The immunogenic part of infliximab is the F(ab ')(2), but measuring antibodies to the intact infliximab molecule is more clinically useful

Objectives To localise the immunogenic part of infliximab and evaluate the clinical usefulness of measuring antibodies against infliximab fragments. Design Observational study. Settings A specialised inflammatory bowel disease (IBD) centre in a tertiary hospital. Interventions Serum was collected from patients with IBD and controls. Antibodies against whole infliximab (ATI) and against the digested Fc, F(ab`)(2) and F(ab`) fragments were measured by a specifically developed ELISA and by western blotting. A separate ELISA was used to determine infliximab levels in serum. Results 109 serum samples from 62 infliximab-treated patients were tested along with 64 control samples. Anti-F(ab`)(2) antibodies were found in 28/42 (67%) samples with positive ATI, all from infliximab-exposed patients. Anti-F(ab`)(2) antibodies were also present in 26 of the remaining 67 (39%) samples from exposed patients despite absent ATI. No specific anti-Fc antibodies were detected. Low trough infliximab level and high ATI level was found in 10/12 patients (83%) with complete loss of response to infliximab, but in only 5/14 patients (36%, p=0.02) who regained response to intensified infliximab regimen and in 2/24 patients (8%, p < 0.001) in maintained remission while on 5 mg/kg/8 week infliximab treatment. Although Anti-F(ab`) 2 antibodies showed similar test characteristics to ATI in patients losing response to infliximab, they were also detected in 61% of patients in maintained remission, thereby limiting their clinical usefulness. No cross reactivity to adalimumab was noted. Conclusions F(ab`)(2) is the immunogenic fragment of infliximab. However, ATI level in serum-combined with measurement of trough infliximab level-is better correlated with the clinical response to infliximab or with its loss.