Sarah R. Goeppinger

Patient Perceptions of Fecal Microbiota Transplantation for Ulcerative Colitis

Background:Fecal microbiota transplantation (FMT), the delivery of stool from a healthy prescreened donor to an individual with disease, is gaining increasing recognition as a potential treatment for inflammatory bowel diseases. Our objective was to describe patient interest in and social concerns around FMT. Methods:We conducted a survey of adults with ulcerative colitis (UC) seen in outpatient clinic at the University of Chicago IBD Center. All English-speaking patients ≥18 years of age were eligible. Subjects completed a written survey in clinic. Ninety-five participants, median age 39 years, 53% female, were enrolled in the study. Results:Forty-four percent and 49% reported excellent or good/satisfactory medical management of their UC, respectively. Forty-six percent participants were willing to undergo FMT as a treatment of UC, 43% were unsure, and 11% were unwilling to undergo FMT. Subjects who had been hospitalized were more willing to undergo FMT, 54% versus 34%, P = 0.035. Primary concerns included the following: adequate screening for infections (41%), cleanliness (24%), and potential to worsen UC (18%); 21% reported no specific concerns. For donor selection, an equal number of participants (46%) preferred whomever their doctor recommended or family member/spouse. Conclusions:In our center despite reporting satisfactory to excellent disease control with their treatments, the vast majority of patients with UC are interested in or willing to consider FMT. Proof of safety and effectiveness, and failure of other medical therapies are key issues in considering FMT. Strong interest in this as-yet unproven therapy warrants attention and is a pressing priority for clinical research and education.

Tu1350 Vedolizumab in the Treatment of IBD: The University of Chicago Experience

G A A b st ra ct s multicentre, observational cohort was designed to examine the safety and efficacy of CTP13 infliximab biosimilar in induction and maintenance of remission in Crohns disease (CD, 108 weeks follow-up) and ulcerative colitis (UC, 54 weeks follow-up). Demographic data were prospectively collected at inclusion. A harmonized, tight monitoring strategy is applied in terms of clinical scores (CDAI, PDAI, pMAYO at each visit), biochemical markers (including CRP, at least every 3 months) and endoscopic/imaging (at least every 12 months) as requested by the National Health Fund. Sera are collected for drug through and antibody measurement at 0, 12, 24 and 52 weeks. Safety data are meticulously registered during follow-up. Results: 90 consecutive IBD patients were included in the present cohort (57 CD patients (27 males) and 33 UC patients (16 males)). Age at disease onset was 26.0 (SD:10.9) years in CD and 30.5 (SD:14.1) years in UC. In CD ileocolonic and perianal disease was present in 40.4% and 37.5% of patients, respectively. 55.2% of UC patients had extensive colitis. 21.4% of CD patients had previous surgery. In CD and UC, 60.4%/ 50% and 55.2%/74.2% of patients received concomitant immunosuppressives and steroids, while 30.4% of CD and 16.1% of UC patients received previous anti-TNFs. At induction, mean CDAI was 289 (SD:107), while MAYO/pMAYO scores were 8.8 (SD 3.1) and 6.4 (SD 2.6) in UC. There was a significant decrease in CDAI after 2 and 6 weeks of treatment compared to baseline (p<0.001, ANOVA-Scheffe). In addition there was a numeric decrease in the mean CRP level (from 23.5mg/L to W2:11.3mg/L and W6:15.3mg/L). There was a significant decrease also in the mean pMAYO score (from 6.4 to (n=16) W2: 3.7 and W6: 3.6) with a numeric decrease in CRP level during induction therapy in UC . 4 allergic reactions occurred, all in patients who had received previous anti-TNF medication. Conclusions: This is the first prospective nationwide cohort examining the safety and efficacy of the biosimilar infliximab in IBD. A significant decrease of disease activity (CDAI and pMAYO) was observed coupled with a decrease in CRP levels during induction with the infliximab biosimilar. A complete analysis of the induction data will be available at the time of congress.

Sa1213 Assessment of the Degree of Variation of Histologic Inflammation in Ulcerative Colitis

Introduction: Treatment goals in ulcerative colitis (UC) are evolving to more objective measures of mucosal inflammation. This has included endoscopic measures, and more recently, histologic measures. However, adoption of histologic endpoints of mucosal healing is hindered by a lack of evidence guiding interpretation and reproducibility of results. Aim: To characterize intra-segment and inter-segment variation of histologic scores of colonic mucosal inflammation in patients with UC. Methods: We analyzed 1802 biopsy fragments from standard of care colonoscopies in 94 UC patients (88 with pancolitis). The biopsies were scored using a novel, previously validated 6-point histologic inflammatory activity (HIA) scale . Location of the biopsies was described as rectum, left, or right side of colon. Biopsies from unlabeled locations were excluded. Variability was determined using both ordinal and continuous representations of HIA scores. In the ordinal intra-segment analysis, the most frequently observed score and the percentage of biopsies with that score were determined for each segment in a colonoscopy. The ordinal inter-segment analysis also calculated the most frequently observed score and the percentage of biopsies with that score but from across all 3 segments. Mean percentages and 95% confidence intervals were then calculated. The continuous analysis used random or fixed effects regression models in order to determine coefficients of variation (COV = standard deviation/mean HIA score). Results: The HIA scores included in the analyses are shown in Table 1. For the ordinal analysis, the mean percentages of intra-segment biopsies with the same HIA score were: 85.5% (95% CI, 80.9-92.9%) for the rectum, 79.6% (CI, 76.0-87.3%) for the left side, and 82.7% (CI, 79.1-90.0%) for the right side. The mean percentage of inter-segment biopsies with the same HIA score was 70.2% (CI, 65.7-82.5%). The continuous inter-segment analysis revealed a COV of 25.4% for HIA scores in patients with left-sided colitis and 14.7% in patients with pancolitis. Neither of these values was significantly greater than zero, the COV expected if all scores were identical (P=0.15 and 0.07, respectively). Both analyses separately revealed that there was no correlation between the degree of inflammation and the degree of intrasegment variation within scores. Conclusions: This is the first study to analyze the variability of histologic inflammation within individual patients with UC. Using our previously validated scoring system, we have demonstrated minimal variability between biopsies within each colonic segment and among different segments. These findings have significant implications for the use of histology as a clinical trial endpoint in UC. 1. Rubin DT, et al. Clin Gastroenterol Hepatol 2013;11:1601-1608. Distribution of HIA Scores

Vedolizumab as Induction and Maintenance for Inflammatory Bowel Disease: 12-month Effectiveness and Safety

Background Vedolizumab is approved for moderate to severe Crohns disease (CD) and ulcerative colitis (UC). We present prospective, 1-year data of the real-world effectiveness and safety of vedolizumab in inflammatory bowel disease. Methods Consecutive patients receiving vedolizumab for treatment of UC or CD with at least 14 weeks of follow-up, regardless of outcome, were included. Patients had clinical activity scores (Harvey-Bradshaw Index [HBI] or Simple Clinical Colitis Activity Index [SCCAI]) and inflammatory markers prospectively measured at baseline and weeks 14, 30, and 52. Clinical response was defined as a reduction ≥3 in HBI or SCCAI, clinical remission as HBI ≤4 or SCCAI ≤2, steroid-free remission as clinical remission without the need for corticosteroids, and mucosal healing (assessed at 6 months) as a Mayo endoscopic subscore of 0 or 1 or CD-SES <3. Results A total of 132 patients were included: 61 (45%) male, 94 (71%) with CD, 42 (29%) with UC; 22% and 34% of CD and UC patients, respectively, achieved steroid-free remission by week 14. This increased to 31% in CD patients and plateaued at 35% in UC patients at 12 months. Increasing remission rates to 6 months were seen in patients with CD, but minimal improvements after 3 months of therapy occurred in those with UC. Mucosal healing was achieved in 52% of UC and 30% of CD patients. Most adverse events were minor; 74% remained on vedolizumab at 12 months. Conclusions In this real-world study, vedolizumab demonstrated similar efficacy and safety seen in pivotal trials, with sustained clinical response in the majority of patients. Similar rates of response were seen in UC and CD patients. 10.1093/ibd/izx067_video1izx067_Video5754037470001.

Safety and Efficacy of Combination Treatment With Calcineurin Inhibitors and Vedolizumab in Patients With Refractory Inflammatory Bowel Disease

Background & Aims Little is known about the efficacy and safety of induction therapy with calcineurin inhibitors in combination with vedolizumab for patients with Crohns disease (CD) or ulcerative colitis (UC). We analyzed the outcomes of patients receiving vedolizumab along with calcineurin inhibitors. Methods We collected data on patients with CD (n = 9) or UC (n = 11) who began treatment with vedolizumab from May 20, 2014, through March 30, 2015, and received calcineurin inhibitors (tacrolimus or cyclosporin) during the first 12 months of vedolizumab therapy. Clinical activity scores and inflammatory markers were measured at baseline and at weeks 14, 30, and 52 of vedolizumab treatment. Clinical remission was defined as a Harvey–Bradshaw index score ≤4 or short clinical colitis activity index score ≤2; steroid‐free clinical remission was defined as clinical remission without corticosteroids. Results By week 14 of treatment, 44% of the patients with CD and 55% of the patients with UC achieved steroid‐free clinical remission; after 52 weeks of treatment, 33% of the patients with CD and 45% of the patients with UC were in steroid‐free clinical remission. Seven patients received salvage therapy with a calcineurin inhibitor after primary nonresponse to vedolizumab—1 of the 2 patients with UC and 2 of 5 patients with CD stopped taking the calcineurin inhibitors and achieved steroid‐free remission at week 52. In total, 16 patients (59%) received 52 weeks of treatment with vedolizumab. Three serious adverse events were associated with calcineurin inhibitors. Conclusions Combination therapy of vedolizumab with either cyclosporin or tacrolimus is effective and safe at inducing and maintaining clinical remission in patients with CD and UC with up to 52 weeks of follow‐up evaluation. Larger studies of the ability of calcineurin inhibitors to induce remission in patients on vedolizumab are warranted.

Fecal Microbiota Transplantation: An Interest in IBD?

Fecal microbiota transplantation (FMT) is a targeted microbiome-based therapy that has garnered a great deal of attention from the scientific, clinical, and lay communities. An increasing number of studies have demonstrated that FMT is a highly effective therapy for recurrent/refractory Clostridium difficile infection and appears safe in the short term. Uncontrolled reports suggest the possibility of benefit in a select group of IBD patients, but there is quite limited information so far. FMT for IBD raises significant issues and concerns that warrant further systematic investigation. In this review, we discuss the background and rationale for this innovative therapy, the current knowledge for FMT in IBD, the logistical issues, and the important issues regarding ethics, social acceptability, and regulation.

Tu1351 Crohn's Disease Patients Currently or Previously on Natalizumab Can Be Safely and Effectively Switched to Vedolizumab

G A A b st ra ct s multicentre, observational cohort was designed to examine the safety and efficacy of CTP13 infliximab biosimilar in induction and maintenance of remission in Crohns disease (CD, 108 weeks follow-up) and ulcerative colitis (UC, 54 weeks follow-up). Demographic data were prospectively collected at inclusion. A harmonized, tight monitoring strategy is applied in terms of clinical scores (CDAI, PDAI, pMAYO at each visit), biochemical markers (including CRP, at least every 3 months) and endoscopic/imaging (at least every 12 months) as requested by the National Health Fund. Sera are collected for drug through and antibody measurement at 0, 12, 24 and 52 weeks. Safety data are meticulously registered during follow-up. Results: 90 consecutive IBD patients were included in the present cohort (57 CD patients (27 males) and 33 UC patients (16 males)). Age at disease onset was 26.0 (SD:10.9) years in CD and 30.5 (SD:14.1) years in UC. In CD ileocolonic and perianal disease was present in 40.4% and 37.5% of patients, respectively. 55.2% of UC patients had extensive colitis. 21.4% of CD patients had previous surgery. In CD and UC, 60.4%/ 50% and 55.2%/74.2% of patients received concomitant immunosuppressives and steroids, while 30.4% of CD and 16.1% of UC patients received previous anti-TNFs. At induction, mean CDAI was 289 (SD:107), while MAYO/pMAYO scores were 8.8 (SD 3.1) and 6.4 (SD 2.6) in UC. There was a significant decrease in CDAI after 2 and 6 weeks of treatment compared to baseline (p<0.001, ANOVA-Scheffe). In addition there was a numeric decrease in the mean CRP level (from 23.5mg/L to W2:11.3mg/L and W6:15.3mg/L). There was a significant decrease also in the mean pMAYO score (from 6.4 to (n=16) W2: 3.7 and W6: 3.6) with a numeric decrease in CRP level during induction therapy in UC . 4 allergic reactions occurred, all in patients who had received previous anti-TNF medication. Conclusions: This is the first prospective nationwide cohort examining the safety and efficacy of the biosimilar infliximab in IBD. A significant decrease of disease activity (CDAI and pMAYO) was observed coupled with a decrease in CRP levels during induction with the infliximab biosimilar. A complete analysis of the induction data will be available at the time of congress.

Tu1349 The Efficacy and Safety of Calcineurin Inhibitors in Inducing and Maintaining Clinical Remission in IBD Patients Commencing Vedolizumab

G A A b st ra ct s multicentre, observational cohort was designed to examine the safety and efficacy of CTP13 infliximab biosimilar in induction and maintenance of remission in Crohns disease (CD, 108 weeks follow-up) and ulcerative colitis (UC, 54 weeks follow-up). Demographic data were prospectively collected at inclusion. A harmonized, tight monitoring strategy is applied in terms of clinical scores (CDAI, PDAI, pMAYO at each visit), biochemical markers (including CRP, at least every 3 months) and endoscopic/imaging (at least every 12 months) as requested by the National Health Fund. Sera are collected for drug through and antibody measurement at 0, 12, 24 and 52 weeks. Safety data are meticulously registered during follow-up. Results: 90 consecutive IBD patients were included in the present cohort (57 CD patients (27 males) and 33 UC patients (16 males)). Age at disease onset was 26.0 (SD:10.9) years in CD and 30.5 (SD:14.1) years in UC. In CD ileocolonic and perianal disease was present in 40.4% and 37.5% of patients, respectively. 55.2% of UC patients had extensive colitis. 21.4% of CD patients had previous surgery. In CD and UC, 60.4%/ 50% and 55.2%/74.2% of patients received concomitant immunosuppressives and steroids, while 30.4% of CD and 16.1% of UC patients received previous anti-TNFs. At induction, mean CDAI was 289 (SD:107), while MAYO/pMAYO scores were 8.8 (SD 3.1) and 6.4 (SD 2.6) in UC. There was a significant decrease in CDAI after 2 and 6 weeks of treatment compared to baseline (p<0.001, ANOVA-Scheffe). In addition there was a numeric decrease in the mean CRP level (from 23.5mg/L to W2:11.3mg/L and W6:15.3mg/L). There was a significant decrease also in the mean pMAYO score (from 6.4 to (n=16) W2: 3.7 and W6: 3.6) with a numeric decrease in CRP level during induction therapy in UC . 4 allergic reactions occurred, all in patients who had received previous anti-TNF medication. Conclusions: This is the first prospective nationwide cohort examining the safety and efficacy of the biosimilar infliximab in IBD. A significant decrease of disease activity (CDAI and pMAYO) was observed coupled with a decrease in CRP levels during induction with the infliximab biosimilar. A complete analysis of the induction data will be available at the time of congress.

The Importance of Mucosal Healing in Ulcerative Colitis

Ulcerative colitis (UC) is an idiopathic condition of the colon, in which acute and chronic inflammation results in an injured bowel. Chronic inflammatory damage, confined exclusively to the mucosa of the colorectum, is the hallmark of the disease. The inflammation is characteristically superficial in nature and appears to begin in the rectum with variable extension to more proximal portions of the colon. This inflammation, and subsequent loss of function, is the mechanism underlying the typical symptoms of UC. Although there may be more systemic symptoms, the majority of the symptoms of UC are derived from an inflamed rectum and due to loss of compliance of the rectum, loss of sensation of stool, as well as symptoms of tenesmus incomplete evacuation, urgency, and bleeding with hematochezia. The healed bowel can result in the resolution of symptoms and has been associated with disease control and resolution, but traditional clinical assessment of UC involves symptom management primarily, with the assumption that when bleeding and urgency are improved, adequate disease control has been achieved. However, resolution of bowel inflammation is not always manifest as improved or resolved symptoms, and improved symptoms are not always associated with a healed bowel or durable disease control. This chapter reviews the importance of mucosal healing as a prognostic marker and therapeutic endpoint in UC.

P-134 Assessment of Health Insurance Access and Financial Hardship of the IBD Population in the US

BACKGROUND: Individuals with chronic health conditions have a more difficult time obtaining health coverage and incur higher medically associated costs. Inflammatory bowel diseases (IBD) are chronic and incurable conditions, yet the impact it has on patients’ ability to obtain health insurance is not known. We sought to assess the obstacles to health insurance coverage for IBD patients and compare these patients to the general population in the U.S. METHODS: We developed the 76-item Crohn’s & Colitis Foundation of American (CCFA) Access to Care Survey (ACS) based in part on the CDC National Health Interview Survey (NHIS)1. The NHIS survey had been previously completed by 34,525 persons 18 years of age and older regardless of race, sex, income, and medical history, and these data are publically available. The ACS was sent electronically to the CCFA global database of 457,037 people, which included the 6548 lay members of the CCFA. A link to the ACS was also advertised on the CCFA’s website and Facebook™ page. Only patients were asked to complete the survey. In this analysis, we analyzed the results related to the purchase of health insurance and compared them to the NHIS results for similar questions. RESULTS: At the time of this survey 3,802 IBD patients or parents of patients completed the ACS, and of these, 13.6% indicated that in the last 12 months they had attempted to purchase private health insurance other than through any employer, union, or government program. Fifty-four percent of these individuals reported being rejected, with 53% reporting higher premiums for available policies. In contrast, 8% of the NHIS participants reported trying to purchase private health insurance in the year preceding that survey, with 8.5% reporting rejection and 13.6% describing higher premiums. In a separate set of questions, 52% of ACS participants indicated there was a time that they could not afford their medication. In contrast, only 8.8% of NHIS participants identified the same problem. Thirty percent and 5.4% of ACS and NHIS participants, respectively, said they did not see a medical specialist due to cost, while 22.3% and 4.9% of ACS and NHIS participants, respectively, did not go to recommended follow-up visits. When analyzing other healthcare needs, 51% and 36.9% of ACS participants did not receive dental care or eyeglasses, respectively, compared to 13.8% and 8.3% of NHIS participants. CONCLUSIONS: This is the first assessment of the insurance and financial burdens that IBD patients face in the U.S. Patients with IBD report a more difficult time finding health care insurance and are charged higher premiums compared to the general population. We also identified additional cost-related limitations to IBD care, including lack of follow-up and inability to obtain medications and other clinical care. The impact of the Affordable Care Act and other novel CCFA initiatives on these findings will be critically important.