Search

Background and Aims: Treating ulcerative colitis (UC) in patients with prior advanced therapy (AT) exposure may be challenging. We report the efficacy and safety of risankizumab, a monoclonal interleukin 23p19 antibody, in patients with UC and prior inadequate response or intolerance to AT (AT-IR)., Methods: In the 12-week phase 3 INSPIRE induction study, patients were randomized to intravenous risankizumab 1200 mg or placebo. Clinical responders were randomized to subcutaneous risankizumab 180 mg, risankizumab 360 mg, or placebo (risankizumab withdrawal) in the 52-week phase 3 COMMAND maintenance study. This post hoc analysis assessed outcomes by AT-IR status, number, and mechanism of action. AT included biologics, Janus kinase inhibitors, and sphingosine-1-phosphate receptor modulators., Results: Efficacy analyses included 472 non-AT-IR and 503 AT-IR patients (induction), and 137 non-AT-IR and 411 AT-IR patients (maintenance). More patients achieved clinical remission per Adapted Mayo score with risankizumab 1200 mg versus placebo at induction week 12 (non-AT-IR, 29.7% versus 8.4%, nominal P < .0001; AT-IR, 11.4% versus 4.3%, nominal P = .0083); consistent with risankizumab 180 mg or risankizumab 360 mg versus placebo (withdrawal) at maintenance week 52 (non-AT-IR, 50.9% or 61.7% versus 31.1%, nominal P = .057 or P = .0033, respectively; AT-IR, 36.6% or 29.5% versus 23.2%, nominal P = .0159 or P = .2334, respectively). Risankizumab had increased efficacy over placebo, regardless of AT-IR number or mechanism of action, with higher efficacy rates for non-AT-IR compared to AT-IR. Safety results in non-AT-IR and AT-IR patients were generally comparable in both induction and maintenance., Conclusions: Risankizumab was effective and well tolerated, regardless of prior AT-IR status., Clinical Trial Registration Numbers: INSPIRE [NCT03398148], COMMAND [NCT03398135]., (© The Author(s) 2025. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background and Aims: Etrasimod is an oral, once daily, selective, sphingosine 1-phosphate [S1P]1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis [UC]. This subgroup analysis evaluated the efficacy and safety of etrasimod 2 mg once daily vs placebo by prior biologic/Janus kinase inhibitor [bio/JAKi] exposure in ELEVATE UC 52 and ELEVATE UC 12., Methods: Pre-defined efficacy endpoints were assessed at Weeks 12 and 52 in ELEVATE UC 52 and Week 12 in ELEVATE UC 12 in bio/JAKi-naïve and -experienced patients, and at Week 12 [pooled] based on prior advanced therapy exposure mechanism., Results: In the ELEVATE UC 52 and ELEVATE UC 12 analysis populations, 80/274 [29.2%] and 74/222 [33.3%] patients receiving etrasimod and 42/135 [31.1%] and 38/112 [33.9%] patients receiving placebo, respectively, were bio/JAKi-experienced. In both bio/JAKi-naïve and -experienced patients, a significantly greater proportion receiving etrasimod vs placebo achieved clinical remission [p < 0.05] in ELEVATE UC 52 at Weeks 12 [naïve: 30.9% vs 9.7%; experienced: 17.5% vs 2.4%] and 52 [naïve: 36.6% vs 7.5%; experienced: 21.3% vs 4.8%]; in ELEVATE UC 12, this was observed only for bio/JAKi-naïve patients [naïve: 27.7% vs 16.2%, p = 0.033; experienced: 18.9% vs 13.2%, p = 0.349]. Similar patterns were observed for most efficacy endpoints. Among patients with prior anti-integrin exposure [N = 90], a significantly greater proportion achieved clinical response [54.1% vs 27.6%, p = 0.030], but not clinical remission [9.8% vs 3.4%, p = 0.248], with etrasimod vs placebo., Conclusions: Bio/JAKi-naïve and -experienced patients had clinically meaningful induction and maintenance treatment benefits with etrasimod vs placebo., Clinicaltrials.gov: NCT03945188; NCT03996369., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). This post hoc analysis reports efficacy and safety by baseline corticosteroid use in the ELEVATE UC clinical programme., Methods: Patients with UC received etrasimod 2 mg or placebo for up to 52 weeks. Corticosteroid use was permitted; tapering was recommended from Week 12. Efficacy was assessed at Weeks 12 and 52 in ELEVATE UC 52, and Week 12 in ELEVATE UC 12, in patients in the corticosteroid (CS) and no-CS subgroups. CS-free efficacy at Week 52 was assessed in patients with baseline CS use., Results: In ELEVATE UC 52 and ELEVATE UC 12, 93/289 (32.2%) and 65/238 (27.3%) patients receiving etrasimod and 42/144 (29.2%) and 34/116 (29.3%) patients receiving placebo, respectively, had concomitant CS use at baseline. In the CS and no-CS subgroups, higher proportions of patients who received etrasimod vs placebo achieved clinical remission (p < 0.05) in ELEVATE UC 52 at Weeks 12 (CS: 32.3% vs 16.7%; no-CS: 26.0% vs 4.9%) and 52 (CS: 31.2% vs 9.5%; no-CS: 33.2% vs 6.9%). In the CS subgroup, significantly more patients receiving etrasimod than placebo achieved CS-free clinical remission at Week 52 (31.2% vs 7.1%). No increases in infection rates were observed with baseline CS use. Safety was comparable between subgroups., Conclusions: Etrasimod demonstrated efficacy in inducing and maintaining remission in both subgroups. CSfree remission was achieved in the CS subgroup. Safety was consistent, with no increase in infections., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background and Aims: Pivotal trials in ulcerative colitis have historically excluded patients with isolated proctitis. Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis. This post hoc analysis assessed efficacy and safety of etrasimod 2 mg once daily in patients with isolated proctitis (centrally read) from the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials., Methods: Patients, including those with isolated proctitis (<10 cm rectal involvement) who met all other inclusion criteria in ELEVATE UC 52 and ELEVATE UC 12, were randomised 2:1 to receive etrasimod or placebo. Primary, secondary and other identified efficacy endpoints and safety were assessed., Results: We analysed data from 64 and 723 patients at Week 12 (both trials pooled), and 36 and 397 patients at Week 52 (ELEVATE UC 52 only) with isolated proctitis and more extensive colitis (≥10 cm rectal involvement), respectively. Patients with isolated proctitis receiving etrasimod demonstrated significant improvements versus placebo, including clinical remission rates at Weeks 12 (42.9% vs 13.6%) and 52 (44.4% vs 11.1%), endoscopic improvement (52.4% vs 22.7%) at Week 12 and bowel urgency numerical rating scale score at Week 12 (all p < 0.01). Generally similar trends were observed in patients with more extensive colitis. Safety was consistent across subgroups, with no new findings., Conclusions: Etrasimod demonstrated significant improvements versus placebo in patients with isolated proctitis, and those with more extensive disease, in most efficacy endpoints at Week 12 and 52. Clinicaltrials.gov: NCT03945188; NCT03996369., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background and Aims: Though colonoscopy plays a crucial role in assessing active ulcerative colitis [aUC], its scope is limited to the mucosal surface. Endoscopic ultrasound [EUS] coupled with contrast-enhancement [dCEUS] can precisely quantify bowel wall thickness and microvascular circulation, potentially enabling the quantitative evaluation of inflammation. We conducted a prospective, longitudinal study to assess therapy response using dCEUS in aUC patients undergoing treatment with adalimumab [ADA] or infliximab [IFX]., Methods: Thirty ADA- and 15 IFX-treated aUC patients were examined at baseline and at 2, 6, and 14 weeks of therapy and 48 weeks of follow-up. Bowel wall thickness [BWT] was measured by EUS in the rectum. Vascularity was quantified by dCEUS using rise time [RT] and time to peak [TTP]. Therapy response was defined after 14 weeks using the Mayo Score., Results: Patients with aUC displayed a mean BWT of 3.9 ± 0.9 mm. In case of response to ADA/IFX a significant reduction in BWT was observed after 2 weeks [p = 0.04], whereas non-responders displayed no significant changes. The TTP was notably accelerated at baseline and significantly normalized by week 2 in responders [p = 0.001], while non-responders exhibited no significant alterations [p = 0.9]. At week 2, the endoscopic Mayo score did not exhibit any changes, thus failing to predict treatment responses., Conclusion: dCEUS enables the early detection of therapy response in patients with aUC, which serves as a predictive marker for long-term clinical success. Therefore, dCEUS serves as a diagnostic tool for assessing the probability of future therapy success., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background and Aims: Colonic epithelial barrier dysfunction is one of the early events in ulcerative colitis (UC) and microRNAs (miRNAs) participate in its regulation. However, cell type-specific miRNome during UC is still unknown. Thus, we aimed to explore miRNA expression patterns in colon tissue and epithelial cells at active and quiescent UC., Methods: Small RNA-sequencing in colon tissue, crypt-bottom (CD44+), and crypt-top (CD66a+) colonic epithelial cells from two cohorts of UC patients (n=74) and healthy individuals (n=50) was performed. Data analysis encompassed differential expression, weighted gene co-expression network, correlation, gene-set enrichment analyses., Results: Differentially expressed colonic tissue miRNAs showed potential involvement in regulation of interleukin-4 and interleukin-13 signalling during UC. As this pathway plays role in intestinal barrier regulation, consecutive analysis of spatially distinct colonic epithelial cell populations was performed. Cell-type (crypt-top and crypt-bottom) specific miRNA expression patterns were identified in both active and quiescent UC. Target genes of differentially expressed epithelial miRNAs at different disease activity were overrepresented in epithelial cell migration and therefore intestinal barrier integrity regulation. The pro-inflammatory miRNA co-expression module M1 correlated with endoscopic disease activity and successfully distinguished active and quiescent UC not only in both epithelial cell populations, but also in the colon tissue. The anti-inflammatory module M2 was specific to crypt-bottom cells and significantly enriched in the quiescent UC patients., Conclusions: miRNA expression was specific to colonic epithelial cell populations and UC state, reflecting endoscopic disease activity. Irrespective of the UC state, deregulated epithelial miRNAs were associated with regulation of intestinal barrier integrity., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background and Aims: Crohn's disease [CD] symptoms are a main driver for impaired quality of life, and fast relief is important for patient care. Stool frequency [SF] and abdominal pain score [APS] are patient-reported outcomes [PROs] measuring symptom severity, which are supported as treatment targets by the STRIDE-II consensus. This post hoc analysis examined the efficacy of risankizumab [RZB], a humanised monoclonal antibody with high specificity for interleukin-23 p19, for providing early symptom relief, along with the prognostic value of early symptom relief for achieving future clinical and endoscopic endpoints., Methods: Individual and combined measures of SF and AP at Weeks 1, 2, and 3 were assessed in patients with moderate to severe CD who received 600 mg intravenous RZB or placebo [PBO] in the ADVANCE or MOTIVATE induction studies. Multivariate logistic regression was used to examine the predictiveness of early symptom improvement for clinical and endoscopic outcomes following RZB induction and maintenance., Results: Higher rates of SF/APS clinical remission and enhanced clinical response were observed as early as Week 1 with RZB vs PBO. A larger proportion of patients achieved clinical endpoints with RZB vs PBO, irrespective of prior bio-failure status. Early PRO improvement was associated with a greater likelihood of achieving clinical and endoscopic improvement following 12-week induction and 52-week maintenance RZB dosing., Conclusions: After the first intravenous RZB induction dose, significantly greater rates of symptom improvement vs PBO were achieved. Improvements could be observed as early as Week 1 and were predictive of Weeks 12 and 52 clinical and endoscopic improvement., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background and Aims: NX-13 activation of NLRX1 reduces intracellular reactive oxygen species and decreases inflammation in animal models of colitis. A phase 1a trial demonstrated a gut-selective pharmacokinetic profile with good tolerability. This phase Ib study aimed to evaluate the safety, tolerability, and pharmacokinetics of NX-13 in patients with active ulcerative colitis [UC]., Methods: We conducted a multicentre, randomized, double-blind, placebo-controlled trial of NX-13 in patients with active UC. Patients with a Mayo Clinic Score of 4-10 were randomly assigned [3:3:3:1 ratio] to three NX-13 oral dose groups (250 mg immediate release [IR], 500 mg IR, or 500 mg delayed release [DR], or placebo) once daily for 4 weeks. Safety and pharmacokinetics were the primary and secondary objectives, respectively., Results: Thirty-eight patients [11 females] were recruited and randomized to placebo [five], NX-13 250 mg IR [11], NX-13 500 mg IR [11], or NX-13 500 mg DR [11] and received at least one dose. There were no serious adverse events or deaths during the trial. One patient [500 mg DR, 1/11] withdrew due to worsening of UC and a second [500 mg IR, 1/11] on the last day of treatment after a panic attack associated with atrial fibrillation. In the efficacy population [36 patients], clinical improvement in rectal bleeding and stool frequency scores relative to placebo were seen as early as week 2 and endoscopic response was seen at week 4., Conclusions: NX-13 was generally safe and well tolerated with early signs of rapid symptom and endoscopic improvement. This novel mechanism of action warrants further investigation. ClinicalTrials.gov: NCT04862741., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background and Aims: Ontamalimab is a fully human immunoglobulin G2 monoclonal antibody against mucosal addressin cell adhesion molecule-1, developed as treatment for inflammatory bowel disease., Methods: Six phase 3, multicentre, randomised, double-blind, placebo-controlled clinical trials compared efficacy and safety of ontamalimab [25 mg and 75 mg once every 4 weeks] with placebo in patients with moderate-to-severe ulcerative colitis or Crohn's disease [two induction studies and one re-randomised maintenance study per condition]. This clinical trial programme was discontinued in 2020 for reasons unrelated to drug safety/efficacy; Crohn's disease studies are described in the Supplementary data., Results: The induction [12-week] and maintenance [52-week] studies included 659 and 366 randomised patients, respectively. More patients who received ontamalimab induction than placebo achieved the primary endpoint of clinical remission at Week 12 [25 mg, 18.5% vs 15.8%, p = 0.617, 27.0% vs 12.5%, p = 0.027; 75 mg, 29.8% vs 15.8%, p = 0.018, 29.5% vs 12.5% p = 0.014]; significantly more patients who received ontamalimab maintenance therapy than placebo achieved Week 52 clinical remission [25 mg, 53.5% vs 8.2%, p <0.001; 75 mg, 40.2% vs 12.8%, p <0.001]. Endoscopic improvement was generally significantly different vs placebo [induction: 25 mg, 27.8% vs 21.1%, p = 0.253, 35.1% vs 12.5%, p = 0.001; 75 mg, 41.1% vs 21.1%, p = 0.002, 33.9% vs 12.5%, p = 0.003; maintenance: 25 mg, 56.3% vs 9.6%, p <0.001; 75 mg, 48.8% vs 15.1%, p <0.001]. Adverse event rates were similar between ontamalimab and placebo groups., Conclusions: Ontamalimab 75 mg was effective, with no safety concerns, as induction and maintenance therapy for patients with moderate-to-severe ulcerative colitis. [NCT03259334; NCT03259308; NCT03290781; NCT03559517; NCT03566823; NCT03627091]., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background and Aims: Treatment of ulcerative colitis [UC] requires a patient-centric definition of comprehensive disease control that considers improvements in aspects not typically captured by classical landmark trial endpoints. In an international initiative, we reviewed aspects of UC that affect patients and/or indicate mucosal inflammation, to achieve consensus on which aspects to combine in a definition of comprehensive disease control, using a modified Delphi process., Methods: The Delphi panel comprised 12 gastroenterologists and one patient advocate. Two gastroenterologists were elected as chairs and did not vote. To inform statements, we asked 18 patients and the panel members about their experiences of remission and reviewed published literature. Panel members voted on statements anonymously in three rounds, with a live discussion before Round 3. Consensus was met if ≥67% of the panel agreed. Statements without consensus in Rounds 1 and 2 were revised or discarded after Round 3., Results: The panel agreed to measure individual patient benefit using a definition of comprehensive disease control that combines aspects currently measured in trials [rectal bleeding, stool frequency, disease-related quality of life, endoscopy, histological inflammatory activity, inflammatory biomarkers, and corticosteroid use] with additional patient-reported symptoms [bowel urgency, abdominal pain, extraintestinal manifestations, fatigue, and sleep disturbance]. The panel agreed on scoring systems and thresholds for many aspects., Conclusions: Using a robust methodology, we defined comprehensive disease control in UC. Next, we will combine the measurement and scoring of these aspects into a multicomponent tool and will adopt comprehensive disease control as a treatment target in clinical practice and trials., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

The emergence of advanced therapies [eg, biologics, Janus kinase inhibitors] over the past few decades has revolutionised the treatment of ulcerative colitis. However, the limitations of these therapies leave an unmet need for safer and more effective or convenient treatment options. There is growing interest in the development of novel oral small molecule therapies for the treatment of ulcerative colitis. Ozanimod is an oral small molecule therapy that is approved in the USA, the European Union, and other countries as the first sphingosine 1-phosphate receptor modulator for the treatment of moderately to severely active ulcerative colitis in adults. This review provides guidance for ozanimod use for the treatment of ulcerative colitis, based on the prescribing information, clinical trial and real-world data, and the authors' clinical experiences. This guidance outlines patient characteristics to consider when deciding if ozanimod treatment is suitable and describes how to educate patients on risks and best practices. It also details the nature and frequency of monitoring during treatment, which should be adapted to the individual patient based on pre-existing risk factors and events that possibly occur during treatment. This review also provides insights into the patient characteristics and clinical scenarios best suited for ozanimod treatment, based on its efficacy, safety profile, and risks compared with other therapies., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background and Aims: Patients with inflammatory bowel disease have increased risk of atherosclerotic cardiovascular [CV] disease [ASCVD]. Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis [UC]. We report major adverse CV events [MACE] in the UC OCTAVE programme, stratified by baseline CV risk., Methods: Rates of MACE were analysed by baseline [first tofacitinib exposure] CV risk profile: prior ASCVD, or 10-year ASCVD risk categories [low, borderline, intermediate, high]., Results: Of 1157 patients [2814.4 patient-years of exposure; ≤7.8 years' tofacitinib treatment], 4% had prior ASCVD and 83% had no prior ASCVD and low-borderline baseline 10-year ASCVD risk. Eight [0.7%] patients developed MACE; one had prior ASCVD. Incidence rates [unique patients with events/100 patient-years of exposure; 95% confidence intervals] for MACE were: 0.95 [0.02-5.27] in patients with prior ASCVD; and 1.81 [0.05-10.07], 1.54 [0.42-3.95], 0.00 [0.00-2.85], and 0.09 [0.01-0.32] in patients without prior ASCVD and with high, intermediate, -borderline, and low baseline 10-year ASCVD risk, respectively. For the 5/7 patients with MACE and without prior ASCVD, 10-year ASCVD risk scores were numerically higher [>1%] prior to MACE versus at baseline, primarily due to increasing age., Conclusions: Most patients receiving tofacitinib in the UC OCTAVE programme had low baseline 10-year ASCVD risk. MACE were more frequent in patients with prior ASCVD and higher baseline CV risk. This analysis demonstrates potential associations between baseline CV risk and MACE in patients with UC, suggesting CV risk should be assessed individually in clinical practice., Clinicaltrials.gov: NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background and Aims: Ulcerative colitis [UC] impacts patients' health-related quality of life [HRQoL]. We assessed HRQoL and an exploratory patient-level composite endpoint ('Comprehensive Disease Control' [CDC]) in individuals receiving filgotinib [an oral JAK1 preferential inhibitor] in the SELECTION trial., Methods: In SELECTION [NCT02914522], a double-blind, randomized, placebo-controlled, phase 2b/3 trial, adults with moderately to severely active UC received once-daily filgotinib 200 mg, filgotinib 100 mg or placebo for 11 weeks in Induction Study A [biologic-naïve] or B [biologic-experienced]. Filgotinib responders [week 10 clinical remission/response] were re-randomized to their filgotinib regimen or placebo for the 48-week Maintenance Study. We assessed week 10 and week 58 SF-36, EQ-5D, WPAI and IBDQ scores. Achievement of CDC (patient-level partial Mayo Clinic Score [pMCS] remission [pMCS ≤2, no individual rectal bleeding, stool frequency or physician's global assessment subscore >1], endoscopic improvement [endoscopic subscore ≤1], faecal calprotectin <150 µg/g and IBDQ score ≥170) and its association with HRQoL and histological outcomes were also explored., Results: Analyses included 382 biologic-naïve and 404 biologic-experienced patients. Filgotinib 200 mg induced and maintained improvements vs placebo in SF-36, EQ-5D, WPAI and IBDQ scores, and restored HRQoL by week 10. Proportionally more filgotinib 200 mg- than placebo-treated patients achieved CDC at weeks 10 and 58 [p < 0.01]. CDC was associated with clinically important improvements in HRQoL and histological remission over both periods., Conclusions: Filgotinib 200 mg results in short- and long-term improvements in HRQoL. High-level improvement of HRQoL relates to a stringent composite endpoint suggesting meaningful disease control in a subset of filgotinib-treated individuals.ClinicalTrials.gov identifier: NCT02914522., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Histological disease severity assessment in ulcerative colitis [UC] has become a mainstay in the definition of clinical endpoints ['histological remission'] in clinical trials of UC. Several scores have been established in the microscopic assessment of disease activity, but the Nancy index [NI] stands out as being the histological index with the fewest scoring items. To what extent histological assessment using the NI is affected by interobserver reliability in a real-word setting is poorly understood. We therefore performed a single-centre retrospective analysis of NI assessment in patients with UC., Methods: We retrospectively evaluated the NI in two independent cohorts [total: 1085 biopsies, 547 UC patients] of clinically diagnosed UC patients, who underwent colonoscopy between 2007 and 2020. Cohort #1 consisted of 637 biopsies from 312 patients, while Cohort #2 consisted of 448 biopsies from 235 patients. Two blinded pathologists with different levels of expertise scored all biopsies from each cohort. A consensus conference was held for cases with discrepant scoring results. Finally, an overall consensus scoring was obtained from both cohorts., Results: The interobserver agreement of the NI was substantial after the assessment of 1085 biopsy samples (κ = 0.796 [95% confidence interval, CI: 0.771-0.820]). An improvement of the interobserver agreement was found with increasing numbers of samples evaluated by both observers (Cohort #1: κ = 0.772 [95% CI: 0.739-0.805]; Cohort #2: κ = 0.829 [95% CI: 0.793-0.864]). Interobserver discordance was highest in NI grade 1 [observer 1: n = 128; observer 2: n = 236]. Interobserver discordance was lowest in NI grades 0 [observer 1: n = 504; observer 2: n = 479] and 3 [observer 1: n = 71; observer 2: n = 66]., Conclusion: The NI is an easy-to-use index with high interobserver reliability for assessment of the histological disease activity of UC patients in a real-world setting. While NI grades 0 and 3 had a high level of agreement between observers, NI grade 1 had a poorer level of agreement. This highlights the clinical need to specify histological characteristics leading to NI grade 1., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Inflammatory bowel disease [IBD] is a chronic relapsing disorder of the gastrointestinal tract, which generally manifests as Crohn's disease [CD] or ulcerative colitis [UC]. These subtypes are heterogeneous in terms of disease location and histological features, while sharing common clinical presentation, genetic associations and, thus, common immune regulatory pathways., Methods: Using miRNA and mRNA coupled transcriptome profiling and systems biology approaches, we report a comprehensive analysis of blood transcriptomes from treatment-naïve [n = 110] and treatment-exposed [n = 177] IBD patients as well as symptomatic [n = 65] and healthy controls [n = 95]., Results: Broadly, the peripheral blood transcriptomes of CD and UC patients were similar. However, there was an extensive gene deregulation in the blood of IBD patients, while only a slight deregulation in symptomatic controls, when compared with healthy controls. The deregulated mRNAs and miRNAs are mainly involved in the innate immunity and are especially enriched in neutrophil activation-related pathways. Oxidative phosphorylation and neutrophil activation-related modules were found to be differentially co-expressed among treatment-naïve IBD as compared to healthy controls. In the deregulated neutrophil activation-related co-expression module, IL1B was identified as the central gene. Levels of co-expression among IL1B and chemosensing receptor [CXCR1/2 and FPR1/2] genes were reduced in the blood of IBD patients when compared with healthy controls., Conclusions: Immune dysregulation seen in peripheral blood transcriptomes of treatment-naïve IBD patients is mainly driven by neutrophil activation., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Ulcerative proctitis is a common and often highly symptomatic form of inflammatory bowel disease. We performed a systematic review to assess the efficacy of different therapies in the management of patients with ulcerative proctitis., Methods: We identified randomized controlled trials in adults with ulcerative proctitis treated with oral or topical therapies for induction of response or remission, or prevention of relapse., Results: A total of 32 randomized controlled trials were included [27 induction/2839 participants, five maintenance/334 participants]. Follow-up varied from 3 to 8 weeks for induction, and from 6 to 24 months for maintenance of remission. 5-Aminosalicylic acid [5-ASA] suppository was the most frequently evaluated treatment [14/32, 43.7%], followed by steroid enema [7/32, 21.9%]. Topical 5-ASA demonstrated effectiveness for induction of clinical response or remission and prevention of relapse in several studies. Combined topical steroids and 5-ASA was more effective than topical 5-ASA or topical steroids alone to induce response [100% of patients for combination vs 70% for beclomethasone alone and 76% for 5-ASA alone]. One observational study suggested azathioprine may be effective in patients with ulcerative proctitis. Only two cohort studies evaluated the efficacy of tumour necrosis factor inhibitors in ulcerative proctitis. Small molecules, anti-integrins and anti-interleukin therapies have not been evaluated in isolated ulcerative proctitis., Conclusion: The role of topical 5-ASA as a treatment for ulcerative proctitis has been confirmed in this systematic literature review, for induction and maintenance of remission. Future trials are needed to investigate the efficacy of more recent and upcoming drug classes in patients with ulcerative proctitis., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Increased mortality from respiratory diseases was observed in epidemiological studies of patients with ulcerative colitis [UC] as a potentially underestimated extraintestinal manifestation. We therefore investigated the presence of pulmonary manifestations of inflammatory bowel disease [IBD] and the potential effect of tumour necrosis factor alpha [TNF-α] inhibitors on pulmonary function tests [PFT] in a prospective, longitudinal study., Methods: In all, 92 consecutive patients with IBD (49 Crohn´s disease [CD], 43 UC) and 20 healthy controls were recruited. Fifty patients with IBD were in remission, and 42 had active disease with 22 of these being examined before and 6 weeks after initiating anti-TNF therapy. Pulmonary function tests [PFT] were evaluated using the Medical Research Council [MRC] dyspnoea index and a standardized body plethysmography. IBD activity was assessed using Harvey-Bradshaw index for CD and partial Mayo score for UC. Data are presented as mean ± standard error of the mean [SEM]., Results: Patients with active IBD showed significant reduction of PFT. Forced expiration [Tiffeneau index] values [FEV1%] were significantly reduced in IBD patients with active disease [78.8 ± 1.1] compared with remission [86.1 ± 0.9; p = 0.0002] and with controls [87.3 ± 1.3; p = 0.001]. Treatment with anti-TNF induced a significant relief in obstruction [p = 0.003 for FEV1% in comparison with baseline levels]. The level of pulmonary obstruction significantly correlated with clinical inflammation scores [HBI or Mayo]., Conclusions: Patients: with active IBD present with significant obstructive abnormalities in their PFTs. Obstruction is related to inflammatory activity, with anti-TNF improving PFTs. Pulmonary obstruction and possibly chronic bronchopulmonary inflammation is an overlooked problem in active IBD that is probably obscured by intestinal symptoms., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

The intense competition for resources to combat COVID-19 has greatly reduced access to health care for patients with other diseases. After the disastrous overrun of hospitals through COVID-19 patients in some jurisdictions, availability of resources for 'elective' medical procedures, including care for the chronically ill, has been greatly reduced in many places as a pre-emptive measure before or during the blooming of infection clusters. Pharmaceutical companies have either stopped recruitment or even cancelled ongoing clinical trials in chronic diseases. Pre-emptive triage and its impact on medical ethics is discussed in the framework of care for inflammatory bowel disease., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Patients with ulcerative colitis [UC] require rapid and complete relief of symptoms, particularly stool frequency and rectal bleeding. The aim of this study was to determine time to symptom resolution in patients with UC during induction treatment with multimatrix mesalazine, and the proportion of patients remaining symptom-free and in endoscopic remission after 12 months of maintenance., Methods: A pooled analysis of 5 pivotal clinical trials, including >1300 patients, evaluating multimatrix mesalazine for treatment of mild-to-moderate active UC was conducted. Time to symptom resolution was defined as the period between first drug dosage date and first 3 consecutive days of induction therapy when the patient achieved a score of 0 [normal] on a modified UC Disease Activity Index for stool frequency and/or rectal bleeding., Results: Median [95% confidence interval] time to resolution of stool frequency was 52 (45-not estimable [NE]) days for placebo versus 38 [34-41] days for multimatrix mesalazine [combined dose groups, 2.4 or 4.8 g/day]; time to resolution of rectal bleeding was 35 [20-NE] days for placebo versus 15 [14-17] days for multimatrix mesalazine [combined dose groups]. Among those who achieved resolution of both stool frequency and rectal bleeding during induction, 67.4% maintained symptom scores of 0 at Month 12. No relationship was observed between rapidity of symptom resolution during induction treatment and achievement of endoscopic remission at Month 12., Conclusions: Induction with multimatrix mesalazine provided rapid and prolonged symptom resolution in addition to endoscopic remission at Month 12., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Intestinal inflammation in inflammatory bowel diseases [IBD] is thought to be T cell mediated and therefore dependent on the interaction between the T cell receptor [TCR] and human leukocyte antigen [HLA] proteins expressed on antigen presenting cells. The collection of all TCRs in one individual, known as the TCR repertoire, is characterised by enormous diversity and inter-individual variability. It was shown that healthy monozygotic [MZ] twins are more similar in their TCR repertoire than unrelated individuals. Therefore MZ twins, concordant or discordant for IBD, may be useful to identify disease-related and non-genetic factors in the TCR repertoire which could potentially be used as disease biomarkers., Methods: Employing unique molecular barcoding that can distinguish between polymerase chain reaction [PCR] artefacts and true sequence variation, we performed deep TCRα and TCRβ repertoire profiling of the peripheral blood of 28 MZ twin pairs from Denmark and Germany, 24 of whom were discordant and four concordant for IBD., Results: We observed disease- and smoking-associated traits such as sharing, diversity and abundance of specific clonotypes in the TCR repertoire of IBD patients, and particularly in patients with active disease, compared with their healthy twins., Conclusions: Our findings identified TCR repertoire features specific for smokers and IBD patients, particularly when signs of disease activity were present. These findings are a first step towards the application of TCR repertoire analyses as a valuable tool to characterise inflammatory bowel diseases and to identify potential biomarkers and true disease causes., (© European Crohn’s and Colitis Organisation (ECCO) 2019.)

Background and Aims: Analyses of Crohn's Disease [CD] studies of anti-TNF agents, including adalimumab, have reported higher remission rates among patients with shorter disease duration. To further explore the relationship between disease duration and clinical efficacy, we analysed a larger patient cohort., Methods: Data were pooled from 10 clinical trials in patients with moderately to severely active CD who received treatment with either adalimumab or placebo. Analyses of efficacy using Crohn's Disease Activity Index [CDAI] endpoints [remission, clinical response [CR]-70, CR-100, patient-reported outcome [PRO] remission] or Harvey-Bradshaw Index [HBI] endpoints [remission/response] were conducted for induction and maintenance treatment periods. Logistic regression was used for comparisons between adalimumab and placebo treatment. Cochran-Armitage trend tests were used for comparisons between disease-duration subgroups [<1 year, ≥1-<2 years, 2-≤5 years, and >5 years]., Results: During induction, the proportion of patients achieving CDAI remission was higher in adalimumab- versus placebo-treated patients [p <0.001] and was highest [adalimumab: 45.8%] in the <1 year subgroup compared with longer disease-duration subgroups [≥1-<2 years: 31.0%; 2-≤5 years: 23.1%; >5 years: 23.6%, Cochran-Armitage p = 0.026]. In the majority of maintenance treatment analyses, patients with <1 year disease duration had the highest efficacy responses, with statistically significant differences in remission rates across disease-duration subgroups., Conclusions: This analysis demonstrates that earlier initiation of adalimumab treatment shortly after diagnosis in patients with moderately to severely active CD leads to improved long-term clinical outcomes., (© European Crohn’s and Colitis Organisation (ECCO) 2019.)

Background and Aims: Matrix metalloproteinase-9 [MMP9] is implicated in the pathogenesis of Crohn's disease and may serve as a potential biomarker. A phase 2 trial was conducted to examine the efficacy and safety of the anti-MMP9 antibody andecaliximab [GS-5745] in patients with moderately to severely active Crohn's disease., Methods: Patients were randomized 1:2:2:2 to receive subcutaneous injections of placebo weekly [QW], andecaliximab 150 mg every 2 weeks [Q2W], andecaliximab 150 mg QW, or andecaliximab 300 mg QW.The co-primary study efficacy endpoints were evaluation of a clinical response, defined as liquid or very soft stool frequency and abdominal pain composite [from Patient-Reported Outcome 2] score ≤ 8 at week 8, and an endoscopic response, defined as a ≥ 50% reduction from baseline in the Simple Endoscopic Score for Crohn's Disease, following 8 weeks of treatment., Results: A total of 187 participants were randomized to treatment; 53 participants were randomized to each andecaliximab treatment group and 28 participants were randomized to placebo. Proportions of patients receiving andecaliximab were not different from proportions of patients receiving placebo based on clinical and endoscopic response and Crohn's disease activity index-defined remission at week 8. Rates of adverse events were comparable among the andecaliximab and placebo groups., Conclusions: Eight weeks of induction treatment with 150 mg andecaliximab Q2W, 150 mg andecaliximab QW, or 300 mg andecaliximab QW in patients with Crohn's disease did not induce a clinically meaningful symptomatic or endoscopic response. Andecaliximab was well tolerated., Clinical Trial Registration: ClinicalTrials.gov NCT02405442., (© The Author(s) 2018. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background and Aim: Recent observational studies document that non-adherence to mesalamine therapy during remission is frequent. We aimed to investigate patient impact of patient education using objective assessments of adherence., Methods: A 14-month randomised, prospective clinical trial of adherence to mesalamine was conducted in 248 patients with ulcerative colitis [UC], Colitis Activity Index [CAI] ≤ 9, receiving standard care [n = 122] versus a standardised patient education programme [n = 126]. Primary endpoint was adherence at all visits (5-aminosalicylic acid [5-ASA] urine levels). Secondary endpoints included quality of life (inflammatory bowel disease questionnaise [IBDQ]), disease activity, partial adherence, and self-assessment of adherence., Results: Patient allocation was well balanced. Baseline non-adherence was high in quiescent/mildly active UC [52.4%] without difference between the groups (52.4% of patients in the education group versus 52.5% in the standard care group [p = 0.99]). No difference between the intervention group and standard care was seen in IBDQ, partial adherence, self-assessment of adherence, or therapy satisfaction at all visits. We suggest a model in which individual risks for non-adherence are driven by patients with young age, short disease duration, and low education levels., Conclusions: Non-adherence is frequent in a population with quiescent/mildly active UC. Although more than 25% of the population was not in remission at the various time points, no relationship between disease activity and adherence was seen over the 14-month observation period. Physicians should maximise their efforts to motivate high-risk patients for adherence. Future trials should use objective exposure assessments to examine the impact of continuous education and consultations on the background of individual risks to develop non-adherence., (Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

The role of placebo in clinical trials for drug development in inflammatory bowel disease [IBD] was the topic of a panel discussion held during the 10th Congress of the European Crohn's and Colitis Organisation [ECCO], in Barcelona, Spain, in 2015. Panellists discussed a number of issues around placebo-controlled trials in IBD, noting issues such as difficulties with recruitment, leading to less then representative patient populations in clinical studies. It was noted that, whereas the easiest answer may be to drop placebo, it is much more complicated than that. The relevance of placebo is affected by a number of factors, including the phase of the trial, as well as the nature of the drug. In most cases where placebo has been left out in drug development, it has been for trials involving a new formulation, a new dosing schedule, or a biosimilar, for example. The panel agreed that placebo-controlled trials are of particular importance early in the development programme, perhaps not so much in phase III, although placebo is important for monitoring safety. The current trial paradigm, in which patients remain on a plethora of, likely ineffective and toxic, background medication, was also questioned. The applicability of placebo in the paediatric population was also discussed. The overall consensus from this panel discussion was that placebo is still necessary in clinical trials in inflammatory bowel disease, but there remain questions as to how and when placebo should be used., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: The best care setting for patients with inflammatory bowel disease [IBD] may be in a dedicated unit. Whereas not all gastroenterology units have the same resources to develop dedicated IBD facilities and services, there are steps that can be taken by any unit to optimise patients' access to interdisciplinary expert care. A series of pragmatic recommendations relating to IBD unit optimisation have been developed through discussion among a large panel of international experts., Methods: Suggested recommendations were extracted through systematic search of published evidence and structured requests for expert opinion. Physicians [n = 238] identified as IBD specialists by publications or clinical focus on IBD were invited for discussion and recommendation modification [Barcelona, Spain; 2014]. Final recommendations were voted on by the group. Participants also completed an online survey to evaluate their own experience related to IBD units., Results: A total of 60% of attendees completed the survey, with 15% self-classifying their centre as a dedicated IBD unit. Only half of respondents indicated that they had a defined IBD treatment algorithm in place. Key recommendations included the need to develop a multidisciplinary team covering specifically-defined specialist expertise in IBD, to instil processes that facilitate cross-functional communication and to invest in shared care models of IBD management., Conclusions: Optimising the setup of IBD units will require progressive leadership and willingness to challenge the status quo in order to provide better quality of care for our patients. IBD units are an important step towards harmonising care for IBD across Europe and for establishing standards for disease management programmes., (© European Crohn’s and Colitis Organisation 2015.)

Background and Aims: Inflammatory bowel diseases are part of a wider conglomeration of immune-mediated inflammatory diseases. New management approaches need to be developed as we understand more of the epidemiology and aetiology of inflammatory bowel diseases and medical care becomes more complex., Methods: Selected new tools and approaches for improved management of inflammatory bowel diseases are presented, based on published evidence and clinical experience., Results: Setting quality of care standards that are consistent across different inflammatory bowel disease care settings will be paramount and require collaboration between specialist and non-specialist centres. Alongside this, the value of care will need to be evaluated in terms of maximising outcomes over the entire care cycle for a patient. In moving towards a value-based approach to management, it is important to determine the progression rate of the disease by measuring cumulative bowel damage. As well as understanding the course of disease in individual patients, it is also becoming more feasible to individualise therapy and exploit drug pharmacology to achieve better and more long-term responses. Finally, it is timely to consider formal collaborations between specialists in immune-mediated inflammatory diseases to ensure more cohesive patient care., Conclusions: The potential for improved management of patients with inflammatory bowel diseases continues to increase as we look to understand when and how to intervene in the disease process and how to adopt a collaborative management approach that promotes networking and reduces heterogeneity of care across different care settings., (Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Patients' and physicians' perceptions of ulcerative colitis and its management are important for developing and guiding appropriate therapies. This study explored national differences in patients' and physicians' experiences, expectations, and beliefs about ulcerative colitis., Methods: Structured, cross-sectional, online surveys evaluating various indices were completed by 775 adult patients with ulcerative colitis and 475 physicians actively managing ulcerative colitis patients from France, Germany, Ireland, Spain, the United Kingdom, and Canada., Results: Patients' classification of their symptom severity differed across countries (mild, 16%-45%; moderate, 46%-58%; severe, 4%-36%). Expectations of disease control also varied, with 26% (Ireland) to 65% (Spain) describing that remission realistically involves "living without symptoms." Within each country, more patients (45%-69%) than physicians (28%-45%) considered ulcerative colitis symptoms to affect patients' quality of life. Mean number of patient-reported flares during the past year ranged from 2.5 in Ireland to 8.0 in France. Self-reported adherence with oral 5-aminosalicylic acid (during remission) was highest in Spain (91% vs 50%-73% across other countries). Spanish patients were more likely to self-adjust their medications (54% vs 2%-5%), but reported the most dissatisfaction with therapy (42% vs 9%-27%). Irish patients were least likely to arrange physician/specialist nurse visits (14% vs 36%-49%) and least open to discussion of their condition., Conclusions: Important national differences in ulcerative colitis patients' attitudes and perceptions were observed, which may help physicians improve patient care based on country-specific needs and influence self-assessments in clinical trials. The results suggest a need for structured patient education to improve adherence and outcomes., (Copyright © 2012 European Crohn's and Colitis Organisation. All rights reserved.)

Background and Aims: We examined the impact of disease duration on clinical outcomes and safety in a post hoc analysis of a remission maintenance trial with adalimumab in patients with moderate to severe CD., Methods: Patients in the CHARM trial were divided into 3 disease duration categories: <2 (n=93), 2 to <5 (n=148), and ≥5 years (n=536). Clinical remission and response rates at weeks 26 and 56 were compared between adalimumab and placebo subgroups, and assessed through 3 years of adalimumab treatment in the ADHERE follow-on trial. Logistic regression assessed the effect of disease duration and other factors on remission and safety., Results: At week 56, clinical remission rates were significantly greater for adalimumab-treated versus placebo-treated patients in all 3 duration subgroups (19% versus 43% for <2 years; P=0.024; 13% versus 30% for 2 to <5 years; P=0.028; 8% versus 28% for ≥5 years, P<0.001). Logistic regression identified shorter duration as a significant predictor for higher remission rate in adalimumab-treated patients. Patients with disease duration <2 years maintained higher remission rates than patients with longer disease duration through 3 years of treatment. The incidence of serious adverse events in adalimumab-treated patients was lowest with disease duration <2 years., Conclusions: Adalimumab was superior to placebo for maintaining clinical remission in patients with moderately to severely active CD after 1 year of treatment regardless of disease duration. Clinical remission rates through 3 years of treatment were highest in the shortest disease duration subgroup in adalimumab-treated patients, with a trend to fewer side effects., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Intestinal barrier function in Crohn's disease patients and their first degree healthy relatives is impaired. The increased intestinal permeability may result in an enhanced mucosal immune response and thereby aggravate intestinal inflammation. Humanised anti-TNF-α antibodies have been shown to be effective in the treatment of active Crohn's disease and in the treatment of entero-cutaneous fistula. The aim of the present study was to investigate the influence of anti-TNF-α antibody (infliximab) treatment on the intestinal barrier function of patients with active Crohn's disease., Methods: The differential intestinal uptake of lactulose and mannitol was measured to quantify intestinal permeability in patients with long standing active Crohn's disease (n=17) directly before and seven days after treatment with infliximab (5 mg/kg bodyweight). In parallel, intestinal permeability was studied in a healthy control group (n=20). Serum samples were analysed with pulsed amperometric detection after separation on an anion exchange column., Results: Intestinal permeability was significantly increased in all patients with Crohn's disease (L/M ratio 0.24±0.17) prior to infliximab treatment compared to the control group (L/M ratio 0.01±0.02; p-value <1×10(-7)). Treatment of patients with infliximab resulted in a marked decrease of intestinal permeability as measured by L/M ratio from 0.24±0.17 before to 0.02±0.02 (p-value <1×10(-7)) seven days after infliximab application., Conclusions: Treatment with anti-TNF-α antibodies improved impaired intestinal barrier function in patients with Crohn's disease. This effect may correlate to the well documented anti-inflammatory effect of TNF-α blockade in this intestinal disease., (Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Introduction: Latent tuberculosis infection is detected by the tuberculin skin test before treating with anti-Tumour-Necrosis factor alpha (anti TNFα) reagents. More accurate are Interferon gamma release assays (IFNγ release assays) to identify patients with latent tuberculosis. Because of a positive control in this assay, it is possible to identify those patients in which a result of tuberculosis testing is not available due to a lack of stimulation capacity of lymphocytes (indeterminate result). Patients suffering from IBD are often treated with immunosuppressive agents, which may influence the results of tuberculosis testing., Aim: The aim is to investigate the influence of immunosuppressive agents on the outcome of IFNγ-release assay., Methods: 50 consecutive patients were documented before introducing anti-TNF-treatment in this single centre study between April 2009 and April 2010. Data of INFγ release assay for latent tuberculosis, skin test and laboratory data and current medication were enrolled., Results: For the period of one year data of 45 consecutive patients was available for statistical analysis. 24 patients out of 45 (corresponding to 53.3%) received at least low doses of corticoid treatment and 27 patients out of 45 (corresponding to 60.0%) received immunosuppressive agents. 13 patients out of 45 (corresponding to 28.9%) had an indeterminate result of the QuantiFERON test. A correlation between the indeterminate result and combination therapy of corticosteroids was found. The concomitant therapy of immunosuppressive agents lead to a lower IFN release but no significance was found., Conclusions: Steroid treatment and further combination therapy with immunosuppressive agents lead to a high risk of indeterminate QuantiFERON test., (Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Infliximab is currently the only biologic approved for treatment of adults with moderate to severe, active ulcerative colitis (UC) unresponsive to conventional therapies. It rapidly controls symptoms, induces and sustains steroid-free remission, stimulates mucosal healing, and reduces serious complications. Although infliximab tends to be reserved for patients with severe disease, it may be even more beneficial for moderate disease earlier in the disease course. Therefore, it is important to identify which patients are candidates for infliximab therapy., Methods: A collaborative Delphi survey was used to obtain consensus on use of biologic therapy in patients with UC from an expert panel of 12 gastroenterologists with substantial experience using infliximab in clinical practice and clinical trials. The panel also addressed issues that influence the use of infliximab in UC, including its potential as an alternative to surgery., Results: The panel agreed that: (1) it is necessary to adopt additional treatment goals beyond symptom control, i.e., complete mucosal healing, steroid-free remission, improved QoL, and reduced long-term complications; (2) it may be possible to achieve these treatment goals with infliximab, especially if it is used earlier in the course of UC; and (3) infliximab should be offered as an alternative to surgery in patients being considered for colectomy. The panel also agreed on factors for identifying candidates for infliximab therapy (e.g., persistently active UC, steroid-dependent/refractory disease, and high C-reactive protein)., Conclusions: This consensus statement provides useful and practical information on how to achieve evolving treatment goals with infliximab in moderate to severe UC., (Copyright © 2011. Published by Elsevier B.V.)

Introduction: Environmental factors may play an important role in the pathogenesis of IBD. The history of patients of the German IBD twin study was analyzed by questionnaires and interviews., Methods: Randomly selected German monozygotic (MZ) and dizygotic (DZ) twins with at least one sibling suffering from IBD (n=512) were characterized in detail including demography, medical history and concomitant medications. Controls comprised of non-twin IBD patients (n=392) and healthy subjects (n=207)., Results: The most significant variables that were associated with Crohn's disease (CD) or ulcerative colitis (UC) included living abroad before time of diagnosis (OR, 4.32; 95% CI, 1.57-13.69), high frequency of antibiotic use (MZ CD OR, 5.03; 95% CI 1.61-17.74, DZ CD OR, 7.66; 95% CI, 3.63-16.82, MZ UC OR, 3.82; 95% CI, 1.45-10.56, DZ UC OR, 3.08; CI, 1.63-5.92), high consumption of processed meat including sausage (MZ CD OR, 7.9; 95% CI, 2.15-38.12, DZ CD OR, 10.75; 95% CI, 4.82-25.55, MZ UC OR, 5.69; 95% CI, 1.89-19.48, DZ UC OR, 18.11; 95% CI, 7.34-50.85), and recall of bacterial gastrointestinal infections (MZ CD OR, 15.9; 95% CI, 4.33-77.14, DZ CD OR, 17.21; 95% CI, 4.47-112.5, MZ UC OR, 5.87; 95% CI, 1.61-28.0, DZ UC OR, 11.34; 95% CI, 4.81-29.67)., Conclusions: This study reinforced the association of life style events, in particular a specific dietary and infections history, with IBD. Alteration of gut flora or alterations of the mucosal immune system in reactivity to the flora could be an important factor to explain the relationship between life-style and disease., (Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

The introduction of anti-tumour necrosis factor therapies has provided highly effective treatments for Crohn's disease, making it possible to significantly improve the prognosis of patients. However, neither conventional non-biological therapies nor anti-tumour necrosis factor therapies are routinely used to optimum effect. There are several reasons for this, including a lack of specific evidence to guide common clinical questions and a lack of clearly defined treatment targets. This paper suggests some simple changes to the management of Crohn's disease that have the potential to significantly improve patient outcomes. A new treatment target, 'deep remission', which includes mucosal healing as well as clinical remission, may be the first step in defining the successful treatment of Crohn's disease; early clinical studies have demonstrated that this is a readily achievable target. Initiating appropriate treatment early can increase clinical remission rates, improve steroid sparing, induce mucosal healing and prevent structural bowel damage, whereby reducing the need for hospitalization and surgery. There are also clear indications that modifying treatment based on regular objective assessments of disease activity to provide tight disease control can improve patient outcomes in a similar way to that observed in rheumatoid arthritis. These simple changes to management strategy appear to allow the full potential of available treatments to be realized. Clinical studies to further define optimized treatment strategies for Crohn's disease are underway and will provide future direction., (Copyright © 2012 European's Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Purpose: A two-allele haplotype of TC (OCTN1 rs1050152 and OCTN2 -207G→C) is associated with Crohn's disease (CD). The association has been replicated in different populations, but also failed in some studies. The present study is to replicate the association of OCTN1 rs1050152 and examine another variant rs272879 with familial and sporadic inflammatory bowel disease (IBD) in a cohort from central Pennsylvania, USA., Methods: The study samples (n=465) included 212 inflammatory bowel disease patients (CD=115, UC=97), including 103 familial (CD=55, UC=46) and 111 sporadic (CD=60, UC=51) IBD, 139 non-IBD family members from a familial IBD registry, and 114 unrelated healthy controls. A total of 12 OCTN1 variants within exonic sequences were examined. Two nonsynonymous SNPs, rs1050152 (L503F) and rs272879 (L395V) were genotyped by a PCR-based RFLP/cRFLP method and statistically analyzed. These samples with an additional 141 unrelated healthy samples were also genotyped for rs1050152 using the SNPlex™ Genotyping System., Results: The OCTN1 rs1050152 is associated with CD (OR=1.745, 95% CI=1.019-2.990, χ²=4.129, p=0.042) and with IBD (OR=1.68, 95% CI=1.052-2.676, χ²=4.732, p=0.030); while the variant rs272879 is not associated with IBD, CD or ulcerative colitis (UC). The distribution of the rs1050152 variant showed a high level of the T allele in male UC (OR=2.585, 95% CI=1.139-5.869, p=0.023) and IBD (OR=2.039, 95% CI=1.024-4.059, p=0.042) patients, and in female CD patients (OR=2.329, 95% CI=1.038-5.226, ρ value=0.039)., Conclusion: The present results replicated the association of the OCTN1 rs1050152 (L503F) variant with CD and IBD overall. A weak gender-specific effect of rs1050152 (L503F) on male UC and female CD was observed., (Copyright © 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Aim: To replicate the association of Nkx2-3 rs10883365 SNP with Crohn's disease in patients from a familial IBD registry from the central Pennsylvania area and study mRNA and protein expression of Nkx2-3 in CD patients., Materials and Methods: We genotyped the Nkx2-3 rs10883365 SNP in 75 CD patients,137 non-CD family members and 118 unrelated healthy controls from EBV-transformed B cell lines of a familial IBD registry in central Pennsylvania. mRNA and protein expression levels of Nkx2-3 were measured by RT-PCR and Western blot, respectively., Results: rs10883365 was found to be associated with CD. A significant difference between the homozygous variant genotype (GG) compared to the wild type sequence (AA) was observed between CD and individuals without IBD, including both non-IBD family members from the familial IBD registry and unrelated healthy controls. However, there was not a significant difference between CD and non-IBD related family members. mRNA and protein expression levels of Nkx2-3 were increased in CD compared with non-CD sibling and healthy controls. A total of 16 sibling pairs were examined, and the mRNA and protein expression levels of Nkx2-3 from 12 of the sibling pairs (75%) were increased in the CD individual compared with the non-CD sibling. mRNA expression levels of Nkx2-3 were increased in diseased tissues compared with adjacent normal tissues in 7 of 9 patients (77.8%)., Conclusions: Nkx2-3 is genetically associated with CD and is up-regulated in CD, suggesting that Nkx2-3 is involved in the pathogenesis of CD.