P356. Loss of efficacy and adverse drug reactions during infliximab therapy in IBD patients are related to the appearance of anti-infliximab antibodies

A. Settesoldi1, M. Giannotta1, M. Milla1, S. Genise1, A. Santini1, S. Bagnoli1, V. Annese1, A. Matucci2, A. Vultaggio2, G. Petroni2, S. Pratesi2, F. Nencini2, E. Maggi2

1AOU Careggi, SOD Gastroenterologia, Florence, Italy; 2AOU Careggi, Dipartimento di Biomedicina – Unità di Immunoallergologia, Florence, Italy

Background: Infliximab is a chimeric monoclonal antibody against TNF-alpha useful in the treatment of many immuno-mediated inflammatory diseases including IBD. Unfortunately some patients may experience adverse drug reactions (ADR) or loss of efficacy during treatment and this could be related to infliximab immunogenicity and development of specific antibodies.

Methods: Fifty-three consecutive patients suffering from active CD (n = 21) or UC (n = 32) were enrolled and treated with infliximab because resistant to traditional therapies. Patients were defined as responder, non-responder (including primary and secondary non-responders) or intolerant to treatment depending on clinical outcome and the occurrence of ADR. Sera for the detection of anti-infliximab antibodies (ATI) were collected before each infusion and eventually after any ADR or at loss of efficacy. Non isotype-specific ATI were measured by a double-capture ELISA kit (Immundiagnostick AG) according to the manufacturer's instructions. Sera were considered to be positive when exceeded the cut off value [twice the optical density (OD) of the negative control]. A chi-squared test was used to analyse patients groups and a p < 0.05 value was considered as significant.

Results: ATI resulted positive in 19 out of 53 enrolled patients (35.8%). Serum ATI were detected in a significantly higher proportion of intolerant patients (8 out of 8, 100%, p < 0.0001) and non-responders (6 out of 11, 75%, p < 0.05) compared to responders (5 out of 36, 13.8%). The ATI frequency was significantly higher in intolerant compared to non-responder patients (p < 0.02). ATI positivity was found in 3 responder patients without ADR. In secondary non-responders and intolerant patients the appearance of ATI had a strict timing relationship.

Conclusions: Although the investigation of antibodies against infliximab may not reflect the full extent of immunogenicity of this molecule, our results show that in a consistent proportion of cases both loss of efficacy and infliximab related ADR were associated with the appearance of ATI with a strict timing relationship. Future management of biologics in IBD should include measurement of anti-drug antibodies in order to potentially avoid inappropriate therapy and to optimize treatment.