BACKGROUND:Patient age can impact the safety and efficacy of ulcerative colitis (UC) treatments. Etrasimod is an oral, once daily (QD), selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active UC. Here, we evaluate the impact of age on etrasimod safety and efficacy in patients with UC in the phase 3 ELEVATE UC clinical program. METHODS:Data were pooled from ELEVATE UC 52 and ELEVATE UC 12 in patients receiving etrasimod 2 mg QD or placebo. Proportions and incidence rates (IRs) per 100 patient-years of treatment-emergent adverse events (AEs) were stratified by age (<40, 40-59, and ≥60 years). With the same age stratifications, efficacy was evaluated in patients with baseline Modified Mayo scores of 5-9 and 4-9 for the primary efficacy endpoint (clinical remission) and secondary efficacy endpoints. RESULTS:Overall, 787 patients were enrolled (<40 years, n = 420 [53.4%]; 40-59 years, n = 276 [35.1%]; and ≥60 years, n = 91 [11.6%]). Arthralgia, fatigue, and hypertension IRs were higher in older patients, irrespective of treatment. Serious AEs and AEs leading to treatment discontinuation were low and consistent across age groups. Significantly more patients receiving etrasimod 2 mg QD vs placebo achieved efficacy endpoints, regardless of age. CONCLUSIONS:The safety profile of etrasimod 2 mg QD in the ELEVATE UC population was consistent across age groups, with no change in the incidence of AEs. Patients receiving etrasimod vs placebo showed significant clinical benefit, regardless of age. CLINICALTRIALS.GOV:NCT03945188; NCT03996369.

BACKGROUND AND AIMS:Carbohydrate sulfotransferase 15 [CHST15] biosynthesizes sulphated matrix glycosaminoglycans and is implicated in intestinal inflammation and fibrosis. Here, we evaluate the efficacy and safety of the double-stranded RNA oligonucleotide GUT-1, a specific blocker of CHST15, as induction therapy in patients with ulcerative colitis [UC].METHODS:In this randomized, double-blind, placebo-controlled, phase 2a study, we enrolled endoscopically active UC patients, refractory to conventional therapy, in five hospital centres across Germany. Patients were randomized 1:1:1 using a block randomized technique to receive a single dosing of 25 nM GUT-1, 250 nM GUT-1, or placebo by endoscopic submucosal injections. The primary outcome measure was improvement of endoscopic lesions at weeks 2 or 4. The secondary outcome measures included clinical and histological responses. Safety was assessed in all patients who received treatment.RESULTS:Twenty-eight patients were screened, 24 were randomized, and 21 were evaluated. Endoscopic improvement at weeks 2 or 4 was achieved by 71.4% in the GUT-1 250 nM, 0% in the GUT-1 25 nM, and 28.6% in the placebo group. Clinical remission was shown by 57.1% in the GUT-1 250 nM, 0% in the GUT-1 25 nM, and 14.3% in the placebo groups. Histological improvement was shown by 42.9% in the GUT-1 250 nM, 0% in the GUT-1 25 nM, and 0% in the placebo groups. GUT-1 250 nM reduced CHST15 expression significantly and suppressed mucosal inflammation and fibrosis. GUT-1 application was well tolerated.CONCLUSION:Single dosing by submucosal injection of GUT-1 repressed CHST15 mucosal expression and may represent a novel induction therapy by modulating tissue remodelling in UC.

BACKGROUND & AIMS: The aim of this study was to evaluate the efficacy of LT-02, a novel modified-release phosphatidylcholine (PC) formulation, for induction and maintenance of remission in patients with mild to moderate ulcerative colitis (UC) and inadequate response to mesalamine. METHODS: LT-02 was evaluated in a multicenter double-blind, randomized, placebo-controlled study comprising a 12-week induction trial (PCG-2), followed by a 48-week maintenance trial (PCG-4). In PCG-2, patients were randomized 1:1:1 to treatment with 0.8 g LT-02 4 times daily (QID), 1.6 g LT-02 twice daily (BID), or placebo, respectively. All patients continued to take a standard dose of oral mesalamine ( >= 2.4 g/day). The primary end point in PCG-2 was deep remission. Patients achieving remission at week 12 were randomly assigned 2:1:1 to 1.6 g LT-02 BID, placebo, or 500 mg mesalamine (3 times daily), respectively, in PCG-4; the primary end point was remission at 48 weeks. RESULTS: PCG-2 was terminated early for futility after a prespecified interim analysis; 466 patients (of 762 planned) were randomized. There was no statistically significant difference in deep remission at week 12 (placebo, 13.5%; LT-02 BID, 14.2%; LT-02 QID, 9.7%). In PCG-4, 150 patients (of approximately 400 planned) were randomized. There was no statistically significant difference in remission rates at week 48 (LT-02 BID, 49.3%; mesalamine, 50.0%; placebo, 43.2%). LT-02 was safe. CONCLUSIONS: Despite prior evidence of beneficial effects of PC in phase 2 trials, our induction study with LT-02 in patients with mild to moderate UC was terminated prematurely for futility. Signals of ef fi cacy in maintenance therapy require con fi rmation in an adequately powered maintenance trial. LT-02 was safe and well-tolerated.

The validity and relevance of histologic disease activity in Crohn's disease (CD) is unclear, owing to disconnects with endoscopic pathology. Here, we explore relationships between endoscopic, histologic, and molecular activity. This post hoc analysis of the Phase 2 FITZROY trial (NCT02048618) assessed baseline and week 10 (W10) inflammation across matched ileal and colonic segments in CD patients receiving filgotinib 200 mg (n = 42) vs placebo (n = 18). Macroscopic and microscopic disease were assessed by Simple Endoscopic Score for CD ulceration subscore (uSES-CD) and Global Histologic Activity Score activity subscore (aGHAS), respectively. Molecular activity was quantified by phosphorylated signal transducer and activator of transcription (pSTAT)1 and pSTAT3 in epithelium and nonepithelium. Segments were classified as "low" or "high" activity; correlations and concordance were calculated. Logistic regression identified W10 outcome predictors. Overall, 300 segments in 60 patients were assessed. Baseline uSES-CD and aGHAS correlations were 0.72 and 0.53 in colon and ileum, respectively. pSTAT levels had poor-to-moderate concordance with uSES-CD (kappa range, 0.11-0.49) but moderate-to-good concordance with aGHAS (0.43-0.77). With filgotinib vs placebo, uSES-CD and aGHAS decreased in significantly more segments with high baseline uSES-CD and aGHAS, and significantly more segments with high baseline pSTAT improved at W10. pSTAT1 was more sensitive to change than uSES-CD and aGHAS. Low baseline pSTAT3 in colon nonepithelium predicted W10 low uSES-CD (P = .044). There was better concordance between histologic and molecular disease activity associated with higher sensitivity to change vs endoscopic severity in ileocolonic CD. Our results suggest histologic activity be included in the assessment of CD inflammatory burden.

Background Interleukin (IL)-36 signaling has been shown to be increased in ulcerative colitis (UC). Spesolimab, a novel humanized monoclonal antibody, targets the IL-36 pathway. Research Design and Methods We report safety, immunogenicity, and efficacy data of intravenous (IV) spesolimab in UC. Study 1: phase II, randomized, placebo-controlled trial (300 mg single dose; 450 mg every 4 weeks [q4w]; or 1,200 mg q4w, three doses). Study 2: phase IIa, randomized, placebo-controlled trial (1,200 mg q4w). Study 3: phase IIa, open-label, single-arm trial (1,200 mg q4w). Studies lasted 12 weeks, with a 12-, 24-, and 16-week safety follow-up, respectively. Results Adverse event (AE) rates were similar for spesolimab and placebo in Studies 1 (N = 98; 64.9%; 65.2%) and 2 (N = 22; 86.7%; 71.4%); all patients in Study 3 (N = 8) experienced AEs. The most frequent investigator-assessed drug-related (spesolimab; placebo) AEs were skin rash (5.4%; 0%) and nasopharyngitis (4.1%; 0%) in Study 1; acne (13.3%; 0%) in Study 2; one patient reported skin rash, nasopharyngitis, headache, and acne in Study 3. Efficacy endpoints were not met. Conclusions Spesolimab was generally well tolerated, with no unexpected safety concerns. The safety data are consistent with studies in other inflammatory diseases.

Background Active-comparator trials are important to inform patient and physician choice. We aimed to evaluate the efficacy and safety of monotherapy with either ustekinumab or adalimumab in biologic-naive patients with moderately to severely active Crohn's disease. Methods We conducted a randomised, double-blind, parallel-group, active-comparator, phase 3b trial (SEAVUE) at 121 hospitals or private practices in 18 countries. We included biologic-naive patients aged 18 years or older with moderately to severely active Crohn's disease and a Crohn's Disease Activity Index (CDAI) score of 220-450, who had not responded to or were intolerant to conventional therapy (or were corticosteroid dependent) and had at least one ulcer of any size at baseline endoscopic evaluation. Eligible patients were randomly assigned (1:1; via an interactive web response system) to receive ustekinumab (approximately 6 mg/kg intravenously on day 0, then 90 mg subcutaneously once every 8 weeks) or adalimumab (160 mg on day 0, 80 mg at 2 weeks, then 40 mg once every 2 weeks, subcutaneously) through week 56. Study treatments were administered as monotherapy and without dose modifications. Patients, investigators, and study site personnel were masked to treatment group assignment. The primary endpoint was the proportion of patients who were in clinical remission (CDAI score <150) at week 52 in the intention-to-treat population (ie, all patients who were randomly assigned to a treatment group). This trial is registered with ClinicalTrials.gov, NCT03464136, and EudraCT, 2017-004209-41. Findings Between June 28, 2018, and Dec 12, 2019, 633 patients were assessed for eligibility and 386 were enrolled and randomly assigned to receive ustekinumab (n=191) or adalimumab (n=195). 29 (15%) of 191 patients in the ustekinumab group and 46 (24%) of 195 in the adalimumab group discontinued study treatment before week 52. There was no significant difference between the ustekinumab and adalimumab groups in the occurrence of the primary endpoint; at week 52, 124 (65%) of 191 patients in the ustekinumab group versus 119 (61%) of 195 in the adalimumab group were in clinical remission (between-group difference 4%, 95% CI -6 to 14; p=0.42). Safety for both groups was consistent with previous reports. Serious infections were reported in four (2%) of 191 patients in the ustekinumab group and five (3%) of 195 in the adalimumab group. No deaths occurred through week 52 of the study. Interpretation Both ustekinumab and adalimumab monotherapies were highly effective in this population of biologicnaive patients, with no difference in the primary outcome between the drugs. Copyright (C) 2022 Elsevier Ltd. All rights reserved.

BACKGROUND & AIMS: A large unmet therapeutic need exists in inflammatory bowel disease (IBD). Inhibition of interleukin (IL)-6 appears to be effective, but the therapeutic benefit of a complete IL6/IL6 receptor (IL6R) blockade is limited by profound immunosuppression. Evidence has emerged that chronic proinflammatory activity of IL6 is mainly mediated by trans-signaling via a complex of IL6 bound to soluble IL6R engaging the gp130 co-receptor without the need for membrane-bound IL6R. We have developed a decoy protein, sgp130Fc, that exclusively blocks IL6 proinflammatory trans-signaling and has shown efficacy in preclinical models of IBD, without signs of immunosuppression. METHODS: We present a 12-week, open-label, prospective phase 2a trial (FUTURE) in 16 patients with active IBD treated with the trans-signaling inhibitor olamkicept (sgp130Fc) to assess the molecular mechanisms, safety, and effectiveness of IL6 trans-signaling blockade in vivo. We performed in-depth molecular profiling at various timepoints before and after therapy induction to identify the mechanism of action of olamkicept. RESULTS: Olamkicept was well tolerated and induced clinical response in 44% and clinical remission in 19% of patients. Clinical effectiveness coincided with target inhibition (reduction of phosphorylated STAT3) and marked transcriptional changes in the inflamed mucosa. An olamkicept-specific transcriptional signature, distinguishable from remission signatures of anti-tumor necrosis factor (infliximab) or anti-integrin (vedolizumab) therapies was identified. CONCLUSIONS: Our data suggest that blockade of IL6 trans-signaling holds great promise for the therapy of IBD and should undergo full clinical development as a new immunoregulatory therapy for IBD. (EudraCT no., Nu 2016-000205-36)

ZusammenfassungDie vollständige und reproduzierbare Erfassung und Dokumentation endoskopischer Befunde ist als Grundlage der Behandlung von Patienten mit chronisch entzündlichen Darmerkrankungen wie Morbus Crohn und Colitis ulcerosa von entscheidender Bedeutung. Diese Befunde sind zum einen Grundlage therapeutischer Entscheidungen und zum anderen ein unverzichtbarer Parameter der Bewertung des Ansprechens auf eine Behandlung. Endoskopische Befunde sollten daher nach standardisierten Kriterien erstellt werden, um eine Vergleichbarkeit der Befunde unterschiedlicher Untersucher wie auch die valide Erfassung von Veränderungen im zeitlichen Verlauf der Erkrankung zu gewährleisten. Vor diesem Hintergrund haben 15 Mitglieder der AG Bildgebung des Kompetenznetzes Darmerkrankungen ein Positionspapier erarbeitet, in dem eine Befundstruktur für die Dokumentation endoskopischer Untersuchungen entworfen wird. Die Empfehlungen adressieren neben den formalen Angaben zu jeder Untersuchung insbesondere eine Vielzahl von Attributen akuter und chronisch entzündlicher mukosaler Veränderungen sowie endoskopisch detektierbarer Komplikationen, die detailliert erläutert und anhand charakteristischer Abbildungen illustriert werden. Zudem werden häufiger verwendete endoskopische Aktivitätsindizes vorgestellt, und ihre Nutzung im klinischen Alltag wird diskutiert.

The complete and reliable documentation of endoscopic findings make up the crucial foundation for the treatment of patients with inflammatory bowel diseases such as Crohn´s disease and ulcerative colitis. These findings are, on the one hand, a prerequisite for therapeutic decisions and, on the other hand, important as a tool for assessing the response to ongoing treatments. Endoscopic reports should, therefore, be recorded according to standardized criteria to ensure that the findings of different endoscopists can be adequately compared and that changes in the course of the disease can be traced back. In consideration of these necessities, fifteen members of the Imaging Working Group of the German Kompetenznetz Darmerkrankungen have created a position paper proposing a structure and specifications for the documentation of endoscopic exams. In addition to the formal report structure, the recommendations address a large number of attributes of acute and chronic inflammatory alterations as well as endoscopically detectable complications, which are explained in detail and illustrated using exemplary images. In addition, more frequently used endoscopic activity indices are presented and their use in everyday clinical practice is discussed.

Abstract Background We studied the efficacy and safety of ustekinumab (UST) vs adalimumab (ADA) through 1 year in biologic-naïve patients (pts) with moderate-to-severe Crohn’s disease. Methods SEAVUE was a multicenter, randomized, blinded, parallel-group, active-controlled study in adults with CD Activity Index (CDAI) scores ≥220/≤450. Biologic-naïve pts failing/intolerant to conventional therapy with any size ulcer on baseline (BL) ileocolonoscopy were eligible. Pts were randomized 1:1 to UST (⁓6mg/kg IV at BL then 90mg SC every 8 weeks [Ws]) or ADA (160/80mg SC at BL/W2, then 40mg SC every 2 Ws) per US-approved regimens (no dose modifications). Primary endpoint was clinical remission at W52 (CDAI <150). Major secondary endpoints were corticosteroid-free remission, clinical response (≥100-point CDAI decrease from BL), remission in pt-reported CDAI components (PRO-2 symptom remission: abdominal pain mean daily score ≤1 and stool frequency mean daily score ≤3), and endoscopic remission (SES-CD score ≤3/0 for pts with BL score=3) at W52 and clinical remission at W16. Results 386 pts were randomized to UST or ADA. BL demographics and disease characteristics were balanced between groups and indicative of pts with early, moderate-to-severe CD (median CD duration, 2.58 years; CDAI, 289.5; SES-CD, 8.0). At W52, 65% of UST-treated and 61% of ADA-treated pts achieved clinical remission (Δ=4.0%; 95% CI, -5.5%, 13.5%; p=0.417). Major secondary endpoints, including endoscopic remission, were similar between groups (Table 1), as were remission rates at assessment points through W52. Some other secondary endpoints showed numerical (not statistical) differences between UST and ADA (Table 1). Key safety events are summarized in Table 2. Among UST-treated and ADA-treated pts, 34.0% and 40.5% had infections, 2.6% and 7.2% had serious adverse events (AEs) of worsening CD, and 6.3% and 11.3% had AEs that led to discontinuation (DC) of study drug, respectively. One ADA-treated pt had active pulmonary TB. Injection-site reactions associated with active treatment occurred in 1.0% of UST-treated and 10.3% of ADA-treated pts. Overall, 15.2% of UST-treated and 23.6% of ADA-treated pts DC before W52. Reasons for DC were primarily lack of efficacy (UST, 2.1% vs ADA, 5.1%), AEs (UST, 5.7% vs ADA, 10.7%), and withdrawal of consent (UST, 5.8% vs ADA, 5.1%). Time to treatment DC was longer with UST vs ADA (post hoc analysis). Conclusion Both UST and ADA were highly effective in this population of biologic-naïve pts. Rates of clinical remission at W52 were not statistically significantly different between treatment groups. DC rates were numerically lower for UST. Safety results were consistent with prior experience for both treatments.

BACKGROUND & AIMS:Etrasimod (APD334) is an oral, selective sphingosine 1-phosphate receptor modulator in development for immune-mediated inflammatory disorders. We assessed the efficacy and safety of etrasimod in patients with moderately to severely active ulcerative colitis (UC). METHODS:In a phase 2, proof-of-concept, double-blind, parallel-group study, adult outpatients with modified Mayo Clinic scores (MCSs) (stool frequency, rectal bleeding, and endoscopy findings) of 4-9, endoscopic subscores of 2 or more, and rectal bleeding subscores of 1 or more were randomly assigned to groups given once-daily etrasimod 1 mg (n = 52), etrasimod 2 mg (n = 50), or placebo (n = 54) for 12 weeks. The study was performed from October 15, 2015, through February 14, 2018, at 87 centers in 17 countries. The primary endpoint was an increase in the mean improvement in modified MCS from baseline to week 12. Secondary endpoints included the proportion of patients with endoscopic improvement (subscores of 1 or less) from baseline to week 12. Exploratory endpoints, including clinical remission, are reported in the article, although the study was statistically powered to draw conclusions only on the primary endpoint. RESULTS:At week 12, the etrasimod 2 mg group met the primary and all secondary endpoints. Etrasimod 2 mg led to a significantly greater increase in mean improvement in modified MCS from baseline than placebo (difference from placebo, 0.99 points; 90% confidence interval, 0.30-1.68; P = .009), and etrasimod 1 mg led to an increase in mean improvement from baseline in modified MCS of 0.43 points more than placebo (90% confidence interval, reduction of 0.24 to increase of 1.11; nominal P = .15). Endoscopic improvement occurred in 41.8% of patients receiving etrasimod 2 mg vs 17.8% receiving placebo (P = .003). Most adverse events were mild to moderate. Three patients had a transient, asymptomatic, low-grade atrioventricular block that resolved spontaneously all patients had evidence of atrioventricular block before etrasimod exposure. CONCLUSIONS:In patients with moderately to severely active ulcerative colitis, etrasimod 2 mg was more effective than placebo in producing clinical and endoscopic improvements. Further clinical development is warranted. Clinicaltrials.gov, Number: NCT02447302.

Background: Real-world data on the effectiveness of anti-TNFs on Crohn's Disease (CD) patients bearing poor prognosis factors (PPF) are scarce.This study primarily aimed to generate real-world evidence on the impact of 'early' versus 'delayed' initiation of adalimumab (ADL) treatment on the 26-week clinical remission rate [defined as Harvey-Bradshaw Index (HBI) ≤4] in CD patients bearing PPF at diagnosis.METHODS: This was a multicenter, retrospective, chart-review study performed in 9 Greek Inflammatory Bowel Disease (IBD) Centers which involved adult patients with moderately to severely active CD (HBI ≥8), who were naïve or experienced to biologic therapy at initiation of ADL and beared at least 3 PPF.PPF included ileal or ileocolonic location, age ≤40 years, active smoking, extensive and deep ulceration, severe rectal and/or perianal disease, and upper gastrointestinal involvement.Patients should have been treated with ADL as per the approved label after it was launched in the Greek market (June 2007) and for at least 12 months prior to enrolment.Patients with CD-related intestinal resection before initiation of ADL were excluded.Patients with CD duration less or more than 24 months prior to initiation of ADL were stratified in the 'early' or 'delayed' cohorts, respectively.Sample size calculation estimated that 164 patients [with a 30:70 allocation ratio between the 'early' and the 'delayed' cohorts] was required to address the primary endpoint.Results: A total of 171 eligible patients (initiated on ADL from 01-Jul-2007 to 08-Feb-2017) were consecutively enrolled in the study between 20-Oct-2017 and 01-Apr-2018; 62 (36.3%) were allocated in the 'early' and 109 (63.7%) in the 'delayed' cohort.A median (IQR) of 3 (3-4) PPF were present in each cohort at diagnosis.Baseline characteristics of the two cohorts are displayed in Table 1.The 26-week HBI remission rates (off-steroids) using the last observation carried forward (LOCF) imputation method were 60.7% (37/61) and 47.2% (50/106) in the 'early' and 'delayed' cohorts, respectively (h=13.5%,one-sided p-value: 0.044).The remission rates in the 'early' and 'delayed' cohorts were 61.2% (30/49) versus 42.4% (25/59) among anti-TNF naïve and 58.3% (7/ 12) versus 53.2% (25/47) among anti-TNF experienced patients (one-sided p-values: 0.023 and 0.374, respectively).Conclusion: In CD patients with PPF at diagnosis, early initiation of ADL, within 2 years of diagnosis, achieves significantly higher remission rate compared with delayed introduction of ADL.This effect is more prominent in biologic-naïve patients.Baseline (ADL onset) characteristics

Introduction: The efficacy and safety of etrasimod, a selective, oral S1P receptor 1, 4, and 5 modulator, was evaluated in patients (pts) with moderate-severe UC. Methods: This randomized, double-blind, parallel-group, 12-week (wk) phase 2 induction study evaluated etrasimod in pts with moderate-severe UC, defined as 3-component Mayo Clinic Score (MCS) of 4-9 with endoscopic subscore ≥2 and rectal bleeding (RB) subscore ≥1. The 3-component MCS (range 0-9) includes RB, stool frequency, and endoscopy. Pts received once-daily etrasimod 1 mg (n=52) or 2 mg (n=50), with no dose titration, or placebo (PBO; n=54). The primary endpoint (EP) was change from baseline (BL) in 3-component MCS at wk 12. Secondary EPs included the proportion of pts with endoscopic remission (≤1 point). Exploratory EPs included the proportion of pts achieving clinical remission and clinical response at wk 12 and change in lymphocyte count (LC). Changes in MCS were assessed by analysis of covariance with treatment as a factor and current oral corticosteroid (CS)use, prior antitumor necrosis factor (TNF)a use, and BL measures as covariates; LC was assessed by mixed-effects model and parameters with proportions of pts by the Mantel-Haenszel method with adjustment for current oral CS and prior anti-TNFa use. Results: Of 156 pts randomized, 90% completed the study. BL characteristics, including age, sex, disease duration, current CS use, prior biologic use, were balanced among groups. At wk 12, dose-dependent improvement occurred with etrasimod in all efficacy measures vs PBO (Table). Etrasimod 2 mg improved change from BL in 3-component MCS vs PBO (difference, 0.99 points; 90% CI, 0.30-1.68; P=0.009) (Figure). More pts receiving etrasimod 2 mg achieved endoscopic improvement (41.8% vs 17.8% for PBO; P=0.003). At wk 12, there was a significant decrease in circulating LCs from BL with etrasimod 1 and 2 mg relative to PBO (37.2% and 57.3%, respectively; P<0.001 for both). Adverse events (AEs) were mostly mild to moderate and similar among groups. More PBO-treated pts (11.1%) had a serious AE (SAE) vs etrasimod-treated pts (2 mg, 0%; 1 mg, 5.8%), reflecting disease worsening. No SAEs related to bradycardia or atrioventricular block were noted. Conclusion: In pts with moderate-severe UC, etrasimod was more effective than PBO in achieving dosedependent improvements in clinical response, clinical remission, and endoscopic appearance. Etrasimod was safe and well tolerated in this short-term study.569_A Figure 1 No Caption available.569_B Figure 2 No Caption available.

1: Sandborn et al. William Sandborn: Abbvie – Consultant, Grant/Research Support, Speaker's Bureau. Akros Pharma – Consultant. Allergan – Consultant. Ambrx Inc. – Consultant. Amgen – Consultant, Grant/Research Support. Ardelyx – Consultant. Arena Pharmaceuticals – Consultant. Atlantic Healthcare Limited – Grant/Research Support. Atlantic Pharmaceuticals – Consultant. Avaxia – Consultant. Biogen – Consultant. Boehringer Ingelheim – Consultant. Bristol Meyers Squibb – Consultant. Celgene – Consultant. Celgene/Receptos – Grant/Research Support. Conatus – Consultant. Cosmo Technologies – Consultant. Escalier Biosciences – Consultant, Stockholder/Ownership Interest (excluding diversified mutual funds). Ferring – Consultant. Ferring Research Institute – Consultant. Forward Pharma – Consultant. Galapagos – Consultant. Genentech – Consultant, Grant/Research Support. Gilead Sciences – Consultant, Grant/Research Support. Immune Pharmaceuticals – Consultant. Index Pharmaceuticals – Consultant. Janssen – Consultant, Grant/Research Support, Speaker's Bureau. Kyowa Hakko Kirin Pharma – Consultant. Lilly – Consultant, Grant/Research Support. MedImmune – Consultant. Mesoblast – Consultant. Miraca Life Sciences – Consultant. Nivalis Therapeutics – Consultant. Novartis – Consultant. Nutrition Science Partners – Consultant. Oppilan Pharma – Consultant, Stockholder/Ownership Interest (excluding diversified mutual funds). Otsuka – Consultant. Palatin – Consultant. Paul Hastings – Consultant. Pfizer – Consultant. Precision IBD – Consultant, Stockholder/Ownership Interest (excluding diversified mutual funds). Progenity – Consultant, Stockholder/Ownership Interest (excluding diversified mutual funds). Prometheus Laboratories – Consultant. Qu Biologics – Consultant. Regeneron – Consultant. Ritter Pharmaceuticals – Consultant, Stockholder/Ownership Interest (excluding diversified mutual funds). Robarts Clinical Trials (owned by the University of Western Ontario) – Consultant. Salix – Consultant. Seattle Genetics – Consultant. Seres Therapeutics – Consultant. Shire – Consultant. Sigmoid Biotechnologies – Consultant. Takeda – Consultant, Grant/Research Support, Speaker's Bureau. Theradiag – Consultant. Theravance – Consultant. Tigenix – Consultant. Tillotts Pharma – Consultant. UCB Pharma – Consultant. Vascular Biogenics – Consultant. Vivelix – Consultant. Laurent Peyrin-Biroulet: AbbVie – Consultant, Grant/Research Support, Lecture Fees . Biogen – Lecture Fees. Boehringer Ingelheim – Consultant. Celgene – Consultant. Genentech – Consultant. GlaxoSmithKline – Consultant. Janssen – Consultant, Lecture Fees. Merck Sharp & Dohme – Consultant, Grant/Research Support, Lecture Fees . Oppilan – Consultant. Pfizer – Consultant, Lecture Fees. Roche – Consultant. Shire – Consultant, Lecture Fees. Takeda – Consultant, Grant/Research Support, Lecture Fees. Theravance – Consultant. TiGenix – Consultant. Luba Trokan: Arena – Employee. Jinkun Zhang: Arena – Employee. Tanja Kühbacher indicated no relevant financial relationships. Michael Chiorean: AbbVie – Speaker's Bureau. Arena – Advisory Committee/Board Member. Janssen – Speaker's Bureau. Medtronic – Speaker's Bureau. Pfizer – Advisory Committee/Board Member, Consultant. Salix – Consultant. Takeda – Grant/Research Support, Speaker's Bureau. Scott Lee: AbbVie Pharmaceuticals – Grant/Research Support. Arena Pharmaceuticals – Grant/Research Support. Atlantic Pharmaceuticals, Ltd. – Grant/Research Support. Celgene Pharmaceuticals, Inc. – Grant/Research Support. Cornerstones Health – Advisory Committee/Board Member, Consultant. Eli Lilly and Company – Advisory Committee/Board Member, Consultant. Janssen Pharmaceuticals, Inc. – Advisory Committee/Board Member, Consultant, Grant/Research Support. Pfizer Pharmaceuticals – Advisory Committee/Board Member, Consultant. Salix Pharmaceuticals – Grant/Research Support. Shield Therapeutics PLC – Grant/Research Support. Takeda Pharmaceuticals, Inc. – Grant/Research Support. Tetherex Pharmaceuticals – Grant/Research Support. UCB Pharma – Advisory Committee/Board Member, Consultant, Grant/Research Support. Severine Vermeire: Abbvie – Consultant, Grant/Research Support. Biogen – Consultant. Celgene – Consultant. Ferring Pharmaceuticals – Consultant. Galagapos – Consultant. Gilead – Consultant. Hospira – Consultant. Janssen – Consultant, Grant/Research Support. Merck – Grant/Research Support. Pfizer – Consultant, Grant/Research Support. Second Genome – Consultant. Takeda – Consultant, Grant/Research Support. Bruce Yacyshyn: Merck – Grant/Research Support. Snehal Naik: Arena – Employee. Preston Klassen: Arena – Employee. Julian Panes: AbbVie – Consultant, Grant/Research Support, Lecture Fees. Biogen – Lecture Fees. Boehringer Ingelheim – Consultant. Celgene – Consultant. Genentech – Consultant. Janssen – Consultant, Lecture Fees. Merck Sharp & Dohme – Consultant, Grant/Research Support, Lecture Fees. Oppilan – Consultant. Pfizer – Consultant, Lecture Fees. Roche – Consultant. Shire – Consultant, Lecture Fees. Takeda – Consultant, Lecture Fees. Theravance – Consultant. TiGenix – Consultant. Abstract 2: Sands et al. Bruce E. Sands: Consultant – 4D Pharma, AbbVie, Allergan, Amgen, Arena Pharmaceuticals, Boehringer-Ingelheim, Capella Biosciences, Celltrion Healthcare, EnGene, Ferring, Gilead, Lyndra, Oppilan Pharma, Otsuka, Palatin Technologies, Progenity, Protagonist Therapeutics, Rheos Medicines, Seres Therapeutics, Sienna Biopharmaceuticals, Takeda, Theravance Pharmaceuticals, Vivelix Pharmaceuticals. Advisory Committee/Board Member – Celgene, Janssen, Lilly, MedImmune, Millennium Pharmaceuticals, Pfizer. Grant/Research Support – Janssen, Takeda. William J. Sandborn: Consultant – Abbvie, Akros Pharma, Allergan, Ambrx Inc., Amgen, Ardelyx, Arena Pharmaceuticals, Atlantic Pharmaceuticals, Avaxia, Biogen, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Conatus, Cosmo Technologies, Escalier Biosciences, Ferring, Ferring Research Institute, Forward Pharma, Galapagos, Genentech, Gilead Sciences, Immune Pharmaceuticals, Index Pharmaceuticals, Janssen, Kyowa Hakko Kirin Pharma, Lilly, Medimmune, Mesoblast, Miraca Life Sciences, Nivalis Therapeutics, Novartis, Nutrition Science Partners, Oppilan Pharma, Otsuka, Palatin, Paul Hastings, Pfizer, Precision IBD, Progenity, Prometheus Laboratories, Qu Biologics, Regeneron, Ritter Pharmaceuticals, Robarts Clinical Trials (owned by Health Academic Research Trust or HART), Salix, Seattle Genetics, Seres Therapeutics, Shire, Sigmoid Biotechnologies, Takeda, Theradiag, Theravance, Tigenix, Tillotts Pharma, UCB Pharma, Vascular Biogenics, Vivelix. Grant/Research Support – Atlantic Healthcare Limited, Amgen, Genentech, Gilead Sciences, Abbvie, Janssen, Takeda, Lilly, Celgene/Receptos. Speakers Bureau – Abbvie, Janssen, Takeda. Stockholder/Ownership Interest (excluding diversified mutual funds) – Escalier Biosciences, Oppilan Pharma, Precision IBD, Progenity, Ritter Pharmaceuticals. Remo Panaccione: Consultant – AbbVie, Allergan, Amgen, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado Biosciences, Eisai Medical Research, Elan, EnGene, Eli Lilly, Ferring, Genentech, Genzyme, Gilead, Given Imaging, GlaxoSmithKline, Human Genome Sciences, Janssen, Merck & Co., Merck Research Laboratories, MerckSerono, Millennium, Novo Nordisk, Pfizer, Procter and Gamble, Prometheus Laboratories, Receptos, Salix, Santarus, Shire Pharmaceuticals, Sigmoid Pharma, Sirtris (a GSK company), Takeda, Therakos, Theradvance, and Tillotts. Advisory Committee/Board Member – Abbvie, Abbott, Allergan, Amgen, Aptalis, AstraZeneca, Baxter, Biogen Idec, Celgene, Eisai, Ferring, Genentech, Janssen, Merck, Shire, Elan, Glaxo-Smith Kline, Hospira, Pfizer, Bristol-Myers Squibb, Takeda, Cubist, Salix. Speakers Bureau – Abbvie, Aptalis, AstraZeneca, Celgene, Ferring, Janssen, Merck, Pfizer, Prometheus, Sandoz, Shire, and Takeda. Grant/Research Support – Abbvie, Ferring, Janssen, Shire, Takeda. Christopher D. O’Brien: Employee – Janssen Research & Development, LLC. Hongyan Zhang: Employee – Janssen Research & Development, LLC. Jewel Johanns: Employee – Janssen Research & Development, LLC. Laurent Peyrin-Biroulet: Advisory Committee/Board Member – Abbvie, Janssen, Msd, Genentech, Takeda, Celltrion, Biogen, Amgen, Pfizer, Lilly, Tillots, Ferring, Arena, Index. Consultant – Abbvie, Janssen, Msd, Genentech, Takeda, Celltrion, Biogen, Amgen, Pfizer, Lilly, Tillots, Ferring, Arena, Index. Grant/Research Support – Pfizer, Abbvie, Takeda, Merck Sharp Dohme. Gert van Assche: Consultant – Janssen Research & Development, LLC. Advisory Committee/Board Member – Janssen Research & Development, LLC. Grant/Research Support – Janssen Research & Development, LLC. Silvio Danese: Speakers Bureau – AbbVie, Allergan, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Hospira, Janssen Johnson & Johnson, Merck, MSD, Takeda, Mundipharma, Pfizer, Sandoz, Tigenix, UCB Pharma, Vifor. Consultant – AbbVie, Allergan, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Hospira, Janssen Johnson & Johnson, Merck, MSD, Takeda, Mundipharma, Pfizer, Sandoz, Tigenix, UCB Pharma, Vifor. Advisory Committee/Board Member – AbbVie, Allergan, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Hospira, Janssen Johnson & Johnson, Merck, MSD, Takeda, Mundipharma, Pfizer, Sandoz, Tigenix, UCB Pharma, Vifor. Stephan Targan: Consultant – Janssen, Precision IBD Inc. (co-founder). Advisory Committee/Board Member – Symbiotix. Maria T. Abreu: Consultant – Prometheus Laboratories, Takeda, UCB, Inc., Pfizer, Janssen, Focus Medical Communications, Eli Lilly Pharmaceuticals, Theravance Biopharma Us, Inc. Advisory Committee/Board Member – Abbvie Laboratories, Celgene Corporation, Shire Pharmaceuticals, Roche Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, AMGEN ABP 710 Biosimilar Infliximab, Allergam Brazikumab, SERES, Nestle Health Science, GILEAD. Spe