dublin, Ireland. barry.bresnihan@gmail.com
authors: Barry
authors: B
authors: Bresnihan
authors: Eliza
authors: E
authors: Pontifex
authors: Rogier M
authors: RM
authors: Thurlings
authors: Marjolein
authors: M
authors: Vinkenoog
authors: Hani
authors: H
authors: El-Gabalawy
authors: Ursula
authors: U
authors: Fearon
authors: Oliver
authors: O
authors: Fitzgerald
authors: Danielle M
authors: DM
authors: Gerlag
authors: Terence
authors: T
authors: Rooney
authors: Marleen G
authors: MG
authors: van de Sande
authors: Douglas
authors: D
authors: Veale
authors: Koen
authors: K
authors: Vos
authors: Paul-Peter
authors: PP
authors: Tak
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism*; D001706:Biopsy; D002986:Clinical Trials as Topic / Q000379:methods* / Q000592:standards*; D016903:Drug Monitoring / Q000379:methods / Q000592:standards; D006801:Humans; D008264:Macrophages / Q000473:pathology; D015203:Reproducibility of Results; D000069283:Rituximab; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D000097382:CD68 Molecule
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018501:Antirheumatic Agents; D015415:Biomarkers; D000069283:Rituximab; C067980:CD68 antigen, human; D000097382:CD68 Molecule