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P607 Infliximab trough levels and anti-drug antibodies after induction predict long-term clinical remission in infliximab-treated patients with inflammatory bowel disease

G. Bodini*1, L. Del Nero1, E. G. Giannini1, S. Tolone2, N. De Bortoli3, J. Anjali4, I. Baldissarro1, V. Savarino1, E. Savarino5

1University of Genoa, Internal medicine department, Genoa, Italy, 2Second University of Naples, Department of surgery, Naples, Italy, 3University of Pisa, Internal medicine department, gastroenterology unit, Pisa, Italy, 4Prometheus Laboratories, Department of Research and Development, San Diego, California, United States, 5University of Padua, Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, Padua, Italy

Background

The treatment paradigm of Inflammatory Bowel Disease is dramatically changed in the past decades, thanks to the development of biological drugs. However, approximately 40% of primary responder patients to anti-TNF therapy experience a loss of response (LOR) during the first year of treatment. Recently, drugs trough levels (TL) and anti-drug antibodies (ADA) presence were proposed as useful tools in the management of patients who have a LOR. Currently, one of the most important issue in IBD patients on biological therapy is to timely identify patients at risk of anti-TNF therapy failure.

Methods

The aim of our prospective study was to evaluate TL and ADA presence after Infliximab (IFX) induction and their correlation with clinical activity in a series of patients with Inflammatory Bowel Disease (IBD) followed-up for at least 48 weeks. We included 32 consecutive Inflammatory Bowel Disease patients [20 Crohn’s Disease (CD) and 12 Ulcerative Colitis (UC); 17 males, median age 42 years, range 186– 9] who underwent IFX therapy and achieved clinical remission after induction (schedule: 5 mg/kg at week 0, 2 and 6). Blood samples were drawn at standardised time points (ie, 0, 2, 6, and 14 week) before IFX infusion. TL and IFX ADA were measured using a homogenous mobility shift assay (HMSA; Prometheus Lab, San Diego, California, United States). Disease activity was assessed both at week 14 and week 48 by the Harvey–Bradshaw Index (HBI, remission defined by HBI<5) in CD patients and by the Mayo score for UC patients (remission defined by Mayo score <2). In addition, C-reactive protein and erythrocyte sedimentation rate (ESR) were measured.

Results

During 48 weeks follow-up, 14 patients (43.8%) experienced LOR. We found significantly lower IFX TL after induction in patients who experienced LOR as compared with patients who maintained clinical remission during the follow-up period (0.78 mcg/ml, range 0–14.97 mcg/ml versus 10.01 mcg/ml, range 0.00–42.83 mcg/ml; p = 0.0018). Moreover, IFX TL were significantly lower in ADA positive patients as compared with ADA negative ones (0 mcg/ml, range 09– .66 mcg/ml versus 11.91 mcg/ml, range 2.00– 42.83 mcg/ml; p < 0.0001). Lastly, ADA concentration after induction was significantly higher in relapsers as compared with patients in remission (3.13 U/ml, range 0–30.52 U/ml versus 0 U/ml, range 0–16.83 U/ml; p = 0.02).

Conclusion

Patients who experienced LOR to IFX monotherapy during long-term follow-up (48 weeks) had significantly lower IFX TL and higher ADA serum concentrations after IFX induction (i.e., 14 weeks). Therefore, assessment of IFX TL and of ADA serum concentrations after IFX induction can be used as a predictive tool for estimating the long-term clinical response to biological therapy.