Early effects of rituximab on the synovial cell infiltrate in patients with rheumatoid arthritis.
OBJECTIVE
To study the specific effects of rituximab treatment on the synovium in patients with rheumatoid arthritis (RA) early after initiation of treatment.


METHODS
Seventeen RA patients underwent an arthroscopic synovial biopsy procedure directly before and 1 month after receiving 2 infusions of the chimeric anti-CD20 monoclonal antibody rituximab (1,000 mg on days 1 and 15; both without methylprednisolone premedication). Immunohistochemical analysis was performed to characterize the cell infiltrate. Stained tissue sections were analyzed by digital image analysis. Statistical analysis was performed using Wilcoxon's signed rank test.


RESULTS
No significant change in the Disease Activity Score 28-joint assessment was found at 4 weeks after the first rituximab infusion. At 2 and 4 weeks after infusion, B cells in peripheral blood were almost completely depleted. Most B cells in the synovium were found in large lymphocyte aggregates. Interestingly, a significant reduction in B cell numbers at sites of inflammation was observed 4 weeks after treatment (median 26 cells/mm(2) [interquartile range 4-150] before treatment and 11 cells/mm(2) [interquartile range 0-29] after treatment; P < 0.02). B cells disappeared completely in 3 patients, whereas there was partial depletion in 11 patients. In the other 3 patients, no B cells were present in biopsy tissues obtained either pretreatment or posttreatment. No reductions in other synovial cell populations were observed at 4 weeks.


CONCLUSIONS
Rituximab treatment leads to a rapid and significant decrease in synovial B cell numbers, but not in all patients. Whether the variable tissue response is related to the clinical response over time remains to be clarified.
Vos
Koen
K
Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands. k.vos@amc.uva.nl
Thurlings
Rogier M
RM
Wijbrandts
Carla A
CA
van Schaardenburg
Dirkjan
D
Gerlag
Daniëlle M
DM
Tak
Paul P
PP
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000473:pathology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology; D001706:Biopsy; D002452:Cell Count; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000187:drug effects* / Q000473:pathology
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D000069283:Rituximab