Anti-infliximab Antibodies in RA Patients Treated with Infliximab.

Gerrit J. Wolbink1, Willem F. Lems2, Michel T. Nurmohamed1, Marijn Vis3,
Alexandre E. Voskuyl3, Steven Stapel4, Els de Groot4, Paul P. Tak5, Ben
A. Dijkmans3, Lucien Aarden4. 1Jan van Breemen Instituut, Amsterdam,
Netherlands; 2Slotervaart Hospital, Amsterdam, Netherlands; 3Vu-medical
Center, Amsterdam, Netherlands; 4Sanquin Research, Amsterdam,
Netherlands; 5Amsterdam Medical Center/UVA, Amsterdam, Netherlands

Purpose: To evaluate the prevalence and clinical significance of
anti-infliximab antibodies in patients with rheumatoid arthritis.

Methods: We developed a radioimmunoassay for the detection of
anti-infliximab antibodies in serum and used this assay for
retrospective evaluation of the presence of anti-infliximab antibodies
in sera, collected prior to each infliximab infusion, from 50
consecutive RA patients with a follow-up of one year. Patients had been
treated according to the consensus statement on the initiation and
continuation of TNF blocking therapies in rheumatoid arthritis.
Infliximab had been given as a 3mg/kg infusion at 0, 2, 6 and every
eight weeks thereafter.In patients with insufficient response the
infliximab dosage had been increased to 7,5 mg/kg every eight weeks.

44 patients used concomitant MTX at a median dose of 15 mg/week, 3
patients azathioprine and 1 patient cyclosporine. Results: Antibodies to
infliximab were detected in 22 (44 %) of the patients.

From the patients who developed anti-infliximab antibodies only 41 % was
still on standard treatment with 3mg/kg infliximab infusions after one
year of therapy. From the patients who did not develop anti-infliximab
antibodies 79 % was treated with 3 mg/kg infliximab infusions after 1
year.

Conclusion: The results of this study suggest that the development of
antibodies against infliximab in rheumatoid arthritis patients is
associated with reduced response to therapy.
no anti-infliximab antibodies detected
n=28tested positive for anti-infliximab antibodies
n=22on treatment with with 3 mg/kg infusions afer one year22 (79%)9
(41%)on treatment with with 7,5 mg/kg infusions after one year38stopped
treatment with infliximab before the end of the first year of therapy.