S955 Effectiveness of Vedolizumab in Patients With Inflammatory Bowel Disease and Concomitant Primary Sclerosing Cholangitis

Abstract

Introduction: Patients with concomitant primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) are known to have a unique clinical phenotype (PSC-IBD), including higher expression of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) in both liver and intestinal tissues. MADCAM-1 interacts with α4β7 integrin to allow access of lymphocytes to the intestinal mucosa and is inhibited by vedolizumab (VDZ). Although VDZ has not been shown to slow progression of PSC, little is known about its impact in intestinal inflammation of PSC-IBD patients. We aimed to report the effectiveness of VDZ in controlling intestinal inflammation in a large PSC-IBD cohort. Methods: We conducted a retrospective review of patients with PSC-IBD treated with VDZ from January 2009 to January 2019. Demographic, clinical, endoscopic, and radiologic data were abstracted at baseline, and at 6 and 12 months after initiation of VDZ. Outcomes of interest included: clinical response, radiologic response and healing, endoscopic response, mucosal healing, and histologic healing. Results: A total of 108 patients with PSC-IBD treated with VDZ were identified. The majority were male (66%), with median age of 45 years (range, 19 -83). The most common IBD subtype was ulcerative colitis (UC) (61.1%), followed by Crohn’s disease (CD) (33.3%), and indeterminate colitis (5.6%). Median disease duration at the start of VDZ was 8 years (range, 0-50), with ileocolonic CD (85.3%) and pancolitis (92.2%) as the predominant disease locations. Over three quarters of the cohort (79.6%) had previously failed other biologic therapy (Table). VDZ was most often dosed every 8 weeks (73.1%) and the median duration of VDZ therapy was 17.5 months (range, 2-66). Clinical response was 72.6% at 6 months and 77.1% at 1 year. Among patients who had follow-up endoscopy, endoscopic response was noted in 47.1% and 58.1% of the cases at 6 months and 1 year, respectively. Radiologic response at 6 months and 1 year was 32.4% and 38.9%, respectively. Radiology healing at 6 months and 1 year was 16.2% and 18.2%, respectively. Histologic healing at 6 months was 6.7% and 18.8% at 1 year. Conclusion: VDZ is effective in the management of intestinal inflammation in patients with PSC-IBD, with clinical and endoscopic outcomes at 1-year follow-up comparable to currently available clinical trials in non-PSC patients. Further studies comparing outcomes of PSC-IBD patients on VDZ to other biologic therapies are needed. Table 1. - Patient Demographics and Vedolizumab Outcomes Patient demographics N = 108 Male, n (%) 72 (66.7) Median age, years (range) 45 (19-83) Median disease duration, years (range) 8 (0-50) Prior use of other biologics, n (%) 86 (79.6) Combination therapy while on VDZ, n (%) Thiopurine/6MP/azathioprine 18 (17.3) Methotrexate 1 (1.0) IBD Subtype, n (%) CD 36 (33.3) UC 66 (61.1) Indeterminate colitis 6 (5.6) CD Location, n (%) Terminal ileum 0/34 (0) Colon 4/34 (11.8) Ileocolonic 29/34 (85.3) Upper GI 1/34 (2.9) Perianal disease, n (%) 9 (8.8) CD phenotype, n (%) Inflammatory 16/36 (44.4) Stricturing 14/36 (38.9) Penetrating 6/36 (16.7) UC extension, n (%) Proctitis 3/64 (4.7) Left sided colitis 2/64 (3.1) Pancolitis 59/64 (92.2) Bowel resection before VDZ, n (%) 45 (55.6) History of liver transplant, n (%) 33 (30.6) VDZ outcomes N = (108) Median duration of therapy, months (range) 17.5 (2.0-66.0) Drug dose frequency, n (%) Every 8 weeks 79 (73.1) Every 6 weeks 7 (6.5) Every 4 weeks 22 (20.4) VDZ discontinued indefinitely, n (%) 46 (43.0) Clinical response at 6 months, n (%) 74/102 (72.6) Clinical response at 1 year, n (%) 64/83 (77.1) Endoscopic response at 6 months, n (%) 24/51 (47.1) Endoscopic healing at 6 months, n (%) 8/55 (14.5) Endoscopic response at 1 year, n (%) 25/43 (58.1) Endoscopic healing at 1 year, n (%) 12/46 (26.1) Radiologic response at 6 months, n (%) 11/34 (32.4) Radiologic healing at 6 months, n (%) 6/37 (16.2) Radiologic response at 1 year, n (%) 7/18 (38.9) Radiologic healing at 1 year, n (%) 4/22 (18.2) Histologic healing at 6 months, n (%) 3/45 (6.7) Histologic healing at 1 year, n (%) 9/48 (18.8) Colectomy on VDZ, n (%) 16/108 (15.0)