P655 MadCAM1 Negativity of Lamina Propria Endothelial Cells is Associated with Non-Response to Vedolizumab in Inflammatory Bowel Disease Patients

Zelinkova, Z.(1)*;Podmanicky, D.(2);Berakova, K.(3);Kadleckova, B.(1);

(1)Nemocnica Bory - Penta Hospitals, Department of Gastroenterology, Bratislava, Slovakia;(2)Nemocnica Bory - Penta Hospitals, Department of Surgery, Bratislava, Slovakia;(3)Martinske Biopticke Centrum, Department of Pathology, Zilina, Slovakia;

Background

Vedolizumab (VDZ), a monoclonal antibody against α4β7 integrin has been shown to be effective in inducing and maintaining remission in inflammatory bowel disease (IBD). By blocking α4β7, it is preventing the homing of lymphocytes through binding to mucosal vascular adressin cell adhesion molecule 1 (MadCAM1) localised on the intestinal endothelial cells. We have previously reported that MadCAM1 is expressed to various extent on lamina propria endothelial cells of IBD patients and that this expression is stable over time. The aim of the present study was to analyse whether expression of MadCAM1 was related to the response to VDZ in IBD patients.

Methods

All IBD patients treated with VDZ in one referral IBD centre were included. The biopsies or resection specimen from the inflamed intestinal tissue were stained by immunohistochemistry for MadCAM1 expression. Clinical response to vedolizumab was assessed in patients with the minimal treatment duration of 10 weeks and the response rate between patients with positive and negative MadCAM1 were analyzed by Fisher`s exact test.

Results

In total, 92 IBD patients were treated with VDZ; for 83 of them intestinal biopsies or surgical specimen were available for assessment of MadCAM1 expression. In four patients (5%) no expression of MadCAM1 was detected, remaining 79 patients expressed MadCAM1 to various extent.

Overal, 30 patients (36%) were non-responders to VDZ treatment. With regards to MadCAM1 expression, 67% of patients expressing MadCAM1 responded to VDZ (53 patients) while none of the patients negative for MadCAM1 responded to treatment (p=0.0171).

Conclusion

Lack of MadCAM1 expression in intestinal endothelium is associated with clinical non-response to vedolizumab.