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Background and aims: Current endoscopic activity scores for ulcerative colitis (UC) do not take into account the extent of mucosal inflammation. We have developed a simple endoscopic index for UC that takes into account the severity and distribution of mucosal inflammation. Methods: In this multicentre trial, UC patients undergoing colonoscopy were prospectively enrolled. For the Modified Score (MS), the sum of Mayo Endoscopic Subscores (MESs) for five colon segments (ascending, transverse, descending, sigmoid and rectum) was calculated. The Extended Modified Score (EMS) was obtained by multiplying the MS by the maximal extent of inflammation. The Modified Mayo Endoscopic Score (MMES) was obtained by dividing the EMS by the number of segments with active inflammation. Colon biopsies were obtained from the rectum and sigmoid, as well as from all inflamed segments, by standard methods. Clinical activity was scored according to the Partial Mayo Score (PMS). Biological activity was scored according to C-reactive protein (CRP) and faecal calprotectin (FC) levels. Histological activity was scored according to the Geboes Score (GS). Results: One hundred and seventy-one UC patients (38% female, median age 47 years, median disease duration 13 years) were included. The MMES correlated significantly with the PMS ( r = 0.535), CRP ( r = 0.238), FC ( r = 0.730) and GS ( r = 0.615) (all p < 0.001). Median MMES scores were significantly higher in patients with clinical, biological or histological activity (all p ≤ 0.001) Conclusions: The MMES is an easy to use endoscopic index for UC that combines the severity analysis of the MES with disease extent, and correlates very well with clinical, biological and histological disease activity.

BACKGROUND & AIMS: Probiotic formulations of single species of bacteria have not been effective in preventing the recurrence of Crohn's disease after surgery. We investigated the ability of VSL#3, a mixture of 8 different bacterial probiotic species, to prevent Crohn's disease recurrence after surgery in a multicenter, randomized, double-blind, placebo-controlled trial. METHODS: Within 30 days of ileocolonic resection and re-anastomosis, patients with Crohn's disease were randomly assigned to groups given 1 sachet of VSL#3 (900 billion viable bacteria, comprising 4 strains of Lactobacillus, 3 strains of Bifidobacterium, and 1 strain of Streptococcus salivarius subspecies thermophilus) (n = 59) or matching placebo (n = 60). Colonoscopy was performed at days 90 and 365 to evaluate the neoterminal ileum for disease recurrence and obtain mucosal biopsies for cytokine analysis. Patients from both groups with either no or mild endoscopic recurrence at day 90 received VSL#3 until day 365. The primary outcome was the proportion of patients with severe endoscopic recurrence at day 90. RESULTS: At day 90, the proportion of patients with severe endoscopic lesions did not differ significantly between VSL#3 (9.3%) and placebo (15.7%, P = .19). The proportions of patients with non-severe lesions at day 90 who had severe endoscopic recurrence at day 365 were 10.0% in the early VSL#3 group (given VSL#3 for the entire 365 days) and 26.7% in the late VSL#3 group (given VSL#3 from days 90 through 365) (P = .09). Aggregate rates of severe recurrence (on days 90 and 365) were not statistically different, 20.5% of subjects in the early VSL#3 group and 42.1% in the late VSL#3 group. Patients receiving VSL#3 had reduced mucosal inflammatory cytokine levels compared with placebo at day 90 (P < .05). Crohn's disease activity index and inflammatory bowel disease quality of life scores were similar in the 2 groups. CONCLUSIONS: There were no statistical differences in endoscopic recurrence rates at day 90 between patients who received VSL#3 and patients who received placebo. Lower mucosal levels of inflammatory cytokines and a lower rate of recurrence among patients who received early VSL#3 (for the entire 365 days) indicate that this probiotic should be further investigated for prevention of Crohn's disease recurrence

Background & Aims: Common germline genetic variation in the 3′ region of myosin IXB ( MYO9B ) has been associated recently with susceptibility to celiac disease, with a hypothesis that MYO9B variants might influence intestinal permeability. These findings suggested the current study investigating a possible further role for MYO9B variation in inflammatory bowel disease. Methods: Eight single-nucleotide polymorphisms (SNPs) were selected to tag common haplotypes from the 35-kb 3′ region of MYO9B . These included the strongest celiac disease–associated variants reported in a Dutch cohort. These SNPs were studied in 3 independently collected and genotyped case-control cohorts of European descent (UK, Dutch, and Canadian/Italian), comprising in total 2717 inflammatory bowel disease patients (1197 with Crohn's disease, 1520 with ulcerative colitis) and 4440 controls. Results: Common variation in MYO9B was associated with susceptibility to inflammatory bowel disease in all 3 cohorts examined (most associated SNP, rs1545620; meta-analysis P = 1.9 × 10 -6 ; odds ratio, 1.2), with the same alleles showing association as reported for celiac disease. Conclusions: MYO9B genetic variants predispose to inflammatory bowel disease. Interestingly, rs1545620 is a nonsynonymous variant leading to an amino acid change (Ala1011Ser) in the third calmodulin binding IQ domain of MYO9B. Unlike previous variants (in other genes) reported to predispose to inflammatory bowel disease, the association at MYO9B was considerably stronger with ulcerative colitis, although weaker association with Crohn's disease also was observed. These data imply shared causal mechanisms underlying intestinal inflammatory diseases.

Multiple studies have established the superior diagnostic accuracy of video capsule endoscopy (VCE) for the diagnosis of small bowel (SB) Crohn's disease (CD). However, data on the clinical impact of VCE in patients with established CD are scarce. The aim of this study was to examine the impact and safety of VCE on the clinical management of patients with established CD.A retrospective, multicenter, cross-sectional study. The study cohort included consecutive patients with established SB CD who underwent VCE in 4 tertiary referral centers (1 Canada, 1 Sweden, and 2 United Kingdom) from January 2008 to October 2013. Patients were excluded if VCE was performed as a part of the initial diagnostic workup. The presence of SB mucosal inflammation was quantified using the Lewis score. Inflammatory biomarkers (C-reactive protein and fecal calprotectin) were measured and correlated with the Lewis score.The study included 187 patients. No SB inflammation was observed in 28.4%, mild-to-moderate inflammation in 26.6%, and moderate-to-severe inflammation in 45% of the patients (median Lewis score, 662; range, 0-6400). A change in management was recommended in 52.3% of the patients based on VCE findings. Elevated C-reactive protein, fecal calprotectin, or the combination of both were poorly correlated with significant SB inflammation. SB capsule retention occurred in 4 patients (2.1%).VCE in patients with established CD is safe, and the results often have a significant clinical impact. VCE should not be limited to CD patients with positive inflammatory markers because their predictive value for significant SB inflammation is poor.

Background Spontaneous cases of hepatic adverse events have been reported in patients with rheumatoid arthritis who were being treated with leflunomide, one of the newer disease-modifying antirheumatic drugs (DMARDs). We assessed the risk of hepatic events associated with the use of leflunomide and other DMARDs. Methods Two cohorts comprising 41,885 patients with rheumatoid arthritis who had been dispensed a DMARD between September 1, 1998, and December 31, 2001, were formed using claims databases. Follow-up was from the first dispensing date to the occurrence of a serious or nonserious hepatic event. A nested case-control approach was used to estimate adjusted rate ratios of hepatic events associated with DMARDs dispensed during the prior year, as compared with methotrexate monotherapy. Results There were 25 cases of serious hepatic events (rate, 4.9 per 10,000 per year) and 411 nonserious hepatic events (rate, 80.0 per 10,000 per year). There was no increase in the rate of serious hepatic events with either leflunomide (rate ratio [RR] = 0.9; 95% confidence interval [CI]: 0.2 to 4.9) or traditional DMARDs (RR = 2.3; 95% CI: 0.8 to 6.5). However, the rate was increased with biologic DMARDs (RR = 5.5; 95% CI: 1.2 to 24.6). The rate of nonserious hepatic events was also increased with biologic DMARDs (RR = 1.5; 95% CI: 1.0 to 2.3), but not with leflunomide (RR = 0.9; 95% CI: 0.7 to 1.3) and traditional DMARDs (RR = 1.1; 95% CI: 0.8 to 1.4). Conclusions We found no evidence of an excess risk of serious or nonserious hepatic events with the use of leflunomide as compared with methotrexate. Still, the increased risk observed with the new biologic DMARDs should be investigated further.

SUMMARY Background : The clinical course of Crohn's disease after the induction of remission with medical therapy is characterized by unpredictable relapse. Aim : To evaluate three surrogate markers, intestinal permeability, mucosal TNFα and nuclear factor (NF)-κB/IκBα expression, in order to determine the relationship of these parameters to clinical relapse. Methods : Thirty patients with active Crohn's disease were treated with a 10 week course of prednisone using a tapering dosing regimen. Intestinal permeability (lactulose/mannitol [L/M ratio]) was determined at baseline and at the end of prednisone tapering. TNFα production and the levels of expression of NF-κB/IκBα were measured in colonic mucosal biopsies obtained after the induction of remission. Results : Twenty-two patients (73%) achieved remission and 50% of patients experienced a clinical relapse during the ensuing 12 months. Treatment with prednisone resulted in a significant decrease in the L/M ratio. Of the patients that relapsed, 75% had a raised L/M ratio at the time of remission compared with 20% of patients with a normal L/M ratio (P

Objective The aim of this study was to identify determinants of nonadherence to medication in outpatients with established inflammatory bowel disease (IBD). Methods Ten gastroenterologists and 153 of their IBD patients participated in this prospective study. Demographic, clinical, and psychosocial characteristics, as well as patient-physician discordance, were assessed at an office visit. Nonadherence to medication was assessed 2 wk later. Separate generalized estimating equations were used to identify determinants of nonadherence. Results Physicians averaged 47.9 yr in age (range 30.1–57.5 yr), and 90% were male. Patients averaged 37.0 yr (SD = 15.1), and 87 (56.9%) were female. In all, 63 patients (41.2%) were nonadherent to medication; of these, 51 (81.0%) indicated unintentional nonadherence, 23 (36.5%) intentional nonadherence, and 11 (17.5%) both. Overall nonadherence was predicted by disease activity (OR = 0.55, p = 0.0022), new patient status (OR = 2.14, p = 0.0394), disease duration (OR = 0.50, p = 0.0001), and scheduling a follow-up appointment (OR = 0.30, p = 0.0059), whereas higher discordance on well-being was predictive only in psychologically nondistressed patients ( p = 0.0026 for interaction). Unintentional nonadherence was predicted by age (OR = 0.97, p = 0.0072), new patient status (OR = 2.80, p = 0239), and higher discordance on well-being in psychologically nondistressed patients ( p = 0.0504). Intentional nonadherence was predicted by disease duration (OR = 0.55, p = 0032), scheduling a follow-up appointment (OR = 0.12, p = 0.0001), certainty that medication would be helpful (OR = 0.99, p = 0.0409), and total patient-physician discordance (OR = 1.59, p = .0120). Conclusions These findings suggest that the therapeutic relationship, as well as individual clinical and psychosocial characteristics, influence adherence to medication.

BACKGROUND: The rate of serious complications is one marker of the quality of colonoscopy services.OBJECTIVE: To estimate the rate of serious complications of colonoscopy according to colonoscopy indication and polypectomy status.METHODS: A prospective cohort study of patients scheduled for colonoscopy who were recruited from seven endoscopy facilities across Montreal (Quebec) was conducted. Before colonoscopy, patients completed a brief questionnaire and provided their health insurance numbers. Colonoscopy indication was based on patient-reported medical history. Polypectomy status was obtained from provincial physician billing records (Régie de l’assurance maladie du Québec). Diagnoses and procedures associated with hospitalization in the 30 days following colonoscopy were obtained from the provincial hospitalization database (MedEcho).RESULTS: Of the 2134 patients enrolled (mean age 60.9 years, 50.1% male), 33 (1.55% [95% CI 1.06% to 2.16%]) were hospitalized within 30 days. One patient experienced bleeding following a colonoscopy that involved polypectomy and was diagnosed with carcinoma in situ of the rectum. Based on self-reported rectal bleeding in the previous six months, the colonoscopy was nonscreening. The provincial hospitalization data showed no occurrences of perforation, diverticulitis, myocardial infarction/stroke or death; thus, the rate of serious colonoscopy complications was 0.05% (95% CI 0.00% to 0.26%).DISCUSSION: The rate of serious colonoscopy complications requiring hospitalization was low and comparable with what is reported in the literature. The serious complication occurred subsequent to polypectomy and in a nonscreening colonoscopy.CONCLUSION: The findings support the relative safety of screening colonoscopy in persons without large bowel diseases and symptoms. However, future research to determine the rate of serious complications not requiring hospitalization is warranted to reassure decision makers of the safety of colonoscopy for colorectal cancer screening.

Summary Objective : Patients with ulcerative proctitis may have rectal mucosal properties different from healthy volunteers. This project compared the pharmacokinetics of rectally administered mesalazine in these two populations. Methods : In two separate studies, nine patients with ulcerative proctitis and 16 healthy volunteers received a single 500 mg mesalazine suppository and then 500 mg every 8 h for 5 days. Blood samples were collected for 12 h in healthy volunteers and 30 h in patients, and urine for 24 h in healthy volunteers and 30 h in patients. Rectal biopsies were performed 8 h after the last dose. Results : After a single dose to patients, mean mesalazine half-life (s.d.) was 5.0 (3.6) h. At steady-state, means (s.d.) were 89.1 (78.9) ng/mL for Cmin, 361.1 (240.8) ng/mL for Cmax, and 7.1 (7.3) h for half-life. Mean (range) rectal mesalazine concentrations were 167 (1.4–541.6) ng/mg tissue. After a single dose in healthy volunteers, mean (s.d.) half-life was 4.0 (4.7) h. At steady-state, means (s.d.) were 22.4 (61.6) ng/mL for Cmin, 359.4 (166.3) ng/mL for Cmax, and 0.9 (0.5) h for half-life. Conclusion : Mesalazine is released in the rectum of patients, with a bioavailability of about 40%. Tissue distribution is also appreciable. Both parameters appear higher than in healthy volunteers.

OBJECTIVE: The aim of this study was to identify the independent psychosocial correlates of patient-physician discordance in adult outpatients with inflammatory bowel disease. METHODS: This cross-sectional study was conducted in three university-affiliated tertiary care settings. Psychological distress, social support, perceived stress, and negative life events were assessed, as were demographic, lifestyle, and clinical characteristics. Patient-physician discordance was assessed with 10-item questionnaires. RESULTS: Ten gastroenterologists and 200 of their patients participated. Patients and their physicians disagreed most on discussion of personal issues. Patients with Crohn’s disease had statistically significantly higher discordance on disease activity and physical limitation, as well as higher average overall discordance scores than patients with ulcerative colitis. Mean discordance levels were similar across different physicians. Higher psychological distress and more perceived stress were independently associated with higher discordance after controlling for Crohn’s disease, active disease, being with the treating physician for less than 1 yr, and recommendation for further medical investigation. Psychological distress was the most important correlate of overall discordance. CONCLUSIONS: Increased physician awareness that psychologically distressed patients have difficulty processing of clinically relevant information may lead to improved doctor-patient communication during an office visit.

Patients with ileal pouches and ostomies present with management issues that are challenging to the clinician. Endoscopy plays a significant role in diagnosing and guiding therapy in such patients. Unfortunately, there are very few prospective studies that evaluates endoscopy in these situations. Nevertheless, it is clear that endoscopy remains a powerful tool that is important for diagnosis and therapy of complications unique to these surgical procedures. It seems prudent to advocate endoscopic cancer surveillance for patients with pouches and ostomies; however, it remains to be seen whether these efforts will ultimately have an impact on long-term patient morbidity and mortality.

Collagenous colitis and lymphocytic colitis are 2 atypical forms of inflammatory bowel disease that are relatively uncommon. Patients with these disorders usually present with chronic nonbloody, watery diarrhea. The diagnosis is based on specific histopathologic findings from colonic biopsy specimens. Given the relatively uncommon occurrence of these conditions, much about them still is unknown. This article outlines the current understanding of these atypical colitides and highlights advances in research and treatment. The first reported case of collagenous colitis was described in 1976 [39]. The patient, a middle-aged woman, presented with chronic watery diarrhea and was found to have a thickened subepithelial collagen band on colonic biopsy. Based on histologic similarity to collagenous sprue, the new disease entity was termed collagenous colitis. Subsequently the term microscopic colitis was introduced in a report of patients with chronic watery diarrhea, normal endoscopy, and a colonic biopsy specimen showing colitis without the distinctive collagen band [49]. In 1989, this disease was renamed lymphocytic colitis [37], and the term microscopic colitis was broadened to encompass all patients with histologic evidence of colitis and normal endoscopy. Given the similar presentations and histopathology of collagenous and lymphocytic colitis, it remains unresolved whether these colitides represent 2 ends of a disease spectrum or if they are separate entities.

Ustekinumab, an inhibitor of the p40 subunit of interleukins 12 and 23, is an effective treatment for patients with Crohn's disease (CD). Trough concentrations of tumor necrosis factor (TNF) antagonists and presence of anti-drug antibodies are associated with important clinical and endoscopic outcomes. We investigated associations between trough concentrations of ustekinumab and clinical, biomarker, and endoscopic outcomes of real-world patients with CD.We recruited 62 patients with CD who were either refractory or intolerant to TNF antagonists, treated with ustekinumab from April 2014 to September 2015. Patients received 90 mg of ustekinumab subcutaneously at weeks 0, 1, and 2 during induction and 90 mg every 4 or 8 weeks during maintenance. Clinical, biomarker, and endoscopic outcomes, trough concentrations of ustekinumab, and anti-drug antibodies were assessed at both week 10 postinduction therapy and at week 26 or later during maintenance therapy in a prospective longitudinal patient cohort or at week 26 or later during maintenance therapy in a cross-sectional patient cohort. Analysis was performed on data combined from both maintenance cohorts, which had similar outcomes at week 26 or later. A primary analysis determined if ustekinumab drug trough concentrations were associated with clinical response (reduction in Harvey Bradshaw Index score of 3 or greater), clinical remission (Harvey Bradshaw Index score5), steroid-free clinical remission, biomarker (serum level of C-reactive protein [CRP] or level of fecal calprotectin) reduction, biomarker normalization (serum level of CRP below 5 mg/L or level of fecal calprotectin below 200 μg/g), endoscopic response (simple endoscopic score for CD reduced by 50% or more), or endoscopic remission (simple endoscopic score for CD of 2 or less).At week 26 or beyond, 80.7% of patients had a clinical response, 66.1% were in clinical remission, 50.0% were in steroid-free clinical remission, 58.9% had an endoscopic response, and 19.6% were in endoscopic remission. The mean trough concentration of ustekinumab at this time point was higher in patients with an endoscopic response (4.7 μg/mL) than without (3.8 ug/mL; P = .03). An optimal ustekinumab threshold trough concentration at week 26 or later was found to be 4.5 μg/mL (area under the curve, 0.67). A greater proportion of patients with trough concentrations of ustekinumab above 4.5 μg/mL at week 26 or later had an endoscopic response (75.9%) than did patients with trough concentrations below this level (40.7%; P = .008). Patients with trough concentrations of ustekinumab above 4.5 μg/mL at week 26 or later also had a lower mean level of CRP (12.6 mg/L) than did patients with trough concentrations below this level (mean level of CRP, 23.9 mg/L; P = .04). We did not detect antibodies against ustekinumab in any patient.Ustekinumab therapy was effective in patients with CD who had not responded to or were intolerant to treatment with a TNF antagonist. Maintenance trough concentrations of ustekinumab above 4.5 μg/mL at 26 weeks or later were associated with biomarker reduction and endoscopic response.

Background: The FUT2 gene encodes fucosyltransferase 2 (FUT2), regulating intestinal antigen secretion and bacterial adherence. FUT2 homozygous mutations (FUT2M) and subsequent non-secretor status is associated with Crohn's disease (CD). A nucleotide polymorphism encoding a nonsense variant may predispose to CD by disrupting bacterial adherence or mucin fucosylation. This alters bacterial and mucous protection against pathogens, causing immune disequilibrium and mucosal inflammation. FUT2 products also interact with the IL 12/23 inflammatory pathways. Supporting genome wide association studies strongly associate homozygous FUT2 SNPs in strong linkage disequilibrium (LD) (rs602662 (A), rs676388 (C), rs492602 (G), rs504963 (A), rs601338 (A), rs485186 (G)), non-secretion, and CD. rs601338 (W143X) is the common null allele in Caucasians associated with the ABO non-secretory phenotype. Methods: We conducted a cross-sectional observational study of consecutive adult CD outpatients at the McGill University Health Center (2013–2015). Clinical and biochemical data were prospectively collected at a single routine office visit. We analyzed associations between CD and FUT2 mutation status. Results: Sixty-two CD patients were recruited. FUT2M homozygotes (rs602662, rs601338 or any mutation in LD) were detected in 27% of CD (17/62). Compared to Wild type (n=18), CD FUT2M homozygotes (n=17) had less penetrating CD (18% vs. 56%, p=0.02) and higher clinical remission without biologic or immunomodulator therapy (47% vs 6%, p=0.006). The latter was not observed in heterozygotes (22%, n=27, p=0.15). CD FUT2M homozygotes had similar disease location in the ileum (L2 p=0.31) and colon (L1, L3, p=0.56). Similarly, patients with homozygous rs601338 (n=15) had increased clinical remission rates without biologic or immunomodulator therapy (53% vs 5%, p=0.0016) compared to patients with wild type status (n=19). This was not observed in heterozygotes (24%, n=25, p=0.09). Both rs601338 homozygotes (20%) and heterozygotes (24%) had less penetrating disease than Wild type (53%, p=0.0495, 0.0478). rs601338 homozygotes (67%) but not heterozygotes (56%) had more luminal phenotype compared to non-mutants (32%, p=0.042). Conclusions: FUT2 homozygous mutations in CD was associated with a milder disease course: lower rates of penetrating disease and higher rates of remission without need for biologic or immunomodulator therapy. FUT2 may play a role in the natural history of CD through mofification of expression of adherence molecules and gut dysbiosis. Further studies are needed to confirm these findings.

BACKGROUND Among 10 provinces in Canada, Quebec has the second highest incidence of Crohn's disease (CD), based on data collected more than a decade ago. To date, there are no reports on the occurrence of ulcerative colitis (UC) and no updates on the occurrence of CD in Quebec. We sought to describe trends in the annual incidence and prevalence of inflammatory bowel disease in Quebec during 2001 to 2008. METHODS A population-based retrospective cohort study was conducted using the administrative health databases of Quebec. IBD cases were identified using a validated case definition requiring at least 1 hospitalization or 4 physician claims within a 2-year period. Incident cases were defined as individuals who had been free of inflammatory bowel disease for at least 2 years before the 2-year time span of the case definition. RESULTS We identified 24,377 CD and 15,346 UC cases. The mean age at diagnosis was 39 and 46 years for CD and UC, respectively. There was a significant decline in the annual incidence from 2001 to 2008 for both CD (P < 0.003) and UC (P < 0.001). No significant change with time was found in pediatric cases. The point prevalence in 2008 was 277 CD and 164 UC cases per 100,000 population. The average incidence was 17.4 CD cases per 100,000 person-years and 10.1 UC cases per 100,000 person-years. There was no predominance of urban or rural cases for either CD or UC. CONCLUSIONS During 2001 to 2008, annual incidence for both CD and UC declined in Quebec. There was no significant change with time in incidence for pediatric cases.

BACKGROUND Management of vitamin B(12) (cobalamin, Cbl) deficiency in inflammatory bowel disease (IBD) is often not evidenced-based because of uncertainty on whether it causes enough malabsorption to result in clinical disease. This systematic review examines whether IBD predisposes to Cbl deficiency. We provide an approach to the management of abnormal Cbl values in IBD based on current literature and consensus-based guidelines. METHODS An extensive search of the Ovid MEDLINE and EMBASE databases by independent reviewers identified 42 articles with a total of 3732 patients evaluating Cbl deficiency in IBD. RESULTS Crohn's disease without ileal resection, regardless of disease location in the ileum, did not increase the risk for Cbl deficiency. Ileal resections greater than 30 cm were associated with Cbl deficiency in Crohn's disease, whereas those less than 20 cm were not. The effects of 20 to 30 cm resections were inconsistent. Ulcerative colitis did not predispose to deficiency. All studies failed to use confirmatory biomarker testing as stipulated by diagnostic guidelines for Cbl deficiency. CONCLUSIONS This literature does not support an association of Crohn's disease in general, regardless of ileal involvement, with Cbl deficiency. Only ileal resections greater than 20 cm in Crohn's disease predispose to deficiency and warrant treatment. Based on these findings, we suggest a diagnostic and therapeutic algorithm. All findings and recommendations require verification in further studies using confirmatory biomarkers as per diagnostic guidelines for Cbl deficiency. Serum Cbl levels alone are likely insufficient to diagnose deficiency in asymptomatic patients.

Background and aims: Combination therapy with infliximab and azathioprine has been shown to be superior to either treatment alone in Crohn's disease (CD). However, the benefit of combining adalimumab with an immunomodulator remains controversial. The aim of this study was to compare the efficacy of adalimumab monotherapy with combination therapy for induction and maintenance of response and remission in CD using a meta-analysis of the current literature. Methods: We performed a systematic literature search using Medline, Embase, Cochrane and several other databases. Prospective randomized controlled trials, retrospective cohort and case-controlled studies were included. The primary outcomes included induction of response and remission (up to week 12), maintenance of clinical response and remission (1 year) and the need for dose escalation. Several subgroup and sensitivity analyses were performed. Results: Eighteen out of 2743 retrieved studies were included. A meta-analysis of 7 studies assessing induction of remission (n = 1984) showed that ADA monotherapy was inferior to combination therapy [OR = 0.78 (0.64–0.96), p = 0.02]. A meta-analysis of 4 studies revealed that combination therapy was not statistically different from ADA for maintenance of remission [OR = 1.08 (0.79–1.48), p = 0.48]. Combination therapy was also not different from ADA monotherapy in terms of requirement for dose escalation [OR = 1.13 (0.69–1.85), p = 0.62]. Conclusions: Combination therapy with ADA and immunomodulator was mildly superior to ADA monotherapy for induction of remission in CD. The rate of remission at 1 year and the need for dose escalation were similar in both groups. These findings should be interpreted with caution in view of possible confounders and should be further validated by randomized controlled trials. * Abbreviations : CD : Crohn's disease UC : ulcerative colitis ADA : adalimumab IFX : Infliximab AZA : azathioprine CDAI : Crohn's disease activity index HBI : Harvey Bradshaw Index 6-TGN : 6-thioguanine nucleotides

Background & Aims: Ulcerative colitis (UC) is a chronic relapsing infammatory bowel disease. We aimed to assess whether clinical, biological, and histologic parameters in quiescent UC predict time to clinical relapse. Methods: Seventy-four patients with clinically and endoscopically determined inactive UC were followed up for 1 year or for a shorter period if they had a relapse. Serum erythrocyte sedimentation rate; C-reactive protein, interleukin (IL)-1β, IL-6, and IL-15 values; anti-neutrophil cytoplasmic antibody titers; and rectal biopsy specimens were obtained at baseline, at 6 and 12 months, and/or at relapse. Multivariate survival analysis was performed to determine independent predictors of clinical relapse. Results: Twenty-seven patients relapsed (19/42 women; 8/32 men). Multivariate Cox regression analysis retained younger age ( P = 0.003; hazard ratio, 0.4 per decade), greater number of prior relapses in women ( P P = 0.003; hazard ratio, 4.5) on rectal biopsy specimens as predictors of shorter time to clinical relapse. Kaplan–Meier survival curves showed the 20–30-year-old age group and women with more than 5 prior relapses to be groups with shorter times to relapse. Conclusions: Younger age, multiple previous relapses (for women), and basal plasmacytosis on rectal biopsy specimens were independent predictors of earlier relapse. These findings may help identify patients with inactive UC who will require optimal maintenance medical therapy. GASTROENTEROLOGY 2001;120:13-20

Purpose: We prospectively evaluated a decrease in outflow obstruction caused by benign prostatic hyperplasia (BPH) with second generation thermotherapy.Materials and Methods: Transurethral microwave therapy was given with local anesthesia to 134 patients with urodynamically and cystoscopically documented obstruction by BPH and preserved detrusor function. Of 134 patients 67 (50%) had a general health score of 3 or greater.Results: Urgency was the main complaint during thermotherapy. After a median followup of 24 months (minimum 12) 100 patients were evaluable at 6 and 12 months. Of the initial 134 patients 17 (13%) who required additional treatment (repeat thermotherapy, transurethral prostatic resection, permanent cystostomy), 7 who died during followup for treatment unrelated reasons and 10 who were lost to followup or refused evaluation were excluded from further analysis.Mean International Prostate Symptom Score decreased from 22.5 before to 3.6 at 6 months after treatment and remained stable ...

SummaryBackground Tumour necrosis factor (TNF)-antagonists have an established role in the treatment of inflammatory bowel diseases (IBDs), however, subtherapeutic drug levels and the formation of anti-drug antibodies (ADAs) may decrease their efficacy. Aim The evidence supporting the use of therapeutic drug monitoring (TDM) based clinical algorithms for infliximab (IFX) and their role in clinical practice will be discussed. Methods The literature was reviewed to identify relevant articles on the measurement of IFX levels and antibodies-to-infliximab. Results Treatment algorithms for IBD have evolved from episodic monotherapy used in patients refractory to all other treatments, to long-term combination therapy initiated early in the disease course. Improved remission rates have been observed with this paradigm shift, nevertheless many patients ultimately lose response to therapy. Although empiric dose optimization or switching agents constitute the current standard of care for secondary failure, these interventions have not been applied in an evidence-based manner and are probably not cost-effective. Multiple TDM-based algorithms have been developed to identify patients that may benefit from measurement of IFX and ADA levels to guide adjustments to therapy. Conclusions Therapeutic drug monitoring offers a rational approach to the management of secondary failure to IFX. This concept has gained momentum based on evidence from case series, cohort studies and post-hoc analyses of randomised controlled trials.

BACKGROUND: Previously developed screening colonoscopy algorithms based on diagnostic and endoscopy procedural variables have not been sufficiently accurate for use in epidemiological and health services research.OBJECTIVE: To increase understanding of the administrative health database variables that could help to discern screening and nonscreening colonoscopy.METHODS: A qualitative study using physician focus groups was conducted in Montreal (Quebec), Calgary (Alberta) and Toronto (Ontario). Specialty-specific focus group sessions were held among family physicians and gastroenterologists – the physicians responsible for referring patients to and performing screening colonoscopy, respectively. Interview guides were developed to better understand physician clinical and billing practices. Discussions were audiotaped, transcribed verbatim and analyzed using the constant comparative approach.RESULTS: Forty family physicians and seven gastroenterologists participated in five focus group sessions. Patient variables included demographics (age) and medical history (colorectal cancer risk factors/symptoms, medication for colorectal cancer risk factors/symptoms, gastrointestinal disorders, severe disease). Clinical practice variables included timing of the colonoscopy (evenings, weekends, holidays, during hospitalization; same-day endoscopist consultation and colonoscopy), use of services (hospitalization, annual examination, transfer from other facility) and procedure use patterns (large bowel or other medical/surgical procedure before and subsequent to colonoscopy). However, wide variability in clinical and billing practices will likely preclude the development of a reasonably accurate screening colonoscopy algorithm. Physicians suggested adding a screening colonoscopy code to the administrative health data.CONCLUSIONS: Failure to acknowledge the limitations of the provincial administrative health databases to identify screening colonoscopy may lead to incorrect conclusions and the establishment of inappropriate health care policies.

Successful medical treatment of inflammatory bowel disease depends on the judicious use of the therapeutic agents available. This, in turn, depends on the severity of patients' symptoms and the extent and location of the disease. This article describes the drug therapy and approach to specific clinical presentations encountered in patients with ulcerative colitis and Crohn's disease.

Despite the chronic and recurring nature of ulcerative colitis and Crohn’s disease, these two disorders can present acutely as true medical emergencies. The urgent complications include both intestinal and extraintestinal disease. The successful management of such emergencies will depend on early diagnosis and the judicious and timely use of both medical and surgical therapy.

The histopathology of the mucosal lesions in ulcerative colitis suggests that cellular immune hyperactivity plays a role in the pathogenesis of ulcerative colitis. The role of colonic mucosal cytotoxic lymphocytes in ulcerative colitis is highly controversial. In vitro determinations of cytotoxic lymphocyte function vary according to the experimental conditions and target cells employed. Transcription of the cytotoxic molecules granzyme B and perforin are specific for activated cytotoxic lymphocytes. We investigated whether activated cytotoxic lymphocytes are present in ulcerative colitis lesions via identification of granzyme B, perforin, and interleukin 2 transcripts. RNA was extracted from endoscopic colonic biopsies taken from normal and ulcerative colitis patients. An aliquot was reverse transcribed, followed by gene amplification in the polymerase chain reaction. A competitive template was incorporated within the reaction permitting the quantitation of specific mRNA species. Granzyme B and perforin levels of reverse transcribed cDNAs (RT-cDNAs) were significantly elevated in active ulcerative colitis as compared to normal colonic tissues (p = 0.0081 and p = 0.0018, respectively) when calculated as a ratio with the RT-cDNA of the constitutively expressed gene GAPDH. Interleukin 2 mRNA measurements did not vary between normal and UC samples to a statistically significant degree. These data suggest heightened lymphocyte cytotoxic function within ulcerative colitis mucosal lesions.

Airway diseases are the most commonly described lung manifestations of inflammatory bowel disease (IBD). However, the similarities in disease pathogenesis and the sharing of important environmental risk factors and genetic susceptibility suggest that there is a complex interplay between IBD and airway diseases. Recent evidence of IBD occurrence among patients with airway diseases and the higher than estimated prevalence of subclinical airway injuries among IBD patients support the hypothesis of a two-way association. Future research efforts should be directed toward further exploration of this association, as airway diseases are highly prevalent conditions with a substantial public health impact.

The IBD5 locus is a genetic risk factor for IBD, particularly Crohn's Disease, coding for the organic cation/carnitine transporters (OCTN1 and 2). Two variants of OCTN are associated with susceptibility to Crohn's Disease. Modified transport of carnitine in vitro has been reported for a polymorphism of OCTN1. The aim was to investigate the function of intestinal OCTNs in IBD in relation to genetic polymorphisms.Intestinal tissue was obtained from endoscopic biopsies and surgical resections from IBD patients (n=33 and 14, resp.) and controls (n=22 and 14, resp.). OCTN protein levels were measured in intestinal biopsies and carnitine transport was quantified in intestinal resections.OCTN1 protein levels were significantly higher in ileal versus colonic tissue (2.95% ± 0.4 vs 0.66% ± 0.2, resp.; p0.0002). OCTN1 expression was higher in Crohn's disease patients with mutant homozygous or heterozygous genotypes (0.6% ± 0.1 vs 3% ± 0.8, resp., p0.02). Carnitine transport was very rapid and Na+ dependent (10s). It was not different comparing Crohn's Disease and control groups (0.45 ± 0.12 vs 0.51 ± 0.12 nM carnitine/mg prot/min, resp.). Carnitine transport tended to be higher in subjects with mutant homozygous and heterozygous OCTN1 and OCTN2 genotypes (0.19 vs 0.59 and 0.25 vs 0.6, respectively).The present data reveal that OCTN protein levels appear to be similar in intestinal tissue from Crohn's Disease patients and controls. Overall, ileal carnitine transport appears to as well equal in Crohn's Disease and control groups. However, there was a trend towards higher carnitine transport in subjects with OCTN1 and OCTN2 mutations.

s of the 9th Congress of ECCO the European Crohn’s and Colitis Organisation S3 Results: Twenty-one centers (1084 patients) were assigned to ECI and 18 (898 patients) to CM. The mean age of the patients was 44.2 in the ECI group and 44.1 in the CM group. Mean HBS scores were 4.1 in both groups. The proportion of patients in the ECI and CM groups who received combination of antimetabolite/TNF-antagonist by 12 months was 15.1% and 6.5% P< 0.001) and 19.7% and 9.6% by 24 months (P< 0.001). Mean % (SD) remission rates in the ECI and CM groups were 66 (14) and 62 (17) at 12 months (P= 0.65) and 73 (8) and 65 (17) at 24 months (P= 0.35). However, highly significant and clinically important differences in the rates of complications, surgeries, and the combined outcome of hospitalizations, complications, and surgeries were observed in favor of ECI over 24 months (Figure 2). The 24 month actuarial estimates for the combined outcome were 27.7% and 35.1% in the ECI and CM groups, respectively (hazard ratio adjusted for CD caseload and country: 0.74 [0.62, 0.87, P< 0.001]). Figure 2. Hospitalizations, complications*, and surgeries for patients in the ECI and CM groups over 24 months. *Abscess, new fistula, extra-intestinal manifestations of CD and serious AEs. Conclusions: Community-based data indicate that (1) a symptom based conventional approach to CD management may not be optimal and (2) ECI may be more effective in preventing CD-related complications. OP005 Is elderly-onset ulcerative colitis a different entity? Natural disease course and treatment response compared to adult-onset disease in the population-based IBD-SL cohort S. Jeuring1,2 *, T. Van den Heuvel1,2, M. Zeegers3,4, W. Hameeteman1, M. Romberg-Camps5, L. Oostenbrug6, A. Masclee1,2, D. Jonkers1,2, M. Pierik1,2. 1Maastricht University Medical Center+, Internal Medicine Division Gastroenterology-Hepatology, Maastricht, Netherlands, 2Maastricht University Medical Center+, NUTRIM, School for Nutrition, Toxicology and Metabolism, Maastricht, Netherlands, 3University of Birmingham, Epidemiology and Public Health, Birmingham, United Kingdom, 4Maastricht University Medical Center+, Complex Genetics, Cluster of Genetics and Cell Biology, Maastricht, Netherlands, 5ORBIS Medical Centre, Gastroenterology and Hepatology, Sittard, Netherlands, 6Atrium Medical Center, Internal Medicine and Gastroenterology, Heerlen, Netherlands Background: Population ageing is a worldwide demographic phenomenon. Since the incidence of ulcerative colitis (UC) is increasing, elderly-onset UC will become more prevalent in the near future. It is unclear whether elderly-onset UC is a different phenotypic subgroup, requiring different treatment strategies. Information on disease course and treatment response of elderly-onset UC patients is scarce and conflicting, and often derived from small, selected UC populations. Therefore, we aimed to compare disease course and treatment response between adultand elderly-onset UC in our population-based

Vitamin D signaling through its nuclear vitamin D receptor has emerged as a key regulator of innate immunity in humans. Here we show that hormonal vitamin D, 1,25-dihydroxyvitamin D(3), robustly stimulates expression of pattern recognition receptor NOD2/CARD15/IBD1 gene and protein in primary human monocytic and epithelial cells. The vitamin D receptor signals through distal enhancers in the NOD2 gene, whose function was validated by chromatin immunoprecipitation and chromatin conformation capture assays. A key downstream signaling consequence of NOD2 activation by agonist muramyl dipeptide is stimulation of NF-kappaB transcription factor function, which induces expression of the gene encoding antimicrobial peptide defensin beta2 (DEFB2/HBD2). Pretreatment with 1,25-dihydroxyvitamin D(3) synergistically induced NF-kappaB function and expression of genes encoding DEFB2/HBD2 and antimicrobial peptide cathelicidin in the presence of muramyl dipeptide. Importantly, this synergistic response was also seen in macrophages from a donor wild type for NOD2 but was absent in macrophages from patients with Crohn disease homozygous for non-functional NOD2 variants. These studies provide strong molecular links between vitamin D deficiency and the genetics of Crohn disease, a chronic incurable inflammatory bowel condition, as Crohn's pathogenesis is associated with attenuated NOD2 or DEFB2/HBD2 function.

The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 x 10(-9)), 22q12 (rs2412973, P = 1.55 x 10(-9)), 10q22 (rs1250550, P = 5.63 x 10(-9)), 2q37 (rs4676410, P = 3.64 x 10(-8)) and 19q13.11 (rs10500264, P = 4.26 x 10(-10)). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn's disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD.

Introduction Erectile dysfunction (ED) is distressing and can affect a couple's relationship. Aim To investigate partner awareness of ED, relationship problems, and the effects of tadalafil treatment over 12 months. Methods The Determinants of Continued Use of Tadalafil study is a prospective 12‐month European observational study in patients with ED initiating or changing treatment to on‐demand tadalafil. A total of 1,900 patients were enrolled in eight countries. Assessments were made on predefined treatment outcomes in a routine clinical setting. Main Outcome Measures At baseline, 1, 6, and 12 months, patients were asked about relationship problems (unspecified), partner awareness and support of consultation, and partner sexual problems. Data were analyzed for patients continuing tadalafil at 12 months. Results At baseline, 96% of patients had a partner, 80% of partners supported an ED consult, and 73% were aware of the consultation. Relationship problems were reported by 17% of patients at baseline. At 12 months, 84% of patients were still taking tadalafil. Of these, 19% reported relationship problems at baseline. After 12 months of treatment with tadalafil, 4% of patients still reported perceived problems. Factors associated with no relationship problems at 12 months were: at baseline, no previous ED treatment, partner in poor health; and at 12 months a lower ED severity. If the partner was felt to have a sexual problem at 12 months, relationship improvement was less likely. Further, 3% of patients developed relationship problems during treatment. Factors associated with developing a relationship problem were: a history of pelvic surgery at baseline, a different partner at 12 months than at baseline, and a partner with a sexual problem at 12 months. Conclusions Improvement of ED with tadalafil was associated with reduced relationship problems, suggesting that problems were associated with ED and resolved with treatment. Verheyden B, Roumeguere T, Bitton A, Belger M, and Schmitt H. Effects of 12‐month tadalafil therapy for erectile dysfunction on couple relationships: Results from the DETECT study. J Sex Med 2009;6:3458–3468.

Phenotype characteristics of inflammatory bowel disease (IBD) may differ significantly among ethnic subpopulations. The aim of this study was to characterize the IBD phenotype in French Canadians, the most prominent founder population in North America.Using well-characterized phenotype data in the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)-IBD Genetics Consortium repository on patients with IBD, we compared phenotypic characteristics of 202 French Canadians with those of 1,287 other Caucasian patients. These included diagnosis, anatomical location, disease behavior, extraintestinal manifestations, surgical history, and family history of IBD.French-Canadian patients with Crohn's disease (CD) were less likely to have stricturing disease (11 vs. 21%, P=0.005; odds ratio (OR): 0.45, 95% confidence interval (95% CI): 0.24-0.85). Using a stringent definition of ethnicity (three out of four grandparents being French Canadians, as opposed to self-report, n=148), French Canadians had a tendency toward developing fistulizing CD (37 vs. 28%, P=0.07), and there was an increased prevalence of sacroiliitis among those with IBD (4 vs. 2%, P=0.045). Among French Canadians, the numbers of current smokers in CD (40 vs. 25%, P=0.006) and former smokers in ulcerative colitis (UC) (35 vs. 20%, P=0.03) were significantly higher. The prevalence of one of the three main variants of nucleotide-binding oligomerization domain containing 2 (NOD2) single-nucleotide polymorphisms (SNPs) among French-Canadian CD patients was 43.2%. The 3020insC SNP correlated with small bowel disease in French Canadians (25 [corrected] vs. 0%, P=0.006).French Canadians show an IBD phenotype profile distinct from other Caucasian IBD populations, with an accentuated association between smoking status and IBD. This unique profile may have implications regarding the need for a different approach to the management of IBD in this population.

Background: Crohn's disease (CD) is an idiopathic inflammatory bowel disease (IBD). We aimed to determine the prevalence and incidence of CD in Quebec and characterize the demographic and health-related factors associated with this disease. Methods: We identified CD cases in the provincial administrative databases for the years 1993–2002. The CD prevalence and incidence rates were estimated respectively for the periods 1993–2002 and 1998–2000. We validated the identified cases using clinically confirmed IBD cases. Predictor variables of CD were analyzed using the Poisson regression model to explain the variation in CD incidence rates across Quebec. Results: In all, 21,172 patients fulfilled the CD case definition for the period. The age and sex standardized average prevalence rate for 1993–2002 was 189.7 cases / 100,000 population and the age and sex standardized incidence rate of CD for the 1998–2000 period was 20.2 cases / 100,000 person-years. The female/male cases ratio among incident cases was 0.74 for the 0–14-year-old group, 1.30 for the 15–64-year-old group, and 1.77 for the cases older than 65 years old. After adjustment, independent predictors of CD incidence were: incidence of 5 reportable enteric diseases, proportion of individuals of Jewish ethnicity, and proportion of immigrant people. Conclusions: The identified predictors of CD explained 20% of the regional variance in the incidence rate of CD in the Quebec population. Other factors such as genetic susceptibility to CD or the effect of an environmental cause should be taken into consideration in the models to explain the residual variance. (Inflamm Bowel Dis 2008)

The hypothesis that measles virus (MV) is implicated in the pathogenesis of Crohn’s disease (CD) was initiated by Wakefield et al 1 in the early 1990s. Several other reports soon followed, which suggested the presence of MV in CD samples using electron microscopy, immunohistochemical analysis, in situ hybridisation and nested PCR.2–4 Controversy in response to this claim resulted in falling measles vaccination rates, mainly in the UK. Immediate concerns were raised regarding several aspects of these studies, including reagent specificity.5 In addition, several groups were unable to replicate their findings using a range of PCR techniques.6–9 In 1998 and 2002, the initial investigators again raised concerns over MV persistence in bowel tissue, this time in children with autism.10 These allegations further damaged confidence in MV vaccination programmes. As the primer pairs that had been used to implicate MV in inflammatory bowel disease (IBD; Kawashima)4 and autism (Uhlmann)10 were not included in the negative studies,6–9 it could still be argued that the negative results arose due to the use of incorrect or suboptimal primers. We therefore used the Kawashima and Uhlmann primers in an attempt …

Background: The NIDDK IBD Genetics Consortium (IBDGC) collects DNA and phenotypic data from inflammatory bowel disease (IBD) subjects to provide a resource for genetic studies. No previous studies have been performed on the reliability and validity of phenotypic determinations in either Crohn's disease (CD) or ulcerative colitis (UC) using primary records. Our aim was to determine the reliability and validity of these phenotypic assessments. Methods: The de-identified records of 30 IBD patients were reviewed by 2 phenotypers per center using a standard protocol for phenotypic assessment. Each phenotyper evaluated 10 charts on 2 occasions 5 months apart. Reliability was expressed as the kappa (κ) statistic. Performance characteristics were determined by comparison to a consensus-derived “gold standard” and by generation of receiver operating characteristic (ROC) curves. Results: Agreement for diagnosis was excellent (κ = 0.82; 95% confidence interval [CI]: 0.71–0.92). Agreement for CD location was good for jejunal, ileal, colorectal, and perianal disease with κ between 0.60 and 0.74 but was fair for esophagogastroduodenal (κ = 0.36). Agreement for UC extent (κ = 0.67; 95% CI: 0.48–0.85), and CD behavior (κ = 0.67; 95% CI: 0.49–0.83) were very good. Area under the ROC curves was greater than 0.84 for diagnosis, CD behavior, UC extent, and ileal and colonic CD location. Conclusions: IBD phenotype classification using a standard protocol exhibited very good to excellent inter- and intrarater agreement and validity. This study highlights the importance of standard protocols in generating reliable and valid phenotypic assessments. The data will facilitate estimates of phenotyping misclassification rates that should be considered when making inferences from IBD genotype–phenotype studies. (Inflamm Bowel Dis 2007)

Background & Aims The medical management of ulcerative colitis (UC) has improved through the development of new therapies and novel approaches that optimize existing drugs. Previous Canadian consensus guidelines addressed the management of severe UC in the hospitalized patient. We now present consensus guidelines for the treatment of ambulatory patients with mild to severe active UC. Methods A systematic literature search identified studies on the management of UC. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a working group of specialists. Results The participants concluded that the goal of therapy is complete remission, defined as both symptomatic and endoscopic remission without corticosteroid therapy. The consensus includes 34 statements focused on 5 main drug classes: 5-aminosalicylate (5-ASA), corticosteroids, immunosuppressants, anti–tumor necrosis factor (TNF) therapies, and other therapies. Oral and rectal 5-ASA are recommended first-line therapy for mild to moderate UC, with corticosteroid therapy for those who fail to achieve remission. Patients with moderate to severe UC should undergo a course of oral corticosteroid therapy, with transition to 5-ASA, thiopurine, anti-TNF (with or without thiopurine or methotrexate), or vedolizumab maintenance therapy in those who successfully achieve symptomatic remission. For patients with corticosteroid-resistant/dependent UC, anti-TNF or vedolizumab therapy is recommended. Timely assessments of response and remission are critical to ensuring optimal outcomes. Conclusions Optimal management of UC requires careful patient assessment, evidence-based use of existing therapies, and thorough assessment to define treatment success.

Inflammatory bowel disease (IBD), comprising primarily of Crohn's disease (CD) and ulcerative colitis (UC), is increasingly prevalent in racial and ethnic minorities. This study was undertaken to characterize racial differences in disease phenotype in a predominantly adult population.Phenotype data on 830 non-Hispanic white, 127 non-Hispanic African American, and 169 Hispanic IBD patients, recruited from six academic centers, were abstracted from medical records and compiled in the NIDDK-IBD Genetics Consortium repository. We characterized racial differences in family history, disease location and behavior, surgical history, and extraintestinal manifestations (EIMs) using standardized definitions.African American CD patients were more likely than whites to develop esophagogastroduodenal CD (OR = 2.8; 95% CI: 1.4-5.5), colorectal disease (OR = 1.9; 95% CI: 1.1-3.4), perianal disease (OR = 1.7; 95% CI: 1.03-2.8), but less likely to have ileal involvement (OR = 0.55; 95% CI: 0.32-0.96). They were also at higher risk for uveitis (OR = 5.5; 95% CI: 2.3-13.0) and sacroiliitis (OR = 4.0; 95% CI: 1.55-10.1). Hispanics had higher prevalence of perianal CD (OR = 2.9; 95% CI: 1.8-4.6) and erythema nodosum (3.3; 95% CI: 1.7-6.4). Among UC patients, Hispanics had more proximal disease extent. Both African American and Hispanic CD patients, but not UC patients, had lower prevalences of family history of IBD than their white counterparts.There are racial differences in IBD family history, disease location, and EIMs that may reflect underlying genetic variations and have important implications for diagnosis and management of disease. These findings underscore the need for further studies in minority populations.