Patients with ulcerative colitis (UC) who achieve remission with corticosteroids often relapse after tapering or discontinuation; alternative treatments limiting steroid exposure and UC relapse would be beneficial. It remains uncertain whether patients with corticosteroid-induced remission experience benefit with mesalamine granules (MG), a locally acting aminosalicylate extended-release capsule formulation for maintenance of UC remission in adults.

The effects of preceding endoscopic mucosal resection (EMR) on the efficacy and safety of radiofrequency ablation (RFA) for treatment of nodular Barrett's esophagus (BE) is poorly understood. Prior studies have been limited to case series from individual tertiary care centers. We report the results of a large, multicenter registry. We assessed the effects of preceding EMR on the efficacy and safety of RFA for nodular BE with advanced neoplasia (high-grade dysplasia or intramucosal carcinoma) using the US RFA Registry, a nationwide study of BE patients treated with RFA at 148 institutions. Safety outcomes included stricture, gastrointestinal bleeding, and hospitalization. Efficacy outcomes included complete eradication of intestinal metaplasia (CEIM), complete eradication of dysplasia (CED), and number of RFA treatments needed to achieve CEIM. Analyses comparing patients with EMR before RFA to patients undergoing RFA alone were performed with Student's t-test, Chi-square test, logistic regression, and Kaplan-Meier analysis. Four hundred six patients were treated with EMR before RFA for nodular BE, and 857 patients were treated with RFA only for non-nodular BE. The total complication rates were 8.4% in the EMR-before-RFA group and 7.2% in the RFA-only group (P = 0.48). Rates of stricture, bleeding, and hospitalization were not significantly different between patients treated with EMR before RFA and patients treated with RFA alone. CEIM was achieved in 84% of patients treated with EMR before RFA, and 84% of patients treated with RFA only (P = 0.96). CED was achieved in 94% and 92% of patients in EMR-before-RFA and RFA-only group, respectively (P = 0.17). Durability of eradication did not differ between the groups. EMR-before-RFA for nodular BE with advanced neoplasia is effective and safe. The preceding EMR neither diminished the efficacy nor increased complication rate of RFA treatment compared to patients with advanced neoplasia who had RFA with no preceding EMR. Preceding EMR is not associated with poorer outcomes in RFA.

BACKGROUND & AIMS:Complete eradication of Barrett's esophagus (BE) often requires multiple sessions of radiofrequency ablation (RFA). Little is known about the effects of case volume on the safety and efficacy of RFA or about the presence or contour of learning curves for this procedure. METHODS:We collected data from the US RFA Patient Registry (from 148 institutions) for patients who underwent RFA for BE from July 2007 to July 2011. We analyzed the effects of the number of patients treated by individual endoscopists and individual centers on safety and efficacy outcomes of RFA. Outcomes, including stricture, bleeding, hospitalization, and complete eradication of intestinal metaplasia (CEIM), were assessed using logistic regression. The effects of center and investigator experience on numbers of treatment sessions to achieve CEIM were examined using linear regression. RESULTS:After we controlled for potential confounders, we found that as the experience of endoscopists and centers increased with cases, the numbers of treatment sessions required to achieve CEIM decreased. This relationship persisted after adjusting for patient age, sex, race, length of BE, and presence of pretreatment dysplasia (P < .01). Center experience was not significantly associated with overall rates of CEIM or complete eradication of dysplasia. We did not observe any learning curve with regard to risks of stricture, gastrointestinal bleeding, perforation, or hospitalization (P > .05). CONCLUSIONS:Based on analysis of a large multicenter registry, efficiency of the treatment, as measured by number of sessions needed to achieve CEIM, increased with case volume, indicating a learning curve effect. This trend began to disappear after treatment of approximately 30 patients by the center or individual endoscopist. However, there was no significant association between safety or efficacy outcomes and previous case volume.

Introduction: Endoscopic mucosal resection (EMR) is effective for the removal of nodular neoplastic mucosa in Barrett's esophagus (BE) with high grade dysplasia (HGD). While EMR is commonly performed prior to ablation, the impact of early EMR on the subsequent risk of esophageal adenocarcinoma (EAC) after radiofrequency ablation (RFA) is unknown. We compared outcomes of patients with HGD who had EMR then RFA to patients with HGD who had RFA alone. Methods: The U.S. RFA Registry is a study of RFA for BE at 148 centers. Patients were enrolled from 2007-2011 and followed prospectively until 2014. For inclusion in the current investigation, patients had HGD and were free from EAC at baseline. We compared HGD patients receiving EMR prior to RFA to HGD patients receiving RFA alone using Wilcoxon rank sum test for continuous variables and chi-square testing for categorical variables. Logistic regression models were constructed to assess odds ratios (OR) for EAC. Results: Among 5521 patients in the registry, 974 (18%) had HGD. Of these 974, 237 (24%) underwent EMR prior to RFA. Patients who underwent EMR prior to RFA did not differ from those who got RFA alone on age, race, gender, frequency of complete eradication of intestinal metaplasia (CEIM), or time in study, but did have shorter BE at baseline (4.7 vs 5.3 cm, p = 0.008) (Table). Amongst all patients with HGD, 83 (9%) developed EAC. Patients undergoing EMR prior to RFA were less likely to develop EAC (5% vs 10%, p = 0.03) or invasive EAC (2% vs 5%, p = 0.04). On logistic regression, after controlling for age, race, gender, BE length, and time in study, patients who did not undergo initial EMR had doubled odds of developing EAC (OR 1.9, 95% CI [1.01-3.6]). The impact of EMR on invasive EAC was similar in magnitude but did not reach significance after adjustment for the same factors (OR 2.7, 95% CI [0.94-7.7]). Conclusion: After controlling for multiple potential confounders, patients with HGD who received EMR prior to RFA were less likely to develop EAC than HGD patients treated with RFA alone. Since nodularity within BE is a risk factor for EAC, this finding is counter-intuitive. The performance of EMR may be a marker for closer mucosal inspection, leading to superior outcomes. Alternatively, facilities able to perform EMR may also perform more effective RFA. Facilities not able to perform EMR may be more likely to perform RFA over areas of nodularity. Early EMR appears to have a role in protecting against EAC.Table 1: Patient Characteristics by EMR performed prior to RFA

BACKGROUND & AIMS Radiofrequency ablation (RFA) is commonly used to treat Barrett's esophagus (BE). We assessed the incidence of esophageal adenocarcinoma (EAC) after RFA, factors associated with the development of EAC, and EAC-specific and all-cause mortality. METHODS We collected data for outcomes of patients who underwent RFA for BE from July 2007 through July 2011 from US multicenter RFA Patient Registry. Patients were followed until July 2014. Kaplan-Meier curves of EAC incidence were stratified by baseline histology. Crude EAC incidence and mortality (all-cause and EAC-specific) were calculated, and adjusted all-cause mortality was assessed. Logistic regression models were constructed to assess predictors of EAC and all-cause mortality. RESULTS Among 4982 patients, 100 (2%) developed EAC (7.8/1000 person-years [PY]) and 9 patients (0.2%) died of EAC (0.7/1000 PY) in a mean 2.7 ± 1.6 years. The incidence of EAC in nondysplastic BE was 0.5/1000 PY. Overall, 157 patients (3%) died during follow-up (all-cause mortality, 11.2/1000 PY). On multivariate logistic regression, baseline BE length (odds ratio, 1.1/ cm) and baseline histology (odds ratios, 5.8 and 50.3 for low-grade dysplasia and high-grade dysplasia [HGD] respectively) predicted EAC incidence. Among 9 EAC deaths, 6 (67%) had baseline HGD, and 3 (33%) had baseline intramucosal EAC. The most common causes of death were cardiovascular (15%) and extraesophageal cancers (15%). No deaths were associated with RFA. CONCLUSIONS Based on analysis of a multicenter registry of patients who underwent RFA of BE, less than 1% died from EAC. The incidence of EAC was markedly lower in this study than in other studies of disease progression, with the greatest absolute benefit observed in patients with HGD.

Introduction: AVX-470 is an oral, enteric-coated, bovine-derived, polyclonal antibody designed to target TNF in the GI tract without significant systemic exposure. A double-blind, placebo-controlled, first in-human trial was undertaken to explore the pharmacodynamics (biomarkers, clinical, endoscopic response), pharmacokinetics (tissue, stool, systemic bioavailability), immunogenicity and safety of 4 weeks of AVX-470 administration in patients with active UC. Methods: Patients with active UC, total Mayo score 5-12 and endoscopic subscore ≥2, were randomized to receive one of three doses of AVX-470 (0.2 g/d, 1.6 g/d, 3.5 g/d) or placebo in ascending dose cohorts over 4 weeks. Concomitant 5-ASA, corticosteroids, and immunosuppressive agents, and prior use of a systemic anti-TNF agent with secondary failure, were permitted. Colonoscopy was scored centrally by UCEIS (ulcerative colitis endoscopic index of severity). Bovine Ig penetration and biomarkers were assessed in biopsy tissue. Methods were developed to detect induction of human anti-bovine antibodies (HABA) in serum. Results: Thirty-six patients were enrolled. Fifty percent had pancolitis; 66.7% reported prior or concomitant use of corticosteroids, and 41.7% and 33.3% failed prior immunosuppressive or anti-TNF agents, respectively. Dose-related improvements in serum C-reactive protein (p=0.05) and IL-6 (p=0.02) were observed, commencing at week 4, along with dose-related decreases in tissue TNF and myeloperoxidase protein. Bovine Ig was seen in tissues in all colonic segments, consistent with drug penetration into sites of inflammation. TNF-neutralizing capacity was present in stool, with >60% of stools containing bovine Ig at higher doses. Seven of 25 (28%) evaluable patients across all doses of AVX-470 achieved clinical response compared to 1 of 7 (14.3%) receiving placebo (Table 1). A linear gradient of endoscopic effect was observed, with greatest improvement (-1.5 out of 8, UCEIS) in the proximal colon at 3.5 g/d. Serum concentration of anti-TNF antibody ranged from 1.2-3.0 ng/mL (1,000-fold less than systemic TNF activity). No allergic reactions, opportunistic infections, or AE-related dropouts were reported. There was no induction of HABA.Table 1Conclusion: AVX-470 appeared to be safe and well tolerated, with improvement in clinical and biological markers of disease activity in the absence of immunogenicity or significant systemic exposure. AVX-470 holds promise as an orally-delivered anti-TNF agent. The biomarker response at week 4 suggests that longer treatment duration will optimize response. Disclosure - Barbara S. Fox and Deborah S. Hartman are employees of Avaxia Biologics and own stock or stock option in Avaxia. Sharon Spence and Sally Kennedy are consultants to Avaxia. Dr. Harris is a consultant to Avaxia, Theravance, Rhythm Pharmaceuticals, PATH, Lyric Pharmaceuticals, ZS Pharma, CymaBay Pharma, Biomedical Systems, Neurogastrx, and Symbiomix and owns stock and stock options in Avaxia. S. Vermeire has received financial support for research from Abbott Laboratories, Merck Sharp and Dohme, UCB, and is a consultant for Merck Sharpe and Dohme, Abbott Laboratories, UCB, Ferring, Chiesi, Pfizer, and Shire.

RFA decreases the risk of progression to EAC in patients with dysplastic BE. The characteristics of patients who progress to EAC despite RFA therapy are poorly described. Our aim was to identify risk factors associated with progression to EAC among patients who underwent RFA for BE.

Background: Inflammatory bowel disease (IBD) is a chronic disorder that affects approximately 1.4 million Americans, with an annual cost of $10-18 billion. A uniform approach to patient care, such as utilization of practice guidelines, may be beneficial in reducing morbidity and improving patient outcome. Objective: The aim of this study is to determine if proposed American Gastroenterological Association (AGA) quality of care guidelines can be met at a teaching program gastroenterology clinic and to determine if adherence to guidelines results in improved patient outcome. Methods: We performed a retrospective single center study of patients with IBD. Consecutive patients were identified using pharmacy, pathology, and clinic records. 234 patients were identified as having IBD. Of the 234 patients, 126 were followed in the gastroenterology clinic and included in the analysis; the remaining patients used the VA hospital for medication only. The electronic medical record was reviewed for: adherence to the ten quality improvement measures proposed by the AGA, hospitalizations and surgeries within 3 years. Results: 126 patients with IBD were included, patient characteristics are in Table 1. The AGA guidelines were met as follows: Inflammatory Bowel Disease type (99.2%), disease location (92.8%), and disease activity (96%), screening/ cessation counseling in tobacco abusers (98.8%), use of corticosteroid sparing therapy (97.6%), administration of inpatient veno-thromboembolism prophylaxis (89.5%), Yearly Influenza Vaccination (83%), inpatient testing for Clostridium difficile (74%), hepatitis B status prior to initiation of biologic therapy (73%), assessment of bone loss related to corticosteroid therapy (69%), pneumococcus vaccine administration (65%), testing for latent TB prior to initiation of biologic therapy (65%). Overall; 91 patients (72%) met 80% of the quality care guidelines. During the study period of 3 years, 17 patients were admitted for IBD related illness, 10 for non-IBD related illness and 6 patients underwent surgery. We did not find any correlation between adherence to quality of care indications and reduction in hospitalization or surgery (Table 2). Conclusions: Proposed quality of care guidelines can be met in a majority of patients in clinical practice. Adherence to guidelines did not correlate with improved patient outcomes as measured by hospitalization or surgery. Further work is required in identifying quality care measures that correlate with improvement in patient outcomes. Table 1. Patient Characteristics

Subsquamous intestinal metaplasia (SSIM) is defined as metaplastic columnar tissue found beneath an overlying layer of intact squamous epithelium. SSIM occurs in >25% of those with dysplastic Barrett's esophagus (BE), and in 5% or more of patients following radiofrequency ablation (RFA) for BE. We assessed the predictors of SSIM in a nationwide RFA registry.

The optimum surveillance intervals following complete elimination of intestinal metaplasia (CEIM) by radiofrequency ablation (RFA) for Barrett's esophagus (BE) are unknown, and practices vary between institutions. We used data from a nationwide, multicenter registry of patients treated with RFA to assess surveillance practices in community and academic settings following successful ablation.

BACKGROUND: Certolizumab pegol (CZP) is a PEGylated anti-TNF-α therapy that was effective at inducing fistula closure in a post-hoc analysis of the 26-week open-label induction and double-blind maintenance study in Crohn's disease (CD) (PRECiSE 2 [P2], NCT00152425).OBJECTIVE: We now report 3-year data for maintenance of response and remission in the subpopulation of P2 patients with fistulizing CD who continued to receive open-label CZP (PRECiSE 3 [P3] extension study, NCT00160524).METHODS: Patients enrolled in P2 received open-label induction at Weeks 0, 2, and 4 with subcutaneous CZP 400 mg.Responders (≥100-point reduction from baseline in CD Activity Index [CDAI] at Week 6) were randomized to CZP 400 mg or placebo q4w and assessed at Week 26.Patients who completed P2 and entered P3 received open-label CZP 400 mg q4w.In P3, efficacy measures included Harvey-Bradshaw Index (HBI) response (≥3-point decrease from baseline) and remission (HBI ≤4).This analysis only included patients who had open fistulas at Week 0 of P2.Fistula closure was defined as the absence of drainage on gentle compression in ≥50% of open fistulae at any 2 consecutive post-baseline visits at ≥3 weeks apart during the study.RESULTS: 58 patients in the intention-to-treat population of P2 who responded to CZP induction (13.6% of 425) had open fistulas at baseline: 30 were randomized to placebo and 28 to CZP 400 mg.Of these, 35 patients entered P3 (placebo n=14 and CZP 400 mg n=21 from P2). Fistula closure was observed in 52.4% (11/21) of patients assigned to CZP 400 mg compared with 42.9% (6/14) on placebo in P2.Of those in the active group in P2, response and remission rates were higher in patients with fistula closure than in patients with open fistula, and were maintained through to Week 154 of P3 (Table ).CONCLUSIONS: Carry-over from open-label induction led to some fistula response under placebo during the maintenance phase of P2.Most former placebo patients had closed fistula after switching to open-label CZP 400 mg q4w.Long-term maintenance with CZP 400 mg q4w was efficacious at maintaining clinical response and remission in patients with fistulizing CD.

Background and study aims: The use of radiofrequency ablation (RFA) for complete eradication of Barrett's esophagus has shown promise in trials conducted at predominantly tertiary academic centers; however less is known regarding outcomes in the community. We evaluated the safety and efficacy of RFA for Barrett's esophagus delivered in a community practice setting.Patients and methods: This was a multicenter registry conducted in community-based gastroenterology practices. Patients had confirmed intestinal metaplasia with or without dysplasia on biopsy of a Barrett's esophagus. Intervention was step-wise RFA with follow-up esophageal biopsies. Endpoints were histology-based; complete response was defined as all biopsies at most recent endoscopy negative for intestinal metaplasia (CR-IM) or dysplasia (CR-D). Three cohorts were reported: 1) safety cohort, all patients; 2) efficacy cohort A, patients with at least one biopsy session after initial treatment; 3) efficacy cohort B, patients with at least one biopsy session >= 1 year after initial treatment.Results: The safety cohort included 429 patients (71% men, median age 59 years, median Barrett's segment 3.0 cm). There were no serious adverse events (bleeding, perforation, death), and a stricture occurred after 1.1% of cases (2.1% of patients). In efficacy cohort A (n = 338), CR-IM and CR-D were achieved in 72% and 89% of patients, respectively (median follow-up 9 months). In efficacy cohort B (n = 137), CR-IM and CR-D were achieved in 77% and 100% of patients, respectively (median follow-up 20 months).Conclusions: In this multicenter registry conducted at four community-based practices, the observed safety and efficacy outcomes associated with RFA for Barrett's esophagus are comparable to those previously reported in multicenter trials from predominantly tertiary academic centers.

Mesalamine granules (MG) are the first 5-aminosalicylate (5-ASA) formulation to use an innovative delivery system that combines delayedand extended-release mechanisms to release mesalamine directly in the ileum and colon. Agents with a low pill burden and favorable safety profile are more likely to enhance patient compliance in the long-term maintenance of UC remission. Two similarly designed multicenter, randomized, doubleblind, placebo-controlled, phase 3 trials (RCTs) have individually demonstrated significant efficacy of MG (1.5 g, q. d.) for the long-term maintenance of ulcerative colitis (UC). Additionally, an open-label extension trial (OLT) with new and rollover subjects from the two phase 3 trials was conducted to study the long term safety of MG for maintenance of UC remission. The integrated safety data in the expanded population of subjects who received MG from all three trials are presented here (All MG population). Methods: Data for the All MG analyses (n=557) included subjects who received MG in the two RCTs (n=367) and the OLT. The OLT included 197 MGtreated patients who rolled over from the RCTs; and 190 MG naive patients (83 placebo-treated patients from the RCTs, and 107 new patients) all in UC remission. Results: Of 557 patients included in the analysis, 250 patients were exposed for >1 year and 354 were exposed to MG (1.5 g, q.d.) for >6 months. Incidence of treatment-emergent adverse events (TEAEs) was 69.7% in the All MG group. Majority of TEAEs were mild or moderate in intensity, with a profile similar to that during the 6month RCTs. The notably lower incidence of UC flare observed in the RCTs for MG (10.9%) versus placebo (24.3%) was maintained (10.4%) in the OLT. Other common TEAEs in the All MG group were headache (13.8%), diarrhea (9.7%), nasopharyngitis (8.8%), abdominal pain (7.7%), sinusitis (5.4%), and nausea (5.2%). Incidences of serious adverse events and TEAEs leading to study discontinuation were comparable between the 6-month RCT group and the All MG population in the open label study. Occurrences of renal, hepatic, and pancreatic adverse events in patients in the open-label study were ≤1%. Long term compliance for the once-daily treatment regimen was high: mean compliance was ≥ 95% in each treatment group in the RCT population, and 88% for the All MG population. Conclusions: The favorable safety profile of MG when combined with a high compliance of once-daily dosing may support its dispensation as first-line therapy for long-term maintenance of UC remission.

Purpose: Balsalazide 1.1-g tablets are a new high-potency formulation of the azo-bonded 5 aminosalicylate (5-ASA) prodrug balsalazide for first-line treatment of mildly-to-moderately active ulcerative colitis (UC).Key endpoints for three phase 3, multicenter studies included evaluation of safety and tolerability of balsalazide tablets 6.6 g/d.Methods: The balsalazide tablet program consisted of 2 phase 3 double blind studies and 1 open-label extension study.Adults with mildly-to-moderately active UC were randomized to receive either balsalazide tablets 6.6 g/d (3 tablets twice daily), placebo, or mesalamine 2.4 g/d.Safety evaluations included clinical laboratory assessments, vital sign measurements, and adverse event (AE) documentation.Eligible patients from the 2 randomized studies were offered enrollment in an open-label extension study to receive active treatment.Results: A total of 565 patients received at least 1 dose of balsalazide tablets and had at least one postbaseline safety assessment across the three studies.The mean exposure to balsalazide tablets was 225 days.The incidence of treatment emergent AEs (TEAEs) was 71% for subjects treated with balsalazide in the 3 studies, and the majority of AEs were mild or moderate in intensity.In the double-blind studies, the safety profile of the balsalazide group (n=378) was comparable with the placebo group (n=79) and the mesalamine group (n=198).Headache, the most common TEAE in the studies, occurred more frequently in the placebo (14%) and mesalamine (10%) groups than in the balsalazide (8%) group.Worsening UC was also experienced by a larger proportion of the placebo group (15%) compared with the balsalazide (7%) and mesalamine (2%) groups.Other commonly reported AEs (eg, nausea, abdominal pain, nasopharyngitis, vomiting, urinary tract infection) were comparable across the treatment groups.Treatment-emergent serious AEs occurred more frequently in the placebo group (6%) than in either the balsalazide (3%) or mesalamine (<1%) groups.Withdrawals due to AEs were most often related to worsening UC.One death occurred in a subject diagnosed with metastatic malignant melanoma during the open-label study.The death was judged to be unrelated to study drug.Conclusions: Balsalazide 1.1-g tablets administered as 6.6 g/d (3 tablets twice daily) has a favorable safety profile in these studies.Common TEAEs were typically events frequently seen in UC patients or among the general population.The favorable safety profile of balsalazide tablets combined with a convenient, twice-daily dosing regimen, stands to improve patient adherence to therapy and clinical outcomes in the treatment of UC.

Background: Radiofrequency ablation (RFA) for dysplastic and non-dysplastic Barrett's esophagus (BE) has shown favorable outcomes in several cohort studies, a randomized sham-controlled trial, and a multi-center registry; all predominantly conducted at tertiary centers under controlled circumstances. Less is known about the outcomes of RFA when performed in expert community practices. Aim: Determine the safety and efficacy of RFA for dysplastic and non-dysplastic BE in a community practice setting. Methods: Subjects had BE with biopsy confirming non-dysplastic intestinal metaplasia (IM), low-grade (LGD) or high-grade dysplasia (HGD). RFA was performed every 2-4 months with follow-up biopsy at each endoscopy after RFA and/or upon achieving complete endoscopic eradiation of BE. The primary endpoint is histology-based: complete response for dysplasia (CR-D) and IM (CR-IM), defined as no biopsy showing each respective finding.Three cohorts were considered: Safety (all subjects); Efficacy-A (subjects with any post-RFA biopsy despite some not having completed therapy); 3) Efficacy B (subjects with post-RFA biopsy >1 year post-RFA). Results: In the Safety cohort (429 patients, 788 RFA procedures), there were no serious adverse events. By procedure, there were 9 strictures (1.1%), 4 mild bleeding during RFA (0.5%), 1 mucosal injury during RFA (0.1%), 1 fever (0.1%), 1 hematemesis, no intervention (0.1%).Efficacy-A achieved a CR-D and CR-IM in 89% and 72% of subjects, respectively; median BE 3 cm (IQR 2-4), median follow-up 9 mos (IQR 4-18). Efficacy-B achieved a CR-D and CR-IM in 100% and 77% of subjects, respectively; median BE 3 cm (IQR 2-4), median follow-up 20 mos (IQR 17-26). Conclusion: Published clinical trial data reporting on RFA for BE comes from expert tertiary centers conducting the trials under tightly controlled circumstances. We sought to add to this body of evidence by evaluating the outcomes of RFA in the hands of expert community practitioners. In this large series of patients (n=429), we demonstrated a very favorable safety profile, as well as histology-based efficacy outcomes that are comparable to those from published studies.

Mesalamine granules (MG) are the first 5-aminosalicylate (5-ASA) formulation to use an innovative delivery system that combines delayedand extended-release mechanisms to release mesalamine directly in the ileum and colon. Agents with a low pill burden and favorable safety profile are more likely to enhance patient compliance in the long-term maintenance of UC remission. Two similarly designed multicenter, randomized, doubleblind, placebo-controlled, phase 3 trials (RCTs) have individually demonstrated significant efficacy of MG (1.5 g, q. d.) for the long-term maintenance of ulcerative colitis (UC). Additionally, an open-label extension trial (OLT) with new and rollover subjects from the two phase 3 trials was conducted to study the long term safety of MG for maintenance of UC remission. The integrated safety data in the expanded population of subjects who received MG from all three trials are presented here (All MG population). Methods: Data for the All MG analyses (n=557) included subjects who received MG in the two RCTs (n=367) and the OLT. The OLT included 197 MGtreated patients who rolled over from the RCTs; and 190 MG naive patients (83 placebo-treated patients from the RCTs, and 107 new patients) all in UC remission. Results: Of 557 patients included in the analysis, 250 patients were exposed for >1 year and 354 were exposed to MG (1.5 g, q.d.) for >6 months. Incidence of treatment-emergent adverse events (TEAEs) was 69.7% in the All MG group. Majority of TEAEs were mild or moderate in intensity, with a profile similar to that during the 6month RCTs. The notably lower incidence of UC flare observed in the RCTs for MG (10.9%) versus placebo (24.3%) was maintained (10.4%) in the OLT. Other common TEAEs in the All MG group were headache (13.8%), diarrhea (9.7%), nasopharyngitis (8.8%), abdominal pain (7.7%), sinusitis (5.4%), and nausea (5.2%). Incidences of serious adverse events and TEAEs leading to study discontinuation were comparable between the 6-month RCT group and the All MG population in the open label study. Occurrences of renal, hepatic, and pancreatic adverse events in patients in the open-label study were ≤1%. Long term compliance for the once-daily treatment regimen was high: mean compliance was ≥ 95% in each treatment group in the RCT population, and 88% for the All MG population. Conclusions: The favorable safety profile of MG when combined with a high compliance of once-daily dosing may support its dispensation as first-line therapy for long-term maintenance of UC remission.