There is no Difference in Short-Term Colectomy Rate between Infliximab-Exposed and Infliximab-Naïve Hospitalized Ulcerative Colitis Patients

AGA Abstracts

Sa1927

Sa1929

EFFICACY OF VEDOLIZUMAB ON EXTRAINTESTINAL MANIFESTATION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES: A POST-HOC ANALYSIS OF THE OBSERV-IBD COHORT OF THE GETAID Sara Tadbiri, Jean-charles Grimaud, Laurent Peyrin-Biroulet, Jerome Filippi, Benjamin Pariente, Xavier Roblin, Anthony Buisson, Carmen Stefanescu, Caroline Trang, Romain Altwegg, Philippe R. Marteau, Thibaut Vaysse, Anne Bourrier, David Laharie, Matthieu Allez, Yoram Bouhnik, Aurelien Amiot

EFFECTIVENESS AND SAFETY OF CT-P13 UNDER ROUTINE CARE IN PEDIATRIC PATIENTS WITH INFLAMMATORY BOWEL DISEASE Yon Ho Choe, Hye Ran Yang, Jin Soo Moon, Eell Ryoo, Seung Kim, Ji Hyun Lee, HyoJong Kim, Jae Hong Park, Mi Jin Kim, Sang Joon Lee, Sung Young Lee Background: Biosimilar to innovator infliximab (INX), CT-P13, has been approved for all indications including pediatric patients with inflammatory bowel disease (IBD) by the European Medicines Agency in 2013 and Food and Drug Administration in 2016. Observational study has been conducted for pediatric patients with Crohn's disease (CD) or Ulcerative colitis (UC) at 10 study centers in South Korea. Methods: Pediatric CD and UC patients were classified as naïve patients or switch patients defined by history of treatment with antiTNF agents prior to receiving CT-P13. For CD patients, remission was defined by Pediatric Crohn's Disease Activity Index (PCDAI) score of less than 10 (Hyams et al. 20051). For UC patients, remission was defined by Pediatric Ulcerative Colitis Activity Index (PUCAI) score of less than 10 (Turner et al. 20122). Effectiveness was considered as post-baseline remission if at least one remission was achieved throughout Week 2 to 30. Results: A total of 51 pediatric patients with CD (26 naïve patients and 25 switch patients) and 23 pediatric patients with UC (16 naïve and 7 switch patients) were included. Pediatric CD population consisted of 25 male and 26 female patients with mean age of 14.3±2.4 years. For pediatric UC, 11 male and 12 female patients were included with mean age of 13.6±3.0 years. At baseline, disease status of naïve patients was 4 times higher than switch patients when comparing baseline PCDAI or PUCAI score. The proportion of patients achieving postbaseline remission was 87.5% (21/24) and 80.0% (12/15) for naïve CD and UC patients, respectively. For switch group, post-baseline remission was achieved in 86.4% (19/22) and 100.0% (7/7) of CD and UC patients, respectively. Overall, 2 (6.3% [2/32]) switch patients experienced at least 1 related treatment-emergent adverse event (TEAE) (for CD, 4.0% [1/ 25]; for UC, 14.3% [1/7]). And no related TEAE was observed in naïve patients. There were total 4 (9.5% [4/42]) naive patients and 1 (3.1% [1/32]) switch patient reported treatmentemergent serious adverse event (TESAE) but none of them were considered related to treatment by investigator. Infusion-related reaction was reported in 1 (3.1% [1/32]) switch patient and there were no cases from naïve patients. Conclusion: CT-P13 in both naïve and switch pediatric patients with IBD was effective over 30 weeks. The safety of CT-P13 was favourable and product was well tolerated in pediatric IBD population. 1. Hyams et al. JPGN. 2005; 41:416-421 2. Turners et al. JPGN. 2012;55: 340-361 Table 1: Post-Baseline Remission by PCDAI and PUCAI

Introduction: Up to 50% of patients with inflammatory bowel disease (IBD) experience at least one extraintestinal manifestation (EIM). Vedolizumab (VDZ) is a humanized monoclonal antibody that specifically antagonizes α4β7 integrin in a gut-specific manner. Whether or not VDZ is effective on EIM needs to be assessed. Patients and Methods: Between June and December 2014, 173 patients with Crohn's disease (CD) and 121 with ulcerative colitis (UC) were included in the OBSERV-IBD cohort study and followed up during a 54-week period. Efficacy of vedolizumab on EIM was estimated by using a 3-step scale: (1) complete remission meaning absence or almost absence of all clinical symptoms without increasing the steroid dose or introducing any other IBD-specific treatment (2) partial response meaning improvement of symptoms or reduction of the steroid dose without worsening of symptoms (3) no response, meaning no improvement or worsening of symptoms. Results: Among the 294 patients with IBD, 50 (17.2%) presented with EIM at baseline including 46 (15.6%) with arthropathies and 5 (1.7%) with skin manifestations. At week 14, complete remission was observed in 24 (52.2%) patients with arthropathies and in 4 (80%) patients with skin manifestation. At week 54, 21 (45.7%) and 3 (60%) were still in complete remission for athropathies and skin manifestations, respectively. During the follow-up period, 32 (15.8%) patients without any EIM at baseline, presented with arthropathies. The probabilities of developing arthropathies during VDZ therapy was 5.2%, 10% 13.9% and 17.5% at weeks 14, 22, 30 and 54, respectively. In multivariate analysis, predictors of arthropathies occurrence were prior ankylosing spondylitis and Crohn's disease. During the follow-up period, 14 (4.8%) patients presented with paradoxical skin manifestation of whom 8 (57.1%) had previously experienced paradoxical skin manifestation associated with anti-TNF therapy. Among the 173 patients with Crohn's disease, 35 (20.2%) presented with active perianal disease at baseline including 30 (17.3%) with perianal fistula and 5 (2.9%) with perianal fissure. At week 14, complete remission of perianal Crohn's disease was observed in 15 (42.9%) of patients whereas partial remission was observed in 2 (5.7%) patients. At week 54, 12 (34.3%) patients were still in complete remission whereas 12 discontinued VDZ therapy and 13 had no response. Additionally, three patients presented with perianal disease during the follow-up period despite VDZ therapy. Conclusion : VDZ therapy was effective for achieving complete resolution of EIM in patients with IBD in approximately half of the cases. VDZ was also effective for perianal CD in one third of the patients. Paradoxical skin manifestation may occur upon VDZ therapy suggesting as a class effect not restricted to anti-TNF agents.

Sa1930 Sa1928 DISCONTINUATION OF CORTICOSTEROIDS AMONG ULCERATIVE COLITIS PATIENTS TREATED WITH VEDOLIZUMAB IN THE UNITED STATES (US) Haridarshan Patel, Benjamin Chastek, Kyle D. Null, Dirk Demuth

THERE IS NO DIFFERENCE IN SHORT-TERM COLECTOMY RATE BETWEEN INFLIXIMAB-EXPOSED AND INFLIXIMAB-NAÏVE HOSPITALIZED ULCERATIVE COLITIS PATIENTS Sanchit Gupta, Shailja Shah, Steven Naymagon, Hinaben J. Panchal, Bruce E. Sands, Benjamin L. Cohen, Marla Dubinsky

Introduction Corticosteroids (CS) are effective in the short-term induction of patients with moderate to severe ulcerative colitis (UC) but not for maintenance of remission, due to the associated risks. Vedolizumab (VDZ), a humanized monoclonal anti-α4β7 integrin antibody, is approved for the treatment of adults with moderately-to-severely active UC. This study assessed VDZ treatment persistence and CS discontinuation among UC patients co-induced with CS. Methods Adult (≥18 years) CD patients initiating VDZ between 1 May 2014 and 30 September 2016 were identified in the US Optum Research Database. Patients with ≥12 months history (baseline) before their first VDZ claim (index date) and who completed induction (defined as ≥3 infusions in ≥98 days post-index) were included. CS-related measures included: dependence (≥80% CS use during the 6 months immediately prior to index date), co-induction with CS (CS fill for ≥28 days during the induction phase), CS discontinuation (treatment gap ≥60 days between CS fills) while on VDZ therapy. VDZ persistence was defined as no treatment gap ≥90 days between consecutive infusions. CS discontinuation and VDZ persistence were measured using the Kaplan-Meier method. Results A total of 151 VDZ patients were included with a mean (SD) age of 42.8 (16.6) years; 41% female, median follow-up period of 251 days. During baseline, 81%, 45% and 90% of patients were treated with aminosalicylates, immunomodulators, and CS, respectively; 68% of patients had received a biologic before initiating VDZ. Of UC VDZ patients, 52% (n=79) were co-induced with CS during the induction phase, of whom, 18% (14/79) were CSdependent. Overall, 57% (45/79) of CS co-induced patients discontinued their CS and among CS-dependent patients, 36% (5/14) discontinued their CS. CS discontinuation and VDZ persistence are shown in Figures 1a & 1b. Conclusion This real-world study, using a nationally representative US database, showed that nearly half of UC patients receiving VDZ were not co-induced with CS. Among VDZ patients co-induced with CS, over half discontinued during the follow-up period. Despite the treatment-refractory patients included in this study, the CS discontinuation rate at 26 weeks among VDZ patients was higher than what was reported from the GEMINI clinical trials. VDZ persistence was similar between CS co-induced patients versus those without CS co-induction. Future studies should examine CS-related outcomes over a longer follow-up period.

Background: Approximately 15-20% of ulcerative colitis (UC) patients will have a severe attack warranting hospitalization, with 20% potentially requiring colectomy. Although infliximab (IFX) is now common practice in the management of hospitalized UC patients, inpatient dosing is based on the landmark ACT 1 & 2 trials, which were performed in outpatients and specifically excluded hospitalized patients and patients with prior IFX exposure. We aimed to examine outcomes among acute hospitalized UC patients with and without prior IFX exposure. Methods: This was a retrospective study of UC patients admitted to Mount Sinai Hospital from January 2011-April 2016. Inclusion criteria were: UC diagnosis confirmed prior to admission based on standard criteria; hospitalization for acute UC; and at least one rescue dose of IFX given during hospitalization. Primary outcome was 30-day colectomy rate. Statistical analyses were done in Stata. Results: A total of 23 IFX-exposed and 146 IFX-naïve patients were included. IFX-exposed patients had significantly longer disease duration compared to IFX-naïve patients (78 vs. 24 months, p=0.005); otherwise, both had similar key demographic, clinical, and laboratory parameters including age (28 vs. 33 years), sex, BMI, oral steroids prior to admission (68.2% vs. 74.7%), pancolitis (68.2% vs. 72.7%), at least Mayo 2 endoscopic disease (95% vs. 98.6%), c. difficile positivity (13.6% vs. 10.7%), albumin nadir (2.7 vs. 2.8 g/dL), CRP peak (57 vs. 52 mg/dL), and hemoglobin nadir (9.1 vs. 9.3 g/dL) prior to IFX infusion (p=NS). IFX-exposed patients were more likely to have prior exposure to a non-IFX anti-TNFa agent (p<0.001) and were more likely to be initiated on high-dose IFX (10 mg/kg) instead of standard 5mg/kg at hospitalization compared to IFX-naïve patients (56.5% vs. 17.8%; p<0.001). However, there was no difference in primary outcome, 30-day colectomy rate, between IFX-exposed and -naïve patients (17.4% vs. 17.1%, p=0.99). IFX-exposed patients had shorter LOS (6 vs. 8 days, p=0.012), but had 3 more total bowel movements (BMs) at discharge per day (5 vs. 2 BMs/day, p=0.0002), and were more likely to still experience bloody BMs at discharge (93.7% vs. 26.1%, p < 0.001) compared to IFX-naïve patients, respectively. Conclusion: Although IFX-exposed patients hospitalized with acute UC were more likely to receive high-dose IFX compared to IFXnaïve patients and were less likely to respond clinically compared to IFX-naïve patients treated with inpatient IFX, there was no difference in short-term colectomy rates between the groups. Further study focused on IFX dose optimization in the hospitalized UC population with known higher inflammatory burden and high risk of progression to colectomy is needed.

AGA Abstracts

S-396