Clinical response, pharmacokinetics, development of human anti-chimaeric antibodies, and synovial tissue response to rituximab treatment in patients with rheumatoid arthritis.
OBJECTIVE
To analyse whether persistence of synovial B lineage cells and lack of clinical response to rituximab treatment in patients with rheumatoid arthritis (RA) are associated with low rituximab serum levels and anti-rituximab antibody (ARA) formation.


METHODS
Fifty-eight patients with RA were treated with rituximab. The clinical response was determined 24 weeks after each treatment course using the Disease Activity Score evaluated in 28 joints (DAS28) and EULAR response criteria. Rituximab serum levels, ARAs and synovial B lineage cell numbers were determined before and after treatment.


RESULTS
Four weeks after treatment rituximab serum levels were highly variable. Low rituximab levels were associated with ARA formation (in five patients (8.6%)) and high baseline erythrocyte sedimentation rate. Interestingly, serum rituximab levels were not related to persistence of synovial B lineage cells or clinical response. Furthermore, response to treatment and re-treatment was similar in ARA-positive and ARA-negative patients.


CONCLUSIONS
There is clear variability in serum levels after rituximab treatment, but rituximab levels are not lower in patients with persistence of synovial B lineage cells or lack of clinical response. The current treatment schedule suffices to induce and maintain a clinical response, even when ARAs are formed.
Thurlings
R M
RM
Academic Medical Centre/University of Amsterdam, The Netherlands.
Teng
O
O
Vos
K
K
Gerlag
D M
DM
Aarden
L
L
Stapel
S O
SO
van Laar
J M
JM
Tak
P P
PP
Wolbink
G J
GJ
D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D000069283:Rituximab; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000276:immunology*; D016896:Treatment Outcome
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab