Development of antiinfliximab antibodies and relationship to clinical response in patients with rheumatoid arthritis.
OBJECTIVE
Treatment of patients with infliximab, a chimeric monoclonal IgG1 antibody against tumor necrosis factor, may result in the formation of infliximab-specific IgG antibodies. This study evaluated the clinical significance of these antibodies in patients with rheumatoid arthritis (RA).


METHODS
Antiinfliximab antibodies were measured using a newly developed radioimmunoassay in a cohort of 51 consecutive patients with RA treated with infliximab, with a followup of 1 year. In addition, serum infliximab levels were determined by enzyme-linked immunosorbent assay. The results were analyzed in relation to the clinical response to treatment according to the European League Against Rheumatism criteria.


RESULTS
Antibodies against infliximab were detected in 22 patients (43%). Patients without detectable antiinfliximab antibodies (n = 29 [57%]) were significantly more often classified as responders (20 of 29 [69%]) compared with patients with detectable antiinfliximab antibodies (8 of 22 [36%]; P = 0.04). Three patients had an infusion-related allergic reaction, all of whom had detectable antiinfliximab antibodies.


CONCLUSIONS
In this study, nearly half of the RA patients treated with infliximab developed antiinfliximab antibodies within the first year of treatment. This seems to be clinically relevant, since development of antiinfliximab antibodies is associated with a reduced response to treatment.
Wolbink
Gerrit Jan
GJ
Department of Immunopathology, CLB Sanquin Amsterdam and Jan van Breeman Institute, Amsterdam, The Netherlands. G.Wolbink@janvanbreeman.nl
Vis
Marijn
M
Lems
Willem
W
Voskuyl
Alexandre E
AE
de Groot
Els
E
Nurmohamed
Michael T
MT
Stapel
Steven
S
Tak
Paul P
PP
Aarden
Lucien
L
Dijkmans
Ben
B
D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use*; D000917:Antibody Formation; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D011863:Radioimmunoassay
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000069285:Infliximab