P253. Transient versus sustained antibodies to infliximab: Possibility to overcome low titer antibody responses by dose optimisation
N. Vande Casteele1, L. Cuypers1, S. Singh2, S. Hauenstein2, L. Ohrmund2, E. Chuang2, P. Rutgeerts3, A. Gils1, S. Vermeire3
1Katholieke Universiteit Leuven, Laboratory for Pharmaceutical Biology, Belgium; 2Prometheus Laboratories, San Diego, United States; 3University Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium
Background: Infliximab (IFX) can provoke an immunogenic response in Inflammatory Bowel Disease (IBD) patients which leads to loss of response to the drug. It is generally believed that, once elicited, an antibody response to a certain protein cannot be overcome. We hypothesised that in patients who elicit only low levels of antibodies to infliximab (ATI), these may disappear with dose optimisation and that patients may recapture response.
Methods: In this retrospective analysis in 57 IFX-treated patients a total of 788 serum samples (average of 13.8 samples per patient) were analysed. Patients were selected based on ATIs detected on at least one time point during follow up with an in-house developed bridging ELISA. All samples were then analysed for IFX trough levels (TLI) and ATIs using a fluid phase mobility shift assay (Prometheus Laboratories, San Diego US). Treatment decisions to optimise and stop therapy were made on clinical grounds and CRP and not on ATI or TLI. All data are expressed as (median; Q1-Q3).
Results: Patients had developed ATIs (14; 732) weeks after start of IFX, or after (4; 26) infusions. In 19 (33%) patients ATIs disappeared over time whereas in 38 (67%) patients ATIs persisted. There was no difference in time to ATI formation between both groups. Before the second infusion 20% of patients who developed later on persisting ATIs had an undetectable TLI versus 0% of patients who developed transient ATIs. Patients with transient ATIs had significantly lower ATI levels (6; 3.112.2 U/ml) compared to patients with sustained ATIs (18; 8.734.8 U/ml). In patients with transient ATIs CRP decreased from (25; 5.555.3 mg/l) when ATIs were first detected to (8; 2.918.2 mg/l) when ATIs disappeared. Concomitant IMM use was associated with less ATI formation: (7; 3.919.1 U/ml) with IMM vs. (14; 6.227.5 U/ml) without IMM. In 11/19 patients (58%) with transient ATIs these disappeared following dose optimisation and in 8/19 patients (42%) ATIs disappeared spontaneously. Sustained ATIs more often lead to treatment discontinuation (74%) as compared to transient ATIs (26%).
Conclusions: Antibodies to infliximab may be transient and can disappear after dose optimisation. Sustained high levels of ATIs lead however to permanent loss of response. When low or undetectable TLI are detected measuring ATIs is necessary. Low titre ATIs can be overcome by treatment optimisation. High ATIs necessitate treatment stop.