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The aim of this study was to assess the relationship of serum vedolizumab concentrations (SVC) during induction and endoscopic remission in patients with inflammatory bowel diseases (IBD) after 52 weeks of therapy with vedolizumab. We also sought to assess the incidence of antibody to vedolizumab (ATV) formation, the effect of ATV on drug pharmacokinetics and efficacy, and identify variables associated with SVC through the first 30 weeks of treatment. This is a prospective cohort study of patients with active IBD initiating standard therapy with vedolizumab. Collected variables included demographics, clinical disease activity, biomarkers, pre-infusion SVC, and ATV measured at weeks 2, 6, 14, 22, and 30. Primary outcome was steroid-free endoscopic remission at week 52. Fifty-five patients were included. Patients that achieved steroid-free endoscopic remission by week 52 had higher SVC at weeks 2, 6, 14, 22, and 30, but only achieved statistical significance at weeks 2 and 6. Only 3 out of the 55 study subjects (5.5%) had detectable ATV through the follow-up. Overall, there were a positive correlation between SVC and serum albumin and a negative correlation with C-reactive protein, fecal calprotectin, and body mass. Vedolizumab concentrations ≥ 23.2 mcg/ml at week 2 were associated with endoscopic remission at week 52 (OR 8.8 [95% CI 2.6–29.7], p

Inflammatory bowel diseases (IBD) include ulcerative colitis and Crohn’s disease. These conditions commonly affect patients during their childbearing years. There are many questions that arise when a female patient with inflammatory bowel disease is attempting pregnancy. Important considerations include the safety of continuing medications during and after pregnancy, the risk of stopping drugs during pregnancy, and the effects of the medications on the newborn. Most pharmacologic agents are safe to continue during pregnancy; however, some drugs such as methotrexate are contraindicated. The anti-tumor necrosis factor biologic agents infliximab and adalimumab have the most robust data regarding their safe use in pregnancy and while breastfeeding. More experience is needed with newer medications. Another important question that can often arise is the potential effect that IBD can have on fertility. Patients with IBD who have not undergone surgery have fertility rates similar to those patients without IBD, though voluntary childlessness is higher in those patients with IBD. Female patients who have undergone surgery for their IBD, such as total colectomy with creation of an ileal pouch-anal anastomosis (IPAA), do have decreased fertility rates compared to those patients without IBD.

Background and Aims Patients with Crohn’s disease (CD) may require small bowel resections. Unfortunately, some of these patients may develop post-operative small bowel obstructions (SBO). Many clinicians perceive ileal resections dramatically increase the risk of developing SBO in the future, but the incidence and risk factors to developing SBO are poorly described. The primary aim of this study is to document the incidence and factors associated with the development of SBO not related to recurrence of disease in CD patients that undergo ileal resection. We also sought to assess long-term outcomes of this complication. Methods We performed a retrospective cohort study including patients aged 18 years or older with CD, who have had ileocecal resection with ileocolonic anastomosis or segmental small bowel resection. Data abstracted included demographics, phenotype and therapies of CD, disease recurrence post-ileal resection and multiple surgical variables. The primary outcome was the development of SBO within 5 years post-surgery not including obstructions secondary to recurrence of CD. Results 92 total patients were included in the analysis. All had a colonoscopy within a year of the surgery. The mean Rutgeerts score was 0 (interquartile range [IQR] 0 to 2) and the mean short endoscopic score was 0 (IQR 0 to 4). The remainder of baseline characteristics are shown in Table 1. At 6 months, 1 year, and 5 years, the rate of SBO was 4/92 (4%), 6/92 (6.5%), and 15/92 (16%), respectively. Throughout follow-up, only 5 patients had an SBO attributed to intra-abdominal adhesions and only 2 patients required surgical lysis of adhesions. Patients that were found to have histologic inflammation in the margins of the resected bowel specimen had a significantly higher chance of developing an SBO within 5 years of the initial surgery (OR: 4.5 [95%CI: 1.3–15.3], p=0.02 - Table 2). Conversely, patients with either active endoscopic and/or radiologic inflammation on post surgical surveillance colonoscopy did not have a higher risk of developing an SBO within 5 years of the initial surgery (p=0.37). Finally the length of bowel resected at the index surgery was not associated with the development of an SBO (AUC: 0.62, p=0.18). Conclusions The incidence of SBO after ileal resection in CD is low and resolves with medical management on most cases. Inflammation in the margins of the resected bowel and previous bowel resections were associated with new SBO within 5 years. These results must take into account the study population were monitored and cannot be extrapolated to those patients that lost follow-up.

Background There is little long-term research (≥12 months) in ulcerative colitis (UC) and Crohn’s disease (CD) patients investigating the impact on clinical effectiveness of combined (combo) therapy of vedolizumab (VDZ) plus immunomodulators/immunosuppressants (IMMs) compared with VDZ monotherapy. Research suggests the use of concomitant aminosalicylates [5-ASAs] in UC may not bolster effectiveness. Finally, it is unclear if the safety profile differs between VDZ monotherapy and combo therapy. This study described clinical effectiveness and safety outcomes in patients with UC or CD treated with first-line biologic VDZ as monotherapy or combo therapy with IMMs or 5-ASAs (UC only). Methods This was a real-world, multi-country (Canada, Greece and the USA), retrospective chart review study of biologic-naïve UC and CD patients (≥18 years old) treated with VDZ (initiated Tx May 2014–March 2018). Data were collected from Tx initiation to the earliest of death and chart abstraction date. Cumulative rates of clinical effectiveness outcomes over 24 months (Tx persistence, clinical response and clinical remission) were estimated using the Kaplan-Meier method with unadjusted comparisons conducted using the log-rank test. Clinical response and remission were assessed from standard disease measures reported in medical records. Analyses of unadjusted incidence rates (per 100 person-years [PYs]) of disease exacerbations, disease-related surgeries, serious adverse events (SAEs) and serious infections (SIs) were performed. For these analyses in monotherapy vs. VDZ+IMMs, UC and CD patients were combined due to restrictions of sample size and a number of events. Results This analysis included 318 patients treated with VDZ (monotherapy: UC = 53, CD = 108; VDZ+IMMs: UC = 22, CD = 24; VDZ+5-ASAs: UC = 111). There were no observed differences in age, sex or disease duration between patients on monotherapy vs. VDZ+IMMs or vs. VDZ+5-ASAs. Data trends in effectiveness outcomes were similar in monotherapy vs. VDZ+IMMs over 24 months (Figure 1). Tx persistence (monotherapy: 71.6%; VDZ+5-ASAs: 82.7%; p = 0.40), clinical remission (monotherapy: 54.3%; VDZ+5-ASAs: 87.7%; p = 0.37) and clinical response (monotherapy: 81.7%; VDZ+5-ASAs: 92.2%; p = 0.54) were also similar between monotherapy and VDZ+5-ASAs over 24 months. Safety outcomes were similar between groups (Figure 2). Conclusion Though sample sizes were small, the unadjusted trends in the results of this long-term real-world study suggest that biologic-naïve UC or CD patients treated with VDZ alone may have similar clinical effectiveness outcomes to patients receiving VDZ+IMMs. Trends in data also suggest that in patients with UC, VDZ+5-ASAs may not be more effective than VDZ alone.

Background Crohn’s disease (CD) can lead to complications that impact treatment (Tx) decisions and its clinical effectiveness. The objective of this analysis was to compare clinical effectiveness outcomes of CD patients treated with first-line biologic vedolizumab (VDZ) who did not have a complicated disease phenotype (non-complicated) to VDZ patients who had complications (complex disease). Methods This was a retrospective real-world cohort study of biologic-naïve CD patients (≥18 years old) in Canada, Greece and the USA who initiated VDZ Tx between May 2014 and March 2018. Data were collected from Tx initiation to the earliest of chart abstraction date or death. The non-complicated CD was defined as patients who had mild or moderate disease severity and no active fistula at Tx initiation, had no prior CD-related surgeries since diagnosis and no CD-related hospitalisations within 12 months prior to Tx initiation. The complex disease cohort encompassed all other CD patients. Cumulative rates of clinical effectiveness outcomes over 24 months (Tx persistence, clinical response and clinical remission) were estimated using the Kaplan–Meier method. Using pre-defined hierarchical algorithms, clinical response and clinical remission were assessed from standard disease measures reported in the medical records. Results This analysis included 218 CD patients treated with VDZ (non-complicated: 64 (29.3%); complex: 154 (70.6%) from 37 sites. Mean (SD) age at Tx initiation: non-complicated, 46.2 (15.8); complex, 54.0 (16.7); male: non-complicated, 45.3%; complex, 55.2%. Cumulative rates of clinical response were significantly greater in non-complicated than complex disease patients over 24 months (non-complicated: 93.0%, complex: 76.0%, p < 0.01) (Figure 1). Tx persistence (non-complicated: 76.7%, complex: 66.6%, p = 0.68) (Figure 2) and clinical remission (non-complicated: 81.9%, complex: 73.5%, p = 0.36) (Figure 1) were not significantly different between the two cohorts over 24 months. Fewer patients had data for mucosal healing over 24 months, and it was also not significantly different between groups at 12 months (non-complicated: 66.4%, complex: 60.2%, p = 0.95). Conclusion A high proportion of patients (70%) had a complex disease when VDZ Tx was initiated but those with non-complicated phenotype had a higher response rate. To help guide physicians in positioning the optimal Tx for biologic-naïve CD patients, it is important to identify the sub-group of patients who can most benefit from VDZ Tx. The results of this real-world study suggest that the biologic-naïve, non-complicated CD patients benefit more from VDZ treatment compared with those with disease complications.

Background Reliable biomarkers of ulcerative colitis (UC) disease activity may be useful in clinical trials and practice. Etrasimod is an oral, selective, sphingosine 1-phosphate receptor modulator with efficacy in a 12-week, phase 2, double-blind (DB), randomised, controlled trial in adult patients with moderately-to-severely active UC (OASIS; NCT02447302). Patients who completed the DB study were eligible to enrol in an open-label extension (OLE; NCT02536404) and receive etrasimod 2 mg once daily for up to an additional 34 weeks. The aim of this post-hoc analysis was to assess the correlation of sequential faecal calprotectin (FC) and C-reactive protein (CRP) levels throughout the DB study and OLE with clinical and endoscopic outcomes at end of treatment (EOT) in the OLE. Methods In the DB study, patients received etrasimod 1 mg, etrasimod 2 mg or placebo. The OLE evaluable cohort comprised patients who received etrasimod 2 mg throughout the OLE. The modified intention-to-treat (mITT) population comprised patients with non-missing assessments. EOT was the last observation for each patient, occurring at week 46 (OLE week 34) for study completers or at last visit for patients who discontinued or had missing data. Endpoints were modified Mayo Clinic score (mMCS; range 0–9; including endoscopy, rectal bleeding [RB], and stool frequency [SF]); clinical remission (endoscopic subscore ≤1 [with absence of friability], RB ≤1, and SF score ≤1 with ≥1 point decrease from DB baseline); clinical response (clinical remission or decrease in mMCS of ≥2 points and ≥30% decrease from DB baseline, with either a RB decrease of ≥1 or RB score of ≤1); and endoscopic improvement (subscore ≤1). FC and CRP were measured longitudinally to EOT. Comparisons between subgroups were assessed with a Wilcoxon rank-sum test (2-sided P values). Analysis of correlation between variables was conducted using the Spearman’s rank coefficient. Results The evaluable cohort included 105 patients, 31 of whom received etrasimod 2 mg throughout both DB and OLE periods. At EOT 70%, 35% and 45% of patients in the mITT evaluable cohort had clinical response, clinical remission and endoscopic improvement, respectively. Differences in FC and CRP levels between patients with and without clinical remission at EOT are shown in Figures 1 and 2, respectively for patients who received etrasimod 2 mg throughout both the DB and OLE periods. Correlation analyses of FC and CRP with clinical (mMCS) and endoscopic disease activity and with each other are shown in Table 1. Conclusion FC and CRP appear to correlate with clinical and endoscopic outcomes over long-term treatment with etrasimod. Additional validation is needed to determine their utility in treat-to-target management strategies.

The original version of the article unfortunately contained an error in a percentage value in Results section of Abstract.

The original version of the article unfortunately contained a couple of errors. In 'methods' section, in 'Outcomes' subsection, the sentence 'Endoscopic remission was defined as an SESCD ≤ 2 in patients with CD and an EMS ≤ 2 in UC patients while off corticosteroids.'

Background Optimal levels of adalimumab (ADA) have not been defined according to the ultimate goal of inflammatory bowel disease treatment--histologic and/or endoscopic healing. The aim of this study was to assess the relationship between random serum ADA levels and histologic and endoscopic healing in patients with inflammatory bowel disease. Methods This was a cross-sectional study including 66 patients receiving maintenance therapy with ADA for Crohn's disease or ulcerative colitis. ADA levels and anti-adalimumab antibodies (AAA) were measured at the time of colonoscopy. The primary outcome was histologic healing (lack of endoscopic and histologic inflammation) and the secondary outcomes were endoscopic healing and serum levels of C-reactive protein, tumor necrosis factor, ICAM, VCAM, and interleukins 1β, 6, and 8. Results Sixty-six patients (59 with Crohn's disease) were included. Mean random ADA levels were significantly lower in patients with histologic and endoscopic inflammation (9.2 [SD: 8.4] versus 14.1 [6.4] μg/mL, P = 0.03 and 8.5 [SD: 7.8] versus 13.3 [SD: 7.7], P = 0.02, respectively). The ADA level that was best associated with histologic healing was 7.8 μg/mL (receiver operating characteristic: 0.76 [P = 0.04]), whereas the ADA level that was best associated with endoscopic healing was 7.5 μg/mL (receiver operating characteristic: 0.73 [P = 0.02]). The presence of AAA was associated with lower random ADA levels (5.7 versus 12.5 μg/mL, P = 0.002) and higher C-reactive protein levels (30.3 versus 12.0, P = 0.01). Conclusions Achievement of histologic and endoscopic healing may require higher levels of ADA than previously described for endoscopic remission. The measurement of random ADA levels and anti-drug antibodies may guide therapy and edify the course of incomplete responses.

For medically refractory or obstructive Crohn’s disease (CD), ostomy surgery remains an important therapeutic option. Outcomes and complications of this approach have not been well described in the era of biological therapies. Our study aims to characterize CD patients undergoing ostomy creation and assess outcome predictors. We performed a retrospective chart review of CD patients who underwent ostomy creation in our center from 2011 to 2014. Data collected include patient demographics, detailed disease- and surgery-related variables, and clinical outcomes after 26 weeks of follow-up. Of the 112 patients, 54 % were female, the median age was 39 years (range 19–78), the median disease duration was 13 years (range 0–50), 54 % had ileo-colonic disease, 55 % had stricturing phenotype, and 59 % had perianal disease. Sixty-two percent received end ostomies, and 38 % received loop ostomies. The leading indications for surgery were stricturing, fistulizing, and perianal disease (35 %). Forty-three (38 %) patients had 76 major complications, including dehydration (22 cases), intra-abdominal infection (16), and obstruction (14). Increased major postoperative complications correlated with penetrating disease (p = 0.02, odds ratio [OR] = 5.52, 95 % confidence interval [CI] = 1.25–24.42), the use of narcotics before surgery (p = 0.04, OR = 2.54, 95 % CI = 1.02–6.34), and loop ostomies (p = 0.004, OR = 4.2, 95 % CI = 1.57–11.23). Penetrating phenotype, the use of narcotics before surgery, and loop ostomies are associated with major complications in CD patients undergoing ostomy creation. These findings may influence risk management of CD patients needing ostomies.

Objective The aim of this study was to assess the correlation between serum and intestinal anti-tumour necrosis factor (TNF) levels, and their relationship to endoscopic disease activity and levels of TNF. Design Cross-sectional study of 30 patients receiving treatment with infliximab or adalimumab for Crohn9s disease or UC. For each patient, a sample of serum was matched to tissue biopsies. Endoscopic and histological disease activity was recorded for each tissue sample. Results There was a significant positive correlation between anti-TNF in serum and tissue (r=0.3920, p=0.002), especially in uninflamed tissue (r=0.50, p Conclusions Our data suggest that local tissue inflammation characterised by high levels of TNF serves as a sink for anti-TNF. We further postulate that some patients with high serum anti-TNF levels have active disease because tissue levels of anti-TNF are insufficient to neutralise local TNF production.

Clostridium difficile is the most commonly isolated stool pathogen in inflammatory bowel disease (IBD). Traditional risk factors for C. difficile may not exist in patients with IBD, and no prior studies have assessed the risk factors for the isolation of C. difficile in both symptomatic and asymptomatic IBD outpatients. We prospectively recruited consecutive IBD patients presenting to our outpatient clinic between April 2015 and February 2016. We excluded patients with a diverting ostomy or ileoanal pouch. Demographics, healthcare exposures, medical therapies and disease activity were recorded from medical charts or surveys. A rectal swab was performed from which toxigenic culture and PCR analysis for the presence of toxin and fluorescent PCR ribotyping were performed. The primary outcome of interest was isolation of toxigenic C. difficile. A total of 190 patients were enrolled in this prospective study including 137 (72%) with Crohn’s disease and 53 (28%) with ulcerative colitis. At the time of enrollment, 69 (36%) had clinically active disease. Sixteen (8.4%) patients had toxigenic C. difficile isolated on rectal swab at enrollment and four (2.1%) patients had non-toxigenic C. difficile cultured. Mixed infection with more than one toxigenic isolate was present in 5/16 (33.3%) individuals. Patients with CD with a toxin positive isolate were more likely to have a history of CDI in the past 12 months (40 vs. 11.02%, p = 0.027) and an emergency department visit in the past 12 weeks (50 vs. 20.63%, p = 0.048). In UC, individuals with isolation of C. difficile were more likely to be hospitalized within the past 12 months (66.6 vs. 8.51%, p = 0.003). C. difficile isolation at the time of presentation was not associated with a subsequent disease relapse over a 6-month period in CD (p = 0.557) or UC (p = 0.131). Healthcare exposures remain a significant risk factor for C. difficile isolation in the IBD population; however, this was not associated with relapse of disease. Further studies assessing the clinical significance of C. difficile isolation is warranted in IBD.

Background IV ciclosporin therapy is effective in steroid-refractory ulcerative colitis. The optimal drug level to achieve response and minimize complications during induction therapy is not known. Aim The primary aim was to evaluate if serum ciclosporin drug levels are associated with increased risk of colectomy within 90 days of hospitalization. Secondary aims were to determine if ciclosporin levels are associated with avoidance of colectomy at 7 and 30 days, if ciclosporin levels are associated with drug-related and postoperative complications, and if patient-specific factors are associated with response to ciclosporin. Methods We conducted a retrospective analysis of 81 hospitalized patients with steroid-refractory ulcerative colitis treated with ciclosporin. Risk factors for colectomy within 7, 30, and 90 days, medication-specific and postoperative complications were compared by first, mean, and peak ciclosporin level during IV induction therapy. Results There were 47 patients (58%) who underwent surgery. There were no differences between initial, mean, and peak ciclosporin levels among responders and nonresponders and treatment-related or postoperative complications. Responders within 90 days had lower C-reactive-protein levels (20mg/L vs. 38mg/L, P = 0.01), lower serum albumin concentrations (3.4g/dL vs. 3.7g/dL, P = 0.03), and higher rates of kidney injury (50% vs 17%, P = 0.002). Conclusion Initial, mean, and peak serum levels of ciclosporin did not correlate with response or toxicity. However, C-reactive-protein levels levels and kidney injury may be helpful in predicting clinical response to ciclosporin.

Goals The aim of this study was to assess whether sustained 6-thioguaninenucleotide (6-TGN) levels were associated with improved long-term outcomes in patients with inflammatory bowel diseases (IBD). Background Cross-sectional data have shown that thiopurine metabolites are correlated with clinical efficacy in patient receiving thiopurines for IBD but the role for serial measurements through treatment course is unclear. Study We conducted a retrospective cohort study including patients with IBD on thiopurine monotherapy and had serial 6-TGN levels measured. Predictive variables included demographics, disease phenotype, 6-TGN levels (nadir, median, and peak levels). The primary outcome was the development of a disease relapse. The secondary outcome was the need for IBD surgery. Results Two hundred eighteen 6-TGN samples from 87 patients were analyzed. Nadir and median 6-TGN levels were significantly higher in patients who did not relapse [185 and 233 pmol per 8×10 red blood cells (RBCs)] as compared with levels in patients who did relapse (150 and 167 pmol per 8×10 RBCs, P=0.025) but there was no significant difference in peak 6-TGN level. When adjusted for confounding factors, a nadir 6-TGN level ≥161 and a median 6-TGN level ≥264 were associated with a significant decrease in the rate of disease exacerbation (hazard ratio: 0.5; 95% confidence interval, 0.26-0.87; P=0.016 and hazard ratio: 0.4; 95% confidence interval, 0.2-0.82; P=0.14). Conclusions Serial thiopurine metabolite level assessments and dose adjustment aiming to maintain higher 6-TGN levels may be helpful to improve long-term outcomes in patients with IBD.

Background Disease location, behavior, and average activity over time vary significantly amongst patients with inflammatory bowel disease (IBD). Despite this heterogeneity patients are often subjected to a “one size fits all” treatment plan. Clinical and multi-omic profiles which predict responsiveness to treatment are needed given the expanding range of therapeutic options for IBD. Methods The Study of Prospective Adult Research Cohort of IBD (SPARC IBD) is a prospective, longitudinal cohort study of patients with IBD ages 18 and older managed according to local standards at 17 academic medical centers in the US. Demographic data, disease-related data, and patient-reported outcomes are collected at baseline, during routine GI office visits, and quarterly by data abstraction from the electronic health record, patient surveys, and highly structured electronic case report forms (eCRF) created with Epic Systems (IBD SmartForm). Biosamples are collected at baseline (blood and stool), at the time colonoscopy (stool and tissue), and after key medication changes (blood and stool). Clinical data is transferred from sites on a periodic basis and stored in the Crohn’s & Colitis Foundation’s exchange platform called IBD Plexus. A portion of the biosamples are analyzed and the rest are banked for future use. Results Between November 2016 and October 2019, 2582 patients have enrolled in SPARC IBD (66% Crohn’s disease [CD], 33% ulcerative colitis (UC), and 1% IBD-U). Females comprise 52.5% of the cohort. Median age at enrollment is 37 years (range18-85). The majority of patients are white (80.5%) and non-Hispanic or Latino (84.5%). Median disease duration is 12 years (range 0–53). Distribution of disease location in the CD sub-group is 44% with small bowel and colonic disease, 28% with isolated small bowel disease, and 15% with isolated colonic disease. In the UC sub-group, 50.5% of patients have extensive colitis, followed by 23.5% with left-sided colitis, and 8.8% with proctitis. Among CD patients, 17.6% have stricturing disease, 12.5% have penetrating disease, 5.8% have both stricturing and penetrating disease and 16.2% have perianal involvement. At time of study enrollment 60% of CD patients, 41% of UC patients and 37% of IBD-U patients were on a biologic. The majority of patients with CD (88%) and UC (89%) were in remission. Conclusions SPARC IBD is a prospective cohort study of adult IBD patients which combines high-resolution phenotyping with biosample collection at multiple points in time. The unique aspects of this study including the multiple modalities for clinical data collection, the geographic diversity of patients enrolled, as well as the biosample procurement at multiple time points position SPARC IBD to aid in the discovery of novel biomarkers which can predict therapeutic responsiveness.

Introduction Vedolizumab (VDZ), a gut-selective antibody that binds specifically to integrin α4β7, is approved for treatment of adults with moderate-to-severe ulcerative colitis (UC). An association between VDZ levels and clinical remission during induction therapy at Week (Wk) 6 was observed in pivotal trial data; the majority of nonresponders at Wk 6 had VDZ levels 0.14 L/d had reduced efficacy outcomes (Osterman MT, et al. Aliment Pharmacol Ther. 2019). In the ongoing randomized controlled trial (ENTERPRET), we are evaluating whether dose escalation starting at Wk 6 in clinical nonresponders with high VDZ clearance (level Methods Adults with moderately to severely active UC received VDZ 300 mg IV on Day 1 and Wk 2. At Wk 5, VDZ concentration in serum was measured; clinical response was assessed at Wk 6 based on partial Mayo score (reduction in partial Mayo score ≥2 points and ≥25% from baseline [Day 1] with an accompanying decrease in rectal bleeding subscore ≥1 point or absolute rectal bleeding score ≤1 point). Descriptive analysis was used for these interim data, including baseline characteristics in responder and nonresponder groups. Results A total of 117 patients (mean age 41.2 years, 40.2% female) were analyzed; 112 were classified as a responder (n=55) or nonresponder (n=57) based on Wk 6 response. At baseline, mean disease duration was higher in nonresponders than responders (9.5 vs 7.1 years), with 47.4% of nonresponders having disease duration ≥7 years compared with 38.2% of responders. Endoscopic activity score was higher in nonresponders vs responders (49.1% vs 36.4% had severely active disease [Mayo endoscopic subscore=3]). 63.2% of nonresponders had a high stool frequency at baseline (Mayo subscore=3) compared with 49.1% of responders. 63.6% of responders had more severe rectal bleeding scores (Mayo subscore of 2–3) compared with 45.6% of nonresponders. More responders (67.3%) were anti-TNF–naïve at baseline than nonresponders (52.6%). At Wk 6, change in mean (SD) partial Mayo score from baseline was -4.2 (1.65) for responders and -0.2 (0.96) for nonresponders. Wk 5 mean VDZ serum concentrations were numerically lower in nonresponders (31.5 [SD=12.8] vs 40.3 [SD=15.3] μg/mL in responders). There were no unexpected treatment-emergent adverse events in either group. Conclusion Interim data from ENTERPRET show Wk 6 responders had higher VDZ serum concentrations at Wk 5 than nonresponders. Although current results are consistent with the hypothesis that lower response to VDZ at Wk 6 correlates with lower drug exposure, we await the final results of ENTERPRET to better understand the exposure-response relationship of VDZ.

Patients with inflammatory bowel diseases (IBDs) may present with several hepatic abnormalities. Some of these liver diseases are benign and only require observation, whereas others may cause liver failure and require liver transplantation. The aim of this review was to present and summarize the latest evidence on the most common liver diseases seen in patients with IBD. These manifestations can be divided in to 3 groups: those that are seen in association with IBD, those that are due to metabolic and physiologic changes induced by the IBD and those that are secondary to the drugs used in the treatment of IBD. Primary sclerosing cholangitis is one of the most common hepatobiliary manifestations of IBD that is more prevalent in patients with ulcerative colitis. There is no approved medical treatment for primary sclerosing cholangitis and about 50% of patients will require liver transplantation within 10 to 15 years from the time of diagnosis. Among the drugs that are commonly used in the treatment of IBD, thiopurines and methotrexate impose the higher risk of hepatotoxicity. In most cases, dose adjustment and avoidance of hepatotoxins will normalize the liver tests and discontinuation of the drug is required in a minority of cases. Reactivation of hepatitis B virus during immunosuppressive therapy is a major concern and adequate screening and vaccination is warranted. The approach to a patient with IBD who presents with abnormal liver chemistries can be challenging not only because 2 or more conditions can co-exist but also because management must be individualized.

Summary Background Studies have found that depression is more frequent in patients with inflammatory bowel disease (IBD) than the general population. Clinicians are now trying to pinpoint risk factors for psychological impairment in the IBD population. Aims To examine the demographic and phenotypic variables associated with the development of depression among a diverse cohort of IBD patients. We also sought to describe psychotropic therapy prescribed to IBD patients. Methods We conducted a retrospective cohort study including patients with Crohn's disease (CD) and ulcerative colitis (UC) without a prior psychiatric diagnosis and followed in the gastroenterology clinics of the private university hospital and public safety net hospital at a large academic centre in Miami (Florida). Predictive variables included demographic characteristics, IBD phenotype, exposure to IBD medications, history of a surgical stoma or seton placement, extra-intestinal manifestations, laboratory indices, aggressive disease and disease activity (based on imaging and endoscopic parameters). Proportional hazard regression models and stepwise Cox regression analysis were used for statistical analysis. Results Independent predictors of depression were female gender [HR: 1.3 (95% CI: 1.1–1.7), P = 0.01], aggressive disease [HR: 1.4 (95% CI: 1.02–1.9), P = 0.03] and active disease [HR: 1.5 (95% CI: 1.1–2.0), P = 0.04]. In the group that did develop a depressive disorder, 65% received pharmacologic therapy with one or more psychotropic agents. Conclusions We found female gender, aggressive disease and increased endoscopic/radiological activity to be independently associated with the development of depression in inflammatory bowel disease.

Inflammatory bowel diseases are chronic conditions that frequently affect patients during their childbearing years. Considering the characteristics of disease and the medications used to treat it, several issues arise in the care of these patients when they attempt or achieve conception. We review the most current evidence concerning fertility and pregnancy outcomes in patients with inflammatory bowel diseases. With the exception of those women who undergo pelvic surgery, patients with inflammatory bowel diseases have no decreased fertility. Sulfasalazine decreases fertility in men. When looking at obstetrical outcomes, active disease at conception is associated with an increased risk of preterm delivery and low birth weight. While most medications used to treat inflammatory bowel diseases are low risk, some precautions need to be taken and the risk-to-benefit ratio needs to be considered on an individualized basis. In general, aminosalicylates and thiopurines should be continued, but methotrexate is contraindicated. Anti-tumour necrosis factor agents are considered safe to continue but full monoclonal antibodies do cross the placenta. As a general rule, the it is important to counsel women that conception is optimal when disease is in remission, as adverse obstetrical outcomes are directly associated with disease activity. Clinicians need to educate patients before, during and after conception, emphasizing treatment compliance.

Whether the prevalence of thyroid cancer is different in thyroid glands with a single nodule (SN) versus multinodular goiter (MNG) remains uncertain. Therefore, a meta-analysis was performed to evaluate the extant literature on the comparative prevalence of thyroid cancer in SN compared with MNG.We searched MEDLINE, EMBASE, Scopus, Cochrane Central, and reference list for selected observational, cross-sectional, and longitudinal studies evaluating thyroid cancer in SN and MNG. Toxic nodules were not included in the analysis. Two reviewers working independently extracted descriptive, methodological and outcome data from each study with consensus resolution of discrepancies. Meta-analytic estimates of treatment effects were generated using a random-effect model.Fourteen studies encompassing 23565 patients with MNG and 20723 patients with SN were eligible for inclusion. Most eligible studies were at a moderate risk of bias. MNGs were associated with a lower risk of thyroid cancer than SN (pooled odds ratio 0.8 [95% confidence interval 0.67-0.96]; I(2)=35%). Subgroup analysis suggested that this difference depends on the inclusion of studies conducted outside the United States (odds ratio 0.71 [95% confidence interval 0.60-0.83]; I(2)=11%).Thyroid cancer may be less frequent in MNG compared to SN, particularly outside the United States and perhaps in iodine-deficient areas.

Surgery for inflammatory bowel disease (IBD) is common and represents a large portion of the cost of IBD treatment. There are multiple risk factors for post-operative complications after IBD surgery, but the role of ethnicity remains unclear. The aim of our study was to compare the rate of post-operative complications in Hispanic and non-Hispanic patients with equal access to health care. We designed a case–control study including patients enrolled in a health plan available to uninsured patients at Jackson Memorial Hospital (Miami, FL, USA) who had access to health care for at least 24 consecutive months prior to surgery. Sixty-seven Hispanic patients (cases) and 75 non-Hispanic patients (controls) met criteria and were compared with respect to demographics, type of surgery, disease phenotype, and laboratory markers. Primary outcome was the development of a medical or surgical complication. A slight numerical increase in post-operative complications was seen in Hispanic patients; this did not reach statistical significance [1.06 (95 % CI 0.48–2.36; p = 0.88)]. Factors independently associated with post-operative complications included diagnosis of ulcerative colitis [OR 5.4 (95 % CI 1.67–20.58; p = 0.004)], pre-operative albumin levels

Patients with inflammatory bowel disease (IBD) present with several extraintestinal manifestations, including systemic inflammation and hypercoagulability. Limited studies have shown that patients with IBD may have a higher risk of developing atherosclerosis. The incidence of coronary artery disease (CAD) and the role of traditional CAD risk factors in IBD patients remain unclear. We sought to compare the rates of CAD events in patients with IBD with matched controls.We performed a longitudinal cohort study of patients with IBD compared with matched controls. The primary outcome was the development of CAD events. Traditional and nontraditional CAD risk factors were assessed. Cox proportional hazards model was used to assess the impact of each CAD risk factor on the outcomes.A total of 356 IBD patients and 712 matched controls were followed for a median of 53 and 51 months, respectively. The unadjusted hazard ratio (HR) for developing CAD in the IBD group was 2.85 (95% confidence interval (CI) 1.82-4.46). IBD patients had significantly lower rates of selected traditional CAD risk factors (hypertension, diabetes, dyslipidemia, and obesity; P0.01 for all). Adjusting for these factors, the HR for developing CAD between groups was 4.08 (95% CI 2.49-6.70). Among nontraditional risk factors, an elevated white blood cell (WBC) count was a risk factor for CAD development in the IBD group (HR 1.23; 95% CI 1.15-1.33).An increased incidence of CAD events was noted in IBD patients despite having a lower burden of traditional risk factors. Additionally, these risk factors had a lower impact on CAD development in the IBD group. Further investigation into how nontraditional risk factors, including WBC count, and the effect of attenuating systemic inflammation in IBD patients change CAD risk is warranted.