P650 Mechanisms of Infliximab failure: the predictive role of MMP3
B. Barberio*1, R. D'Incà2, S. Facchin3, M. Dalla Gasperina1, C. Fohom1, R. Cardin1, E. Savarino2, F. Zingone1
1Dr., Gastroenterology, Padova, Italy, 2University of Padua, Department of Oncological Gastrointestinal Surgery, Padova, Italy, 3University of Padua, Department of Surgery, Oncology and Gastroenterology, Gastroenterology Section, Padova, Italy
Recently, further pathways of degradation of anti-TNF therapies have been hypothesised such as the presence of activated metalloproteinases (MMPs), particularly MMP3, which seem to cleave the IgG1 and neutralise the drug activity. However, no data to have been published evaluating whether levels of MMP3 can be associated to anti-TNF failure in patients with inflammatory bowel disease (IBD) in a longitudinal study.
Retrospectively, we included 73 IBD patients (37 UC, 36 CD) responder (R 37) and non-responder (NR 36) to infliximab therapy after 52 weeks of treatment and who had started biologic therapy because of moderate-to-severe clinical activity at baseline (T0). Patients underwent MMP3 dosage at baseline, post induction (TPI), and at 12 months (T12). In addition, trough level (TL) and anti-drug antibody (ATI) values were also determined at t12. For comparison, MMP3 levels were determined in 28 healthy subjects as controls. Demographic and clinical features were recorded, including BMI, HBI/Mayo score, endoscopy score, CRP, faecal calprotectin, and albumin. We used medians with inter-quartile for continuous data and percentages for discrete data. Chi-square test and Mann–Whitney
Serum levels of MMP3 between R and NR were not statistically significant at T0 (
High MMP3 levels at post-induction predict loss of response over the next 12 months. Patients NR to Infliximab therapy, both with high ATI and low ATI, have high MMP3 levels; higher MMP3 levels correspond to lower TL.