Synovial tissue sublining CD68 expression is a biomarker of therapeutic response in rheumatoid arthritis clinical trials: consistency across centers.
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.
Bresnihan
Barry
B
St. Vincent's University Hospital, Dublin, Ireland. barry.bresnihan@gmail.com
Pontifex
Eliza
E
Thurlings
Rogier M
RM
Vinkenoog
Marjolein
M
El-Gabalawy
Hani
H
Fearon
Ursula
U
Fitzgerald
Oliver
O
Gerlag
Danielle M
DM
Rooney
Terence
T
van de Sande
Marleen G
MG
Veale
Douglas
D
Vos
Koen
K
Tak
Paul-Peter
PP
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
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