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Background: Vedolizumab has since 2021 been available as a subcutaneous formulation. We aimed to assess 18-month drug persistence and possible predictive factors associated with discontinuation, safety, serum drug profile, drug dosing, and disease activity in a real-world cohort of patients with inflammatory bowel disease switched from intravenous to subcutaneous vedolizumab maintenance treatment., Methods: Eligible patients were switched to subcutaneous vedolizumab and followed for 18 months or until discontinuation of subcutaneous treatment. Data on preferred route of administration, adverse events, drug dosing, serum-vedolizumab, disease activity, fecal calprotectin, and C-reactive protein were collected. Persistence was described using Kaplan-Meier analysis. The impact of clinical and biochemical variables on persistence was analyzed with Cox proportional hazard models., Results: We included 108 patients, and the estimated 18-month drug persistence was 73.6% (95% CI [64.2-80.1]). Patients in clinical remission at switch were less likely to discontinue SC treatment (HR = 0.34, 95% CI [0.16-0.73], P  = .006), and patients favoring intravenous treatment at switch were almost 3 times more likely to discontinue (HR = 2.78, 95% CI [1.31-5.90], P  = .008). Four patients discontinued subcutaneous vedolizumab due to injection site reactions. At 18 months, 88% of patients administered subcutaneous vedolizumab with an interval of ≥ 14 days, and serum-vedolizumab was 39.1 mg/L. Disease activity was stable during follow-up., Conclusions: Three of the four patients remained on subcutaneous vedolizumab after 18 months, a large proportion received treatment at standard dosing intervals, and disease activity remained stable. This indicates that switching from intravenous to subcutaneous vedolizumab treatment is convenient and safe., Competing Interests: T.H.W. and K.A. report consultant fees from Takeda outside the submitted work. A.W.M. reports research grant from Takeda. B.M. reports consultant fees from Takeda, Janssen, AbbVie, Pfizer; advisory board Takeda, Janssen, AbbVie, Pfizer, Sandoz, Pharma Cosmos; speaker fees from Takeda, Janssen, AbbVie, Sandoz, Orion Pharma. M.L.H. reports speaker fees from AbbVie, Meda, Tillotts, and Takeda; advisory board Takeda. M.H., L.B., N.B., and D.J.W. report no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background & Aims: Few patients with primary sclerosing cholangitis (PSC) and inflammatory bowel diseases (IBDs) are exposed to tumor necrosis factor (TNF) antagonists because of the often mild symptoms of IBD. We assessed the effects of anti-TNF agents on liver function in patients with PSC and IBD, and their efficacy in treatment of IBD., Methods: We performed a retrospective analysis of 141 patients with PSC and IBD receiving treatment with anti-TNF agents (infliximab or adalimumab) at 20 sites (mostly tertiary-care centers) in Europe and North America. We collected data on the serum level of alkaline phosphatase (ALP). IBD response was defined as either endoscopic response or, if no endoscopic data were available, clinical response, as determined by the treating clinician or measurements of fecal calprotectin. Remission was defined more stringently as endoscopic mucosal healing. We used linear regression analysis to identify factors associated significantly with level of ALP during anti-TNF therapy., Results: Anti-TNF treatment produced a response of IBD in 48% of patients and remission of IBD in 23%. There was no difference in PSC symptom frequency before or after drug exposure. The most common reasons for anti-TNF discontinuation were primary nonresponse of IBD (17%) and side effects (18%). At 3 months, infliximab-treated patients had a median reduction in serum level of ALP of 4% (interquartile range, reduction of 25% to increase of 19%) compared with a median 15% reduction in ALP in adalimumab-treated patients (interquartile range, reduction of 29% to reduction of 4%; P = .035). Factors associated with lower ALP were normal ALP at baseline (P < .01), treatment with adalimumab (P = .090), and treatment in Europe (P = .083)., Conclusions: In a retrospective analysis of 141 patients with PSC and IBD, anti-TNF agents were moderately effective and were not associated with exacerbation of PSC symptoms or specific side effects. Prospective studies are needed to investigate the association between use of adalimumab and reduced serum levels of ALP further., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Patients with inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, are at increased risk for colorectal cancer (CRC). Analyses of DNA methylation patterns in stool samples have been reported to detect CRC in patients with IBD. We sought to validate these findings in larger cohorts and assess the accuracy of analysis of DNA methylation patterns in stool for detection of CRC and high-grade dysplasia (HGD) normalized to methylation level at ZDHHC1., Methods: We obtained buffered, frozen stool samples from a US case-control study and from 2 European surveillance cohorts (referral or population based) of patients with chronic ulcerative colitis (n = 248), Crohn's disease (n = 82), indeterminate colitis (n = 2), or IBD with primary sclerosing cholangitis (n = 38). Stool samples were collected before bowel preparation for colonoscopy or at least 1 week after colonoscopy. Among the study samples, stools from individuals with IBD but without neoplasia were used as controls (n = 291). DNA was isolated from stool, exposed to bisulfite, and then assayed by multiplex quantitative allele-specific real-time target and signal amplification. We analyzed methylation levels of BMP3, NDRG4, VAV3, and SFMBT2 relative to the methylation level of ZDHHC1, and compared these between patients with CRC or HGD and controls., Results: Levels of methylation at BMP3 and VAV3, relative to ZDHHC1 methylation, identified patients with CRC and HGD with an area under the curve value of 0.91 (95% CI, 0.77-1.00). Methylation levels at specific promotor regions of these genes identified 11 of the 12 patients with CRC and HGD, with 92% sensitivity (95% CI, 60%-100%) and 90% specificity (95% CI, 86%-93%). The proportion of false-positive results did not differ significantly among the case-control, referral cohort, and population cohort studies (P = .60) when the 90% specificity cut-off from the whole sample set was applied., Conclusions: In an analysis of stool samples from 3 independent studies of 332 patients with IBD, we associated levels of methylation at 2 genes (BMP3 and VAV3), relative to level of methylation at ZDHHC1, with detection of CRC and HGD. These methylation patterns identified patients with CRC and HGD with more than 90% specificity, and might be used in CRC surveillance., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Aim: To evaluate the use of chromoendoscopy for surveillance of ulcerative colitis in a real-life community hospital setting., Methods: Patients with extensive ulcerative colitis, having disease duration of more than 8 years and who presented between the years of 1999 to 2013, were offered enrolment in this single cohort prospective study. All participants underwent standard bowel preparation with sodium phosphate and chromoendoscopy. Two expert endoscopists, novice to chromoendoscopy, evaluated each segment of the colon with standard-definition colonoscopes after spray application of 0.4% indigo carmine. All observed lesions were recorded and evaluated before being removed and/or biopsied. In addition, nontargeted biopsies were taken from each segment of the colon. The dysplasia detection rate and dysplasia detection yield were ascertained., Results: A total of 21 neoplastic lesions (2 carcinomas, 4 of high-grade dysplasia and 15 of low-grade dysplasia) and 27 nondysplastic lesions were detected in 16 of the total 67 patients (70% male; median disease duration: 17 years; median age at diagnosis: 25 years; 92% aminosalicylate-treated). The dysplasia detection rate was 10.5% (7/67 patients). The dysplasia detection yield was 20.8% (10/48) for targeted biopsies and 3.5% (11/318) for nontargeted biopsies. The sensitivity and specificity for the macroscopic evaluation of neoplasia using chromoendoscopy were 48% [95% confidence interval (CI): 26%-70%] and 96% (95%CI: 93%-98%), respectively. The positive predictive and negative predictive values were 42% (95%CI: 27%-59%) and 97% (95%CI: 95%-98%), respectively. A total of 19/21 dysplastic lesions were detected in mucosa with histologic inflammation., Conclusion: Chromoendoscopy seems to be of value for dysplasia surveillance of ulcerative colitis in a community hospital setting. The yield of non-targeted biopsies is negligible., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest.

Ulcerative colitis (UC) is characterized by chronic inflammation of the large bowel in genetically susceptible individuals exposed to environmental risk factors. The disease course can be difficult to predict, with symptoms ranging from mild to severe. There is no generally accepted definition of severe UC, and no single outcome is sufficient to classify a disease course as severe. There are several outcomes indicating a severe disease course, including progression of the disease's extension, a high relapse rate, the development of acute severe colitis, colectomy, the occurrence of colorectal cancer and UC-related mortality. When evaluating a patient's prognosis, it is helpful to do so in relation to these outcomes. Using these outcomes also makes it easier to isolate factors predictive of severe disease. The aims of this article are to evaluate different disease outcomes and to present predictive factors for these outcomes.

Background: Current methods to establish the diagnosis of intestinal tuberculosis are inadequate., Objectives: We aimed to determine the clinical features of intestinal tuberculosis and evaluate inflammatory biomarkers in intestinal as well as pulmonary tuberculosis., Methods: We recruited 38 intestinal tuberculosis patients, 119 pulmonary tuberculosis patients and 91 controls with functional gastrointestinal disorders between October 2009 and July 2012 for the investigation of clinical features, C-reactive protein (CRP), faecal and serum calprotectin. Faecal calprotectin ≥200 µg/g was used as a cut-off to determine intestinal inflammation of clinical significance. Three patient categories were established: (a) pulmonary tuberculosis and faecal calprotectin <200 µg/g (isolated pulmonary tuberculosis); (b) pulmonary tuberculosis and faecal calprotectin ≥200 µg/g (combined pulmonary and intestinal tuberculosis); (c) isolated intestinal tuberculosis., Results: Common clinical features of intestinal tuberculosis were abdominal pain, fatigue, weight loss and watery diarrhoea. Intestinal tuberculosis patients had elevated median CRP (10.7 mg/l), faecal calprotectin (320 µg/g) and serum calprotectin (5.7 µg/ml). Complete normalisation of CRP (1.0 mg/L), faecal calprotectin (16 µg/g) and serum calprotectin (1.4 µg/ml)) was seen upon clinical remission. Patients with combined pulmonary and intestinal tuberculosis had the highest levels of CRP (53.8 mg/l) and serum calprotectin (6.5 µg/ml) and presented with signs of more severe disease., Conclusion: Calprotectin analysis reveals intestinal tuberculosis in patients with pulmonary tuberculosis and pinpoints those in need of rigorous follow-up.

Aim: To investigate whether routinely measured clinical variables could aid in differentiating intestinal tuberculosis (ITB) from Crohn's disease (CD)., Methods: ITB and CD patients were prospectively included at four South Indian medical centres from October 2009 to July 2012. Routine investigations included case history, physical examination, blood biochemistry, ileocolonoscopy and histopathological examination of biopsies. Patients were followed-up after 2 and 6 mo of treatment. The diagnosis of ITB or CD was re-evaluated after 2 mo of antituberculous chemotherapy or immune suppressive therapy respectively, based on improvement in signs, symptoms and laboratory variables. This study was considered to be an exploratory analysis. Clinical, endoscopic and histopathological features recorded at the time of inclusion were subject to univariate analyses. Disease variables with sufficient number of recordings and P < 0.05 were entered into logistic regression models, adjusted for known confounders. Finally, we calculated the odds ratios with respective confidence intervals for variables associated with either ITB or CD., Results: This study included 38 ITB and 37 CD patients. Overall, ITB patients had the lowest body mass index (19.6 vs 22.7, P = 0.01) and more commonly reported weight loss (73% vs 38%, P < 0.01), watery diarrhoea (64% vs 33%, P = 0.01) and rural domicile (58% vs 35%, P < 0.05). Endoscopy typically showed mucosal nodularity (17/31 vs 2/37, P < 0.01) and histopathology more frequently showed granulomas (10/30 vs 2/35, P < 0.01). The CD patients more frequently reported malaise (87% vs 64%, P = 0.03), nausea (84% vs 56%, P = 0.01), pain in the right lower abdominal quadrant on examination (90% vs 54%, P < 0.01) and urban domicile (65% vs 42%, P < 0.05). In CD, endoscopy typically showed involvement of multiple intestinal segments (27/37 vs 9/31, P < 0.01). Using logistic regression analysis we found weight loss and nodularity of the mucosa were independently associated with ITB, with adjusted odds ratios of 8.6 (95%CI: 2.1-35.6) and 18.9 (95%CI: 3.5-102.8) respectively. Right lower abdominal quadrant pain on examination and involvement of ≥ 3 intestinal segments were independently associated with CD with adjusted odds ratios of 10.1 (95%CI: 2.0-51.3) and 5.9 (95%CI: 1.7-20.6), respectively., Conclusion: Weight loss and mucosal nodularity were associated with ITB. Abdominal pain and excessive intestinal involvement were associated with CD. ITB and CD were equally common.

The authors review the clinical outcome in patients with Crohn's disease (CD) based on studies describing the natural course of the disease. Population-based studies have demonstrated that the incidence rates and prevalence rates for CD have increased since the mid-1970s. The authors search for English language articles from 1980 until 2011. Geographical variations, incidence, prevalence, smoking habits, sex, mortality and medications are investigated. An increasing incidence and prevalence of CD have been found over the last three decades. The disease seems to be most common in northern Europe and North America, but is probably increasing also in Asia and Africa. Smoking is associated with an increased risk of developing CD. Age < 40 at diagnosis, penetrating/stricturing complications, need for systemic steroids, and disease location in terminal ileum are factors associated with higher relapse rates. A slight predominance of women diagnosed with CD has been found. Ileocecal resection is the most commonly performed surgical procedure, and within the first five years after the diagnosis about one third of the patients have had intestinal surgery. Smoking is associated with a worse clinical course and with increased risk of flare-ups. In most studies the overall mortality is comparable to the background population. To date, the most effective treatment options in acute flares are glucocorticosteroids and tumor necrosis factor (TNF)-α-blockers. Azathioprine/methotrexate and TNF-α-blockers are effective in maintaining remission.

Background: Fatigue is reported to reduce health-related quality of life (HRQOL) in chronic diseases. Studies on the importance of fatigue and its implications for the patient's HRQOL in inflammatory bowel disease (IBD) remain scarce and need to be explored., Aim: To investigate the influence of chronic fatigue on both generic and disease-specific HRQOL in IBD., Methods: Patients in remission, with mild and moderate IBD completed the Fatigue Questionnaire, the Short-Form 36 (SF-36) and the Norwegian version of the Inflammatory Bowel Disease Questionnaire (N-IBDQ). In addition, demographic and clinical variables were obtained., Results: In total, 140 patients were included; the mean age of patients with chronic fatigue was 44.2 years (s.d. = 15.8), that of nonfatigued was 44.7 years (s.d. = 16.0). Ulcerative colitis (UC)/Crohn's disease (CD) = 92/48. Chronic fatigue was associated, after controlling for covariates, with a reduction of HRQOL scores in 6/8 SF-36 dimensions in UC and 5/8 dimensions in CD. In N-IBDQ, chronic fatigue was associated with a reduction of HRQOL in four subdimensions and total score in CD and all dimensions in UC., Conclusions: Fatigue is associated with reduction of HRQOL scores in IBD. The physical HRQOL domains are particularly affected. The impact of fatigue on disability, sick leave, school and work attendance has to be studied further., (© 2010 Blackwell Publishing Ltd.)

Background and Aims: Mucosal healing (MH) in inflammatory bowel disease may be an important sign of efficacy of treatment and a prognostic marker of long-term disease. The aim of the study was to examine both the possible predictors of mucosal healing and the impact of healing on subsequent course of disease., Methods: In 740 incident patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) between 1990 and 1994 (before biologic therapy was available), demographics and symptoms were recorded. Clinical and endoscopic evaluations were done at baseline before treatment and repeated after 1 and 5 years in 495 patients., Results: In UC patients, education longer than 12 years and extensive disease at diagnosis were significant predictors of MH after 1 year (adjusted P = .004 and P = .02, respectively). MH was significantly associated with a low risk of future colectomy (P = .02). In patients with CD, fever at diagnosis and medical treatment without steroids were significant predictors for MH (adjusted P = .03 and P = .01, respectively). MH was significantly associated with less inflammation after 5 years (P = .02), decreased future steroid treatment (P = .02)., Conclusions: Several factors predicted subsequent MH. Education as predictor may implicate the importance of coping, compliance, or lifestyle. MH after 1 year of treatment is predictive of reduced subsequent disease activity and decreased need for active treatment. The present results give further strength to the use of mucosal healing as a clinical indicator and treatment goal in inflammatory bowel disease.