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Purpose: Uveitis is one of the ocular manifestations of inflammatory bowel disease (IBD) that is often overlooked and has been considered a sign of severe IBD. As typical subtypes of IBD, differences exist in the prevalence of uveitis between Crohn's disease (CD) and ulcerative colitis (UC). Our study systematically assessed differences in the prevalence of uveitis between CD and UC. Methods: The Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) guidelines were used. We performed a systematic review of published literature from PubMed and Embase on 30 March 2022. Two investigators independently selected studies, extracted data and evaluated methodological quality. Either a fixed‐ or a random‐effects model was used to calculate the risk ratio (RR), odds ratio (OR) and 95% confidence interval (95% CI) depending on the heterogeneity of studies. Sensitivity analysis was used to examine the heterogeneity by removing article by article, while subgroup analysis was conducted in accordance with various regions. Results: Our study included data from 14 studies encompassing 115 854 participants. The prevalence of uveitis in IBD was estimated to be 2.38% (95% CI 1.60%–3.17%). The prevalence of uveitis in CD (3.27%, 95% CI 2.15%–4.39%) was significantly higher than in UC (1.60%, 95% CI 0.93%–2.27%; RR 1.76, 95% CI 1.39–2.22, p < 0.05). In subgroup analysis, a higher incidence of CD combined with uveitis was also observed in IBD patients residing in Europe (RR 1.75, 95% CI 1.37–2.24). Conclusions: Data from 115 854 IBD patients showed that CD patients were more likely to suffer from uveitis than UC patients. Ocular manifestations in IBD, particularly CD, warrant greater attention. [ABSTRACT FROM AUTHOR]

An estimated 2.5–3 million individuals (0.4%) in Europe are affected by inflammatory bowel disease (IBD). Whilst incidence rates for IBD are stabilising across Europe, the prevalence is rising and subsequently resulting in a significant cost to the healthcare system of an estimated 4.6–5.6 billion euros per year. Hospitalisation and surgical resection rates are generally on a downward trend, which is contrary to the rising cost of novel medication. This signifies a large part of healthcare cost and burden. Despite publicly funded healthcare systems in most European countries, there is still wide variation in how patients receive and/or pay for biologic medication. This review will provide an overview and discuss the different healthcare systems within Western Europe and the barriers that affect overall management of a changing IBD landscape, including differences to hospitalisation and surgical rates, access to medication and clinical trial participation and recruitment. This review will also discuss the importance of standardising IBD management to attain high-quality care for all patients with IBD. [ABSTRACT FROM AUTHOR]

Background: Vedolizumab (VDZ) for subcutaneous (SC) injection was approved for use in Europe in 2020 and the US in 2023. Promising efficacy and tolerability have been proven in pivotal trials. However, real-world data on the SC use of VDZ, especially in patients with active disease, are still lacking. We aimed to determine treatment persistence and the drug's efficacy in inflammatory bowel disease (IBD) patients with active disease in comparison to patients in clinical remission. Methods: Patients treated for IBD in a tertiary care center from July 2020 to December 2021 were included in this study. Clinical and biochemical parameters and data on treatment adherence were collected. VDZ trough levels and disease activity before and after the switch from intravenous (IV) to SC injections were monitored during routine checkups and were retrospectively analyzed. The patients were followed up until week 20. Results: Eighty-two patients were included in the study. Of them, 35 patients had active disease (35/82 = 43%) at the time of the switch and 47 patients (47/82 = 57%) were in remission. In total, 10 patients experienced switch failure, 5 were switched back to IV VDZ, and 5 were swapped to a different biologic agent. We observed an increase in VDZ trough levels from the switch to week 8 and from the switch to week 20 in the remission group. Vedolizumab trough levels of 7.4, 51.4, and 33.45 ug/mL at the switch, week 8, and week 20 were identified to discriminate between remission and disease activity in our cohort. There was no new safety signal detected during the study period. Conclusions: The switch from IV to SC VDZ proved to be efficient, safe, and even capable of reducing residual disease activity. [ABSTRACT FROM AUTHOR]

Background: The non-interventional PROPER study generated real-world evidence on clinical outcomes following transition in routine practice from reference adalimumab to the EMA-approved SB5 biosimilar adalimumab in patients with immune-mediated inflammatory disease. Methods: Adults with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), Crohn's disease (CD), or ulcerative colitis (UC) were enrolled at 63 sites across Europe. Eligible patients received ≥ 16 weeks of routine treatment with reference adalimumab before transitioning to SB5, and were followed for 48 weeks post-transition. The primary objective was to evaluate candidate predictors (clinically relevant baseline variables with incidence ≥ 15% by indication cohort) associated with persistence on SB5 at 48 weeks post-initiation. Key primary outcome measures were persistence on SB5 (estimated by Kaplan–Meier methodology) and clinical characteristics and disease activity scores at the time of transition to SB5 treatment (baseline). Results: A total of 955 eligible patients were enrolled (RA, n = 207; axSpA, n = 127; PsA, n = 162; CD, n = 447; UC, n = 12), of whom 932 (97.6%) completed follow-up and 722 (75.6%) were still receiving SB5 at week 48. Kaplan–Meier estimates (95% confidence interval, CI) of persistence on SB5 at week 48 for RA, axSpA, PsA, and CD were 0.86 (0.80–0.90), 0.80 (0.71–0.86), 0.81 (0.74–0.86), and 0.72 (0.67–0.76), respectively. The single candidate predictor associated with probability of SB5 discontinuation before week 48 was female sex [RA, axSpA, and CD cohorts; HR (95% CI): 3.53 (1.07–11.67), 2.38 (1.11–5.14), and 2.21 (1.54–3.18), respectively]. Disease activity scores remained largely unchanged throughout the study, with proportions by cohort in remission at baseline versus week 48 being 59.2% versus 57.2%, 81.0% versus 78.0%, 94.7% versus 93.7%, and 84.0% versus 85.1% for patients with RA, axSpA, PsA, and CD, respectively. Similarly, the SB5 dosing regimen remained unchanged for the majority of patients from baseline to week 48, the most common regimen being 40 mg every 2 weeks. In total, 232 patients (24.3%) reported at least one adverse drug reaction, and most events were mild; eight patients (3.9%) in the RA cohort experienced nine serious adverse events (SAEs; two possibly related to SB5); eight patients (4.9%) in the PsA cohort experienced nine SAEs (one possibly related to SB5); 22 patients (4.9%) in the CD cohort experienced 27 SAEs (four possibly related to SB5); and no SAEs were observed in the UC cohort. Conclusions: With the exception of female sex in RA, axSpA, and CD, none of the candidate predictors were associated with SB5 discontinuation. Persistence on SB5 was high, treatment effectiveness was maintained, and no safety signals were detected. Trial Registration: This trial is registered with ClinicalTrials.gov: NCT04089514. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) comprises a spectrum of chronic immune-mediated diseases that affect the gastrointestinal tract. Onset typically occurs in early adulthood. The incidence of this disease has increased worldwide. Its prevalence has increased in Colombia and occurs predominantly in women. Considering that this disease is not curable, the main objective of management is to achieve remission. Many women are affected by IBD during different stages of their lives, including their reproductive life, pregnancy, and menopause. Because of this, the way the disease is managed in women of reproductive age can affect the course of IBD. Treatment and health maintenance strategies are very relevant; for patients with a desire to conceive, remission of the disease is very important at the time of conception and throughout the pregnancy to ensure adequate outcomes for both mother and fetus. Also, remission is necessary at least 3 months prior to conception. It is well known that active disease during conception and pregnancy is associated with adverse outcomes. In addition, active perianal disease is an indication of cesarean delivery, resulting in an increased risk of intestinal surgery and post-operative complications. [ABSTRACT FROM AUTHOR]

Background: Both inflammatory bowel disease (IBD) and hepato‐pancreato‐biliary cancers (HPBC) have been established to cause a huge socioeconomic burden. Epidemiological studies have revealed a close association between IBD and HPBC. Methods: Herein, we utilized inverse‐variance weighting to conduct a two‐sample Mendelian randomization analysis. We sought to investigate the link between various subtypes of IBD and HPBC. To ensure the accuracy and consistency of our findings, we conducted heterogeneity tests, gene pleiotropy tests, and sensitivity analyses. Results: Compared to the general population, IBD patients in Europe exhibited a 1.22‐fold increased incidence of pancreatic cancer (PC) with a 95% confidence interval (CI) of 1.0022–1.4888 (p = 0.0475). We also found a 1.14‐fold increased incidence of PC in Crohn's disease (CD) patients with (95% CI: 1.0017–1.3073, p = 0.0472). In the East Asian population, the incidence of hepatocellular carcinoma (HCC) was 1.28‐fold higher (95% CI = 1.0709–1.5244, p = 0.0065) in IBD patients than in the general population. Additionally, ulcerative colitis (UC) patients displayed 1.12‐fold (95% CI: 1.1466–1.3334, p < 0.0001) and 1.31‐fold (95% CI: 1.0983–1.5641, p = 0.0027) increased incidences of HCC and cholangiocarcinoma (CCA), respectively. Finally, the incidence of PC was 1.19‐fold higher in CD patients than in the general population (95% CI = 1.0741–1.3132, p = 0.0008). Conclusion: Our study validated that IBD is a risk factor for HPBC. This causal relationship exhibited significant heterogeneity in different European and East Asian populations. [ABSTRACT FROM AUTHOR]

Background: Kidney function can be impaired in patients with inflammatory bowel diseases (IBD), including Crohn's diseases (CD) and ulcerative colitis (UC). However, the causal relationship between IBD and chronic kidney diseases (CKD) remains unclear., Methods: We determined the causal association between IBD and CKD by performing two-sample bidirectional mendelian randomization (MR) analyses. Independent genetic variants were selected as instrumental variables (IVs) of the exposure from open-access genome-wide association studies (GWAS) among European ancestry. IVs-outcome estimates were extracted from three separate GWAS for IBD and two for CKD, respectively. Inverse-variance-weighted model was used as the primary MR method. The pleiotropic effect and heterogeneity were evaluated. For either direction, analyses were performed per outcome database and were subsequently meta-analysed., Results: Genetically predicted IBD was associated with higher risk of CKD (OR: 1.045, 95% CI: 1.016-1.073, P = 0.002) by including 42 344 IBD cases and 229 164 controls. Further analyses showed genetic liability to CD increased the risk of CKD (OR: 1.057, 95% CI: 1.027-1.087, p < 0.001) whereas UC did not (OR: 0.999, 95% CI:0.969-1.031, p = 0.970). In contrast, genetically predicted CKD was not associated with IBD (OR: 1.010, 95% CI: 0.965-1.056, p = 0.676), UC (OR: 1.011, 95% CI: 0.948-1.078, p = 0.746) and CD (OR: 1.024; 95% CI: 0.963-1.089, p = 0.447)., Conclusions: We concluded that CD, but not UC, can increase the risk of CKD causally. CD, but not UC, can increase the risk of chronic kidney disease causally. These findings enhance our understanding of the differential impact of IBD subtypes on CKD. It may be necessary to monitor kidney function regularly in patients with CD., (© 2024 Asian Pacific Society of Nephrology.)

Background: Ulcerative colitis (UC) is an inflammatory bowel disease with increasing prevalence worldwide. Current treatment strategies place considerable economic and humanistic burdens on patients. The aim of this study was to determine the socioeconomic burden of UC in adult patients in European countries in a real-world setting. Methods: In this retrospective, cross-sectional and observational pan-European study, patients with moderate or severe UC were assigned to ARM 1 and patients who had moderate or severe UC but achieved mild or remission status 12 months before index date (or clinical consultation date), were assigned to ARM 2. Clinical and medical resource use data were collected via electronic case report forms, and data on non-medical and indirect costs, and health-related quality of life (HRQoL) were collected via patient and public involvement and engagement (PPIE) questionnaires. Per-patient annual total costs per ARM and per country were calculated using the collated resource use in the last 12 months (between the start of the documentation period and patient consultation or index date) and country specific unit costs. Quality of life was described by arm and by country. Results: In the physician-reported eCRF population (n = 2966), the mean annual direct medical cost was €4065 in ARM 1 (n = 1835) and €2935 in ARM 2 (n = 1131). In the PPIE population (ARM 1, n = 1001; ARM 2, n = 647), mean annual direct cost was €4526 in ARM 1 and €3057 in ARM 2, mean annual direct non-medical cost was €1162 in ARM 1 and €1002 in ARM 2, mean annual indirect cost was €3098 in ARM 1 and €2309 ARM 2, and mean annual total cost was in €8787 in ARM 1 and €6368 in ARM 2. HRQoL scores showed moderate to high burden of UC in both groups. Conclusions: The cost and HRQoL burden were high in patients in both ARM 1 and ARM 2 indicating unmet needs in the UC active population. [ABSTRACT FROM AUTHOR]

Background: Crohn's disease and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by a progressive nature of the disease resulting in subsequent intestinal damage, limited efficacy of current treatments and suboptimal disease management and a significant burden for patients., Objectives: The IBD-PODCAST study aims to estimate the proportion of Crohn's disease and UC patients with suboptimal disease control (SDC) in a real-world setting., Methods: A non-interventional and cross-sectional study was conducted across 103 sites in 10 countries (Austria, Belgium, Canada, Germany, Greece, Italy, Portugal, Spain, Turkey, and UK). Criteria for SDC were based on STRIDE-II criteria and adapted by an expert panel., Results: 2185 patients (Crohn's disease: n = 1,108, UC: n = 1077) with a mean (SD) age of 44.0 (14.8) years and mean (SD) disease duration of 12.4 (9.2) years were included (52.2% male). Ileal involvement was present in 39.1% of Crohn's disease patients, 35.3% of UC patients had extensive colitis. 77.3% of Crohn's disease and 65.3% of UC patients were on targeted immunomodulators and, according to STRIDE-II-based treatment phases, 85.6% of Crohn's disease and 85.4% of UC patients were assigned to the long-term treatment phase. SDC was detected in 52.2% of Crohn's disease and 44.3% of UC patients predominantly due to impaired quality of life (QoL), clinically significant extraintestinal manifestations, steroid overuse, signs of active inflammation in UC and Crohn's disease, and active fistulas in Crohn's disease. More than one criterion was seen in 37% of patients with SDC. Opportunities for on-label treatment optimization were observed in 49% of Crohn's disease and 61% of UC patients on advanced therapy., Conclusion: The high percentage of SDC in this global, real-world cohort suggests a large disease burden and high unmet medical need in IBD patients. Future analysis should focus on monitoring and responding to SDC in this cohort and on patients' QoL., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: The Communicating Needs and Features of IBD Experiences (CONFIDE) study aimed to evaluate the experience and impact of ulcerative colitis (UC) symptoms on patients' lives and elucidate gaps in communication between patients and health care professionals (HCPs)., Methods: Online, quantitative, cross-sectional surveys of patients with moderate-to-severe UC and HCPs responsible for making prescribing decisions were conducted in the United States (US) and Europe. UC disease severity was defined by treatment, steroid use, and/or hospitalization history., Results: Surveys were completed by 200 US and 556 European patients and 200 US and 503 European HCPs. The most common UC symptoms experienced in the preceding month were diarrhea, bowel urgency, and increased stool frequency. Many patients (45.0% of US patients, 37.0% of European patients) reported wearing diapers/pads/protection at least once a week in the past 3 months due to fear/anticipation of fecal urge incontinence. The top reasons for declining participation in social events, work/school, and sports/exercise were due to bowel urgency and fear of fecal urge incontinence. HCPs ranked diarrhea, blood in stool, and increased stool frequency as the most common symptoms. While over half HCPs ranked bowel urgency as a top symptom affecting patients' lives, less than a quarter ranked it in the top 3 most impactful on treatment decisions., Conclusions: Similar disparities exist between patient and HCP perceptions in the United States and Europe on the experience and impact of UC symptoms. Bowel urgency has a substantial and similar impact on US and European patients, is underappreciated by HCPs, and should be addressed during routine appointments., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Budesonide MMX is a low bioavailability corticosteroid oral once-daily formulation, which has a controlled rate of release throughout the colon, thanks to the multimatrix (MMX) formulation. It has been available for a decade in the USA and Europe for the induction of remission in patients with active, mild to moderate ulcerative colitis, particularly for those not responsive to mesalamine. The efficacy of budesonide MMX in this setting has been assessed by registrative randomized controlled trials showing a higher rate of clinical and endoscopic remission at 8 weeks compared with placebo, mostly in patients with proctosigmoiditis and left-side colitis. Since it is available in our therapeutic armamentarium, a few studies have confirmed the effectiveness of budesonide MMX also in real-life, highlighting the high rate of clinical response and remission and the high safety profile. In the present review, we summarise clinical trials and real-life results of budesonide MMX, assessing its use and predictors of response and non-response in real-life. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have presented conflicting results on Western diets and the risk of inflammatory bowel disease (IBD). This study aimed to evaluate the role of a pre‐illness Western dietary pattern in the development of IBD. Methods: The Western dietary pattern was defined as that met at least two of the following, either a high intake of refined grains, red and processed meat, animal protein, animal fats or high‐fat dairy products, or with a low consumption of fruit and vegetables. Four medical databases (PubMed, EMBASE, the Cochrane Library and the China National Knowledge Infrastructure) were searched to identify all relevant references. Risk estimate and corresponding 95% confidence interval (CI) were pooled using a random‐effects model. Results: Nine studies (seven case‐control studies and two prospective cohorts) were included, with a total of 1491 IBD cases and 53 089 controls. A Western dietary pattern was associated with a risk of all IBD (relative risk [RR] 1.92, 95% CI 1.37‐2.68) and separately with Crohn's disease (CD) (RR 1.72, 95% CI 1.01‐2.93) and ulcerative colitis (UC) (RR 2.15, 95% CI 1.38‐3.34). Subgroup analysis by region showed that a Western dietary pattern was associated with the risk of CD and UC for studies performed in Europe (RR 2.25, 95% CI 1.44‐3.50 for CD; RR 2.65, 95% CI 1.61‐4.36 for UC). The pooled RR was 2.26 (95% CI 1.42‐3.59) in the pediatric CD subgroup. Conclusion: This meta‐analysis indicates that a pre‐illness Western dietary pattern may increase the risk of developing CD and UC. [ABSTRACT FROM AUTHOR]

Background and Aim: A definitive diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) is not always possible, and a proportion of patients will be diagnosed as inflammatory bowel disease unclassified (IBDU). The aim of the study was to investigate the prognosis of patients initially diagnosed with IBDU and the disease course during the following 5 years. Methods: The Epi‐IBD study is a prospective population‐based cohort of 1289 IBD patients diagnosed in centers across Europe. Clinical data were captured prospectively throughout the follow‐up period. Results: Overall, 476 (37%) patients were initially diagnosed with CD, 701 (54%) with UC, and 112 (9%) with IBDU. During follow‐up, 28 (25%) IBDU patients were changed diagnoses to either UC (n = 20, 71%) or CD (n = 8, 29%) after a median of 6 months (interquartile range: 4–12), while 84 (7% of the total cohort) remained IBDU. A total of 17 (15%) IBDU patients were hospitalized for their IBD during follow‐up, while 8 (7%) patients underwent surgery. Most surgeries (n = 6, 75%) were performed on patients whose diagnosis was later changed to UC; three of these colectomies led to a definitive diagnosis of UC. Most patients (n = 107, 96%) received 5‐aminosalicylic acid, while 11 (10%) patients received biologicals, of whom five remained classified as IBDU. Conclusions: In a population‐based inception cohort, 7% of IBD patients were not given a definitive diagnosis of IBD after 5 years of follow‐up. One in four patients with IBDU eventually was classified as CD or UC. Overall, the disease course and medication burden in IBDU patients were mild. [ABSTRACT FROM AUTHOR]

Cytokines, many of which signal through the JAK-STAT (Janus kinase-Signal Transducers and Activators of Transcription) pathway, play a central role in the pathogenesis of inflammatory and autoimmune diseases. Currently three JAK inhibitors have been approved for clinical use in USA and/or Europe: tofacitinib for rheumatoid arthritis, psoriatic arthritis and ulcerative colitis, baricitinib for rheumatoid arthritis, and ruxolitinib for myeloproliferative neoplasms. The clinical JAK inhibitors target multiple JAKs at high potency and current research has focused on more selective JAK inhibitors, almost a dozen of which currently are being evaluated in clinical trials. In this narrative review, we summarize the status of the pan-JAK and selective JAK inhibitors approved or in clinical trials, and discuss the rationale for selective targeting of JAKs in inflammatory and autoimmune diseases. [ABSTRACT FROM AUTHOR]

Introduction: Despite its success, there appears to be practical issues with Faecal Calprotectin (FC) testing in Inflammatory Bowel Diseases (IBD), including sample collection, delivery and processing delays. Patients' perception and barriers to FC testing are yet to be explored in clinical practice. Method: A prospective patient survey was undertaken at IBD units in UK, Europe and Australia. A 9- point patient-based questionnaire was completed in clinic and included demographics, previous FC testing and FC sample difficulty rating score. Predictors of testing difficulty were derived using multivariable logistic regression analysis. Results: A total of 585 patients with IBD completed the survey; 306 males with a median age of 43 years (IQR: 31-54). There were 446 patients (76%) who had prior FC testing experience. Of these, 37% (n=165) rated FC testing difficult; 'sample collection' (n=106; 67%) being the most common reason reported. Multivariable regression analysis identified age <49 years (odds ratio (OR): 2.5, CI:1.6-4.0), disease duration <35 months (OR 1.4, CI:0.9-2.1) and testing location (UK centre: OR 1.9, CI:1.2-3.1) as predictors of a difficult FC rating score. Conclusions: A total of 37% of patients find FC testing challenging, in particular those aged <49 years, disease duration <35 months. Further studies understanding and addressing these practical issues may aid higher FC uptake in clinic. [ABSTRACT FROM AUTHOR]

Objective: Vedolizumab is an antibody targeting α 4 β 7 integrin used in the treatment of ulcerative colitis (UC). Patients are commonly prescribed higher-than-standard doses if treatment response is inadequate, but little is known about the drivers and impact of increased dosing. Our objective was to use real-world data to describe vedolizumab dosages in current clinical practice, patient characteristics, physicians' reasons for prescribing vedolizumab, and physician treatment satisfaction., Methods: Data were derived from the Adelphi Real World UC vedolizumab Chart Review, a cross-sectional survey of gastroenterologists and their UC patients, conducted in France, Germany, Italy, Spain, and the United Kingdom between December 2022 and March 2023. Gastroenterologists provided data on patient demographics, clinical characteristics, treatment and vedolizumab dosage history, reasons for dose choice, and treatment satisfaction., Results: Data were returned on 448 patients by 112 gastroenterologists. Overall, 83.5% of patients were on a standard vedolizumab dose and 10.3% were on a higher-than-standard dose. The worsening of symptoms was the most cited reason for higher doses. Most reported symptoms at survey were fatigue, abdominal distention or pain, diarrhea, and bowel urgency, with the latter particularly in higher-than-standard dose patients. Patients on higher-than-standard dose had high rates of mild (37.0%) or moderate (26.1%) disease, and low rates of remission (33.8%). Physicians were dissatisfied with treatment control for 2.7% of standard and 26.1% of higher-than-standard dose patients., Conclusions: Over 10% of patients were receiving a higher-than-standard dose of vedolizumab, but despite this were found to have suboptimal clinical outcomes and low physician satisfaction.

Background: Inflammatory bowel disease is a global disease in the 21st century. We aimed to assess the changing incidence and prevalence of inflammatory bowel disease around the world.Methods: We searched MEDLINE and Embase up to and including Dec 31, 2016, to identify observational, population-based studies reporting the incidence or prevalence of Crohn's disease or ulcerative colitis from 1990 or later. A study was regarded as population-based if it involved all residents within a specific area and the patients were representative of that area. To be included in the systematic review, ulcerative colitis and Crohn's disease needed to be reported separately. Studies that did not report original data and studies that reported only the incidence or prevalence of paediatric-onset inflammatory bowel disease (diagnosis at age <16 years) were excluded. We created choropleth maps for the incidence (119 studies) and prevalence (69 studies) of Crohn's disease and ulcerative colitis. We used temporal trend analyses to report changes as an annual percentage change (APC) with 95% CI.Findings: We identified 147 studies that were eligible for final inclusion in the systematic review, including 119 studies of incidence and 69 studies of prevalence. The highest reported prevalence values were in Europe (ulcerative colitis 505 per 100 000 in Norway; Crohn's disease 322 per 100 000 in Germany) and North America (ulcerative colitis 286 per 100 000 in the USA; Crohn's disease 319 per 100 000 in Canada). The prevalence of inflammatory bowel disease exceeded 0·3% in North America, Oceania, and many countries in Europe. Overall, 16 (72·7%) of 22 studies on Crohn's disease and 15 (83·3%) of 18 studies on ulcerative colitis reported stable or decreasing incidence of inflammatory bowel disease in North America and Europe. Since 1990, incidence has been rising in newly industrialised countries in Africa, Asia, and South America, including Brazil (APC for Crohn's disease +11·1% [95% CI 4·8-17·8] and APC for ulcerative colitis +14·9% [10·4-19·6]) and Taiwan (APC for Crohn's disease +4·0% [1·0-7·1] and APC for ulcerative colitis +4·8% [1·8-8·0]).Interpretation: At the turn of the 21st century, inflammatory bowel disease has become a global disease with accelerating incidence in newly industrialised countries whose societies have become more westernised. Although incidence is stabilising in western countries, burden remains high as prevalence surpasses 0·3%. These data highlight the need for research into prevention of inflammatory bowel disease and innovations in health-care systems to manage this complex and costly disease.Funding: None. [ABSTRACT FROM AUTHOR]

Background/objectives: The role of long-term alcohol consumption for the risk of developing ulcerative colitis (UC) and Crohn's disease (CD) is unclear. For the first time, to prospectively assess the role of pre-disease alcohol consumption on the risk of developing UC or CD.Subjects/methods: Nested within the European Prospective Investigation into Cancer and Nutrition (EPIC-IBD), incident UC and CD cases and matched controls where included. At recruitment, participants completed validated food frequency and lifestyle questionnaires. Alcohol consumption was classified as either: non-use, former, light (⩽0.5 and 1 drink per week), below the recommended limits (BRL) (⩽1 and 2 drinks per day), moderate (⩽2.5 and 5 drinks per day), or heavy use (>2.5 and >5 drinks per day) for women and men, respectively; and was expressed as consumption at enrolment and during lifetime. Conditional logistic regression was applied adjusting for smoking and education, taking light users as the reference.Results: Out of 262 451 participants in six countries, 198 UC incident cases/792 controls and 84 CD cases/336 controls were included. At enrolment, 8%/27%/32%/23%/11% UC cases and 7%/29%/40%/19%/5% CD cases were: non-users, light, BRL, moderate and heavy users, respectively. The corresponding figures for lifetime non-use, former, light, BRL, moderate and heavy use were: 3%/5%/23%/44%/19%/6% and 5%/2%/25%/44%/23%/1% for UC and CD cases, respectively. There were no associations between any categories of alcohol consumption and risk of UC or CD in the unadjusted and adjusted odds ratios.Conclusion: There was no evidence of associations between alcohol use and the odds of developing either UC or CD. [ABSTRACT FROM AUTHOR]

Introduction: Thiopurine toxicity is related to genetic polymorphism. Thiopurine methyltransferase (TPMT) variants do not explain thiopurine toxicity in more than half of patients. Asians, despite the low prevalence of TPMT variants, are more susceptible to thiopurine toxicity. Since 2014, studies from many Asian countries have shown a strong association between nucleoside diphosphate-linked moiety X-type motif (NUDT) 15 polymorphism and thiopurine-induced myelotoxicity., Areas Covered: An English language literature search was performed for TPMT and NUDT15 genetic variants in inflammatory bowel disease and other diseases. This article discusses the merits of preemptive NUDT15 and TPMT testing in Asian and non-Asian IBD populations., Expert Opinion: The NUDT polymorphism occurs in up to 27% of the Asian and Hispanic population. Hematological toxicity occurs in up to one-third of patients with this genetic variant. Given this, preemptive testing for NUDT15 variant is worthwhile and is probably more cost-effective than TPMT testing in these groups. Prevalence of NUDT15 variants is low in non-Finnish European population, but NUDT15 variants have been linked to myelotoxicity along with TPMT genetic variants. NUDT15 preemptive testing should be considered in the migrant Asian population in Europe and North America and in Caucasian populations who develop myelotoxicity.

Introduction: Janus Kinase inhibitors (JAKi) are a new class of oral therapies for the treatment of moderate-severe ulcerative colitis with additional potential for the treatment of moderate-severe Crohn's disease. In contrast to biologic therapies JAKi provide the opportunity for non-immunogenic once or twice daily oral therapies., Areas Covered: Janus Kinase inhibitors for the treatment of ulcerative colitis and Crohn's disease based on mechanism of action, pharmacokinetics, clinical trial and real-world data regarding safety and efficacy; focusing on regulatory approvals in the U.S. and Europe., Expert Opinion: Janus Kinase inhibitors are considered among the 'advanced therapies' for IBD and are approved for the treatment of moderate to severe ulcerative colitis in adults with pending approvals for Crohn's disease in the U.S. JAKi offer non-immunogenic, oral options for patient not responding to other conventional agents but, have been 'restricted' by the FDA to patients with inadequate response to TNF blockers. JAKi offer rapidly acting oral alternatives to biologic agents for moderate-severe ulcerative colitis where the risks of cardiovascular and thrombotic events noted in rheumatoid arthritis have not been observed in IBD clinical trials. Nevertheless, monitoring of infections (primarily herpes zoster) and risk factors for cardiovascular and thrombotic complications is appropriate.

Background: Industrialization has been linked to the etiology of inflammatory bowel disease (IBD).Aim: We investigated the association between air pollution exposure and IBD.Methods: The European Prospective Investigation into Cancer and Nutrition cohort was used to identify cases with Crohn's disease (CD) (n = 38) and ulcerative colitis (UC) (n = 104) and controls (n = 568) from Denmark, France, the Netherlands, and the UK, matched for center, gender, age, and date of recruitment. Air pollution data were obtained from the European Study of Cohorts for Air Pollution Effects. Residential exposure was assessed with land-use regression models for particulate matter with diameters of <10 μm (PM10), <2.5 μm (PM2.5), and between 2.5 and 10 μm (PMcoarse), soot (PM2.5 absorbance), nitrogen oxides, and two traffic indicators. Conditional logistic regression analyses were performed to calculate odds ratios (ORs) with 95 % confidence intervals (CIs).Results: Although air pollution was not significantly associated with CD or UC separately, the associations were mostly similar. Individuals with IBD were less likely to have higher exposure levels of PM2.5 and PM10, with ORs of 0.24 (95 % CI 0.07-0.81) per 5 μg/m(3) and 0.25 (95 % CI 0.08-0.78) per 10 μg/m(3), respectively. There was an inverse but nonsignificant association for PMcoarse. A higher nearby traffic load was positively associated with IBD [OR 1.60 (95 % CI 1.04-2.46) per 4,000,000 motor vehicles × m per day]. Other air pollutants were positively but not significantly associated with IBD.Conclusion: Exposure to air pollution was not found to be consistently associated with IBD. [ABSTRACT FROM AUTHOR]

Background: To describe variations in treatment patterns, clinical outcomes, patient-reported outcomes (PRO), and physician and patient satisfaction in patients with moderate-to-severe ulcerative colitis (UC) treated with tofacitinib in a real-world setting., Methods: Data were drawn from the Adelphi UC Disease Specific Programme™, a point-in-time survey of physicians and their consulting patients in the US and Europe. For inclusion in this analysis, gastroenterologists completed medical record forms for the next seven consecutive consulting patients with confirmed UC, plus a further two patient record forms for patients treated with tofacitinib. Those same patients then completed a patient-reported questionnaire., Results: Gastroenterologists (n = 340) provided data for 2049 patients with UC, including 642 patients receiving tofacitinib. Physicians' most frequent reason for choosing tofacitinib was overall efficacy (71.3% of patients). The proportion of patients in remission increased with length of treatment, from 13.7% at [0, 4) weeks to 68.3% at [52+] weeks. Both physicians and patients reported that the Mayo components of stool frequency and blood in stool were reduced with time on treatment. Improvement in symptoms (bloody diarrhea, abdominal pain/cramps, urgency, rectal bleeding, fatigue/tiredness) was reported in the first weeks of treatment, and increased with time. At week [52+], mean score reductions from treatment initiation to current in overall symptom severity, pain, and fatigue were 2.2 (to a current mean score of 1.1), 2.2 (to 0.9), and 2.1 (to 1.0), respectively. Comparing patients at weeks [0, 4) and [52+] (all PROs, p < 0.0001), the increase in EQ-5D-5L index total score was 0.29 points and in SIBDQ total score was 20.5 points; percent reductions in WPAI absenteeism was 34.4%, presenteeism 26.8%, overall work impairment 40.9% and activity impairment was 28.3%. These changes reached the thresholds for minimally clinically important differences. The majority of physicians (91.9%) and patients (93.5%) were satisfied with tofacitinib at week [52+]., Conclusion: Patients with moderate-to-severe UC treated with tofacitinib show considerable improvement in symptoms and quality of life from tofacitinib initiation to one year and beyond, with high rates of remission. Physicians and patients report satisfaction with UC control at recommended doses in a mostly biologic experienced population., (© 2023. The Author(s).)

Introduction: Inflammatory autoimmune diseases (rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis, and psoriatic arthritis) have a considerable impact on patients' quality of life and healthcare budgets. Biosimilar infliximab (Remsima(®)) has been authorized by the European Medicines Agency for the management of inflammatory autoimmune diseases based on a data package demonstrating efficacy, safety, and quality comparable to the reference infliximab product (Remicade(®)). This analysis aims to estimate the 1-year budget impact of the introduction of Remsima in five European countries.Methods: A budget impact model for the introduction of Remsima in Germany, the UK, Italy, the Netherlands, and Belgium was developed over a 1-year time horizon. Infliximab-naïve and switch patient groups were considered. Only direct drug costs were included. The model used the drug-acquisition cost of Remicade. The list price of Remsima was not known at the time of the analysis, and was assumed to be 10-30% less than that of Remicade. Key variables were tested in the sensitivity analysis.Results: The annual cost savings resulting from the introduction of Remsima were projected to range from €2.89 million (Belgium, 10% discount) to €33.80 million (Germany, 30% discount). If any such savings made were used to treat additional patients with Remsima, 250 (Belgium, 10% discount) to 2602 (Germany, 30% discount) additional patients could be treated. The cumulative cost savings across the five included countries and the six licensed disease areas were projected to range from €25.79 million (10% discount) to €77.37 million (30% discount). Sensitivity analyses showed the number of patients treated with infliximab to be directly correlated with projected cost savings, with disease prevalence and patient weight having a smaller impact, and incidence the least impact.Conclusion: The introduction of Remsima could lead to considerable drug cost-related savings across the six licensed disease areas in the five European countries.Funding: Mundipharma International Ltd. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease affects more than 2 million people in Europe, with almost 20% of patients being diagnosed in pediatric age. Patients with inflammatory bowel disease are at increased risk of thromboembolic complications which may affect patients' morbidity and mortality. The risk of the most common thromboembolic events, such as deep venous thrombosis and pulmonary embolism, are estimated to be three-fold increased compared to controls, but many other districts can be affected. Moreover, patients with ulcerative colitis and Crohn's disease experience thromboembolic events at a younger age compared to general population. Many factors have been investigated as determinants of the pro-thrombotic tendency such as acquired risk factors or genetic and immune abnormalities, but a unique cause has not been found. Many efforts have been focused on the study of abnormalities in the coagulation cascade, its natural inhibitors and the fibrinolytic system components and both quantitative and qualitative alterations have been demonstrated. Recently the role of platelets and microvascular endothelium has been reviewed, as the possible link between the inflammatory and hemostatic process. [ABSTRACT FROM AUTHOR]

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

Biosimilars represent a novel category in the world of follow-up medicinal products with the requirement that they are highly similar but not identical to an approved originator biologic medicine, with no clinically meaningful differences in safety, purity, and potency. In this review, we discuss recent pivotal biosimilar developments for anti-inflammatory therapy in rheumatology, gastroenterology, and dermatology, and the influence of biosimilar availability on patients and payers. Finally, we provide our perspective on the evolution of biosimilar use in these indications in the United States (US) and in Europe and on where this evolution in biopharmaceuticals may lead in the future. Although biosimilars are commonly used in the European Union (EU), there will be an inevitable sea change of acceptance by clinicians, patients, payers, and regulators in the US. It is paramount to educate about biosimilarity, highlighting currently available data gathered from other geographies, in addition to gradually providing clinicians and patients with the necessary experience with these agents ultimately restoring competition in the biologics landscape., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective. The incidence of inflammatory bowel disease (IBD) in Europe has increased significantly. At least a fourth of patients are children. Mannan-binding lectin (MBL) is believed to be an important component of innate immunity, acting as an opsonin and activator of the lectin pathway (LP) of complement. The data relating any of the LP factors to IBD are sparse and contradictory and were obtained mainly from adult patients. The aim of this study was to investigate the possible role of MBL in Crohn's disease (CD) and ulcerative colitis (UC) in children. Methods. MBL2 gene single nucleotide polymorphisms (PCR-RFLP) and MBL concentrations (ELISA) were determined. Results. The frequency of MBL2 gene variants responsible for MBL deficiency (LXPA/O and O/O) is significantly higher in CD patients compared with controls or children with UC. A relatively high frequency of the codon 52 mutation (D allele) was noted in these patients. Practically no difference was found between UC and control (C) groups. Similarly, the average MBL levels as well as the number of MBL-deficient (MBL concentrations < 150 ng/ml) individuals differed between CD patients and controls or children suffering from UC. Again, there was no difference between UC and C groups. Conclusions. These data suggest that MBL deficiency may be associated with CD but not with UC in pediatric patients. The possible role of MBL in IBD requires confirmation in larger series and further investigation of the mechanisms involved. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: Inflammatory Bowel Disease (which includes Crohn''s Disease and Ulcerative Colitis), is a chronic condition characterised by substantial morbidity. Inflammatory Bowel Disease patients are considered expensive to manage, hence accurate estimates of care costs are crucial to help healthcare providers plan clinical management. The aim of this study is to estimate the cost of care for Crohn''s Disease and Ulcerative Colitis patients in the United Kingdom and Western mainland Europe. Methods: Decision models were built to simulate the natural disease history of Crohn''s Disease and Ulcerative Colitis, informed by United Kingdom and European clinical pathways. A healthcare provider perspective was adopted, model inputs were informed by published sources and expert opinion, and UK healthcare costs were used (2008 prices). Cohorts of 25year old patients presenting with symptoms of varying severity were modelled over ten years, and annual treatment costs calculated per patient. Results: The average annual cost of care per Crohn''s Disease/Ulcerative Colitis patient was £631/£762 (United Kingdom) and £838/£796 (Europe). Most costs were incurred immediately following diagnosis, particularly in European Crohn''s patients, reflecting the earlier use of more aggressive treatments. Surgery, hospitalisation, and the use of biological therapies and mesalazine (in Ulcerative Colitis) were key cost drivers. The total annual cost to the United Kingdom National Health Service of caring for Inflammatory Bowel Disease patients was estimated to be £131million. Conclusions: This study confirms that Inflammatory Bowel Disease patients are expensive to manage and illustrates the importance of differentiating between alternative clinical management scenarios. [Copyright &y& Elsevier]

OBJECTIVE: The aim of this study was to assess the efficacy and safety of adalimumab (ADA), a recombinant human monoclonal antibody against tumour necrosis factor α (TNF), for the induction of clinical remission in anti-TNF naïve patients with moderately to severely active ulcerative colitis. METHODS: This 8-week, multicentre, randomised, double-blind, placebo-controlled study (NCT00385736), conducted at 94 centres in North America and Europe, enrolled ambulatory adult patients with Mayo score of ≥6 points and endoscopic subscore of ≥2 points despite treatment with corticosteroids and/or immunosuppressants. Under the original study protocol, 186 patients were randomised (1:1) to subcutaneous treatment with ADA160/80 (160 mg at week 0, 80 mg at week 2, 40 mg at weeks 4 and 6) or placebo. Subsequently, at the request of European regulatory authorities, the protocol was amended to include a second induction group (ADA80/40: 80 mg at week 0, 40 mg at weeks 2, 4 and 6). The primary efficacy endpoint was clinical remission (Mayo score ≤2 with no individual subscore >1) at week 8, assessed in 390 patients randomised (1:1:1) to ADA160/80, ADA80/40, or placebo. Safety was assessed in all enrolled patients. Patients, study site personnel, investigators, and the sponsor were blinded to treatment assignment. RESULTS: At week 8, 18.5% of patients in the ADA160/80 group (p=0.031 vs placebo) and 10.0% in the ADA80/40 group (p=0.833 vs placebo) were in remission, compared with 9.2% in the placebo group. Serious adverse events occurred in 7.6%, 3.8% and 4.0% of patients in the placebo, ADA80/40, and ADA160/80 groups, respectively. There were two malignancies in the placebo group, none in the ADA groups. There were no cases of tuberculosis and no deaths. CONCLUSIONS: ADA160/80 was safe and effective for induction of clinical remission in patients with moderately to severely active ulcerative colitis failing treatment with corticosteroids and/or immunosuppressants. CLINICAL TRIAL: NCT00385736. [ABSTRACT FROM AUTHOR]

Background: Musculoskeletal disorders are well-defined extra-intestinal manifestations of inflammatory bowel diseases (IBD). There is little data regarding the frequencies of IBD and extra-intestinal manifestations from Central and East Europe and Middle Eastern countries.Aims: To determine the prevalence of peripheral arthritis in IBD and to document the relationship to other extra-intestinal manifestations.Methods: Enrolled in the study were 357 patients who were diagnosed with IBD from December 2002 through January 2008. All of the patients underwent a detailed whole-body examination by a gastroenterologist and rheumatologist.Results: IBD-related peripheral arthritis (IBDPA) was found in 66 (18.5%) of the 357 patients (28.3% Crohn's disease, 13.5% ulcerative colitis; p=0.001 χ=11.62). IBDPA was more frequent in female patients (60.6 vs. 39.4%, p=0.000, χ=11.12). In eight (12.1%) cases, IBDPA occurred before the onset of IBD. Acute self-limiting episodes, recurrences of the attacks, and persistent symptoms of arthritis were present in 40 (60.6%), 26 (39.3%), and 29 (45.7%) patients, respectively. Arthritis was symmetrical in 33 (50%) cases. Knees (65.2%) and ankles (62.1%) were the most commonly affected joints. Erythema nodosum and pyoderma gangrenosum were more common among patients with IBDPA than patients without it (p=0.001, χ=10.49, and p=0.000 χ=25.77, respectively).Conclusions: IBDPA is a frequent extra-intestinal complication of IBD. Those of female gender and the presence of Crohn's disease, erythema nodosum and pyoderma gangrenosum have a higher risk to develop IBDPA. [ABSTRACT FROM AUTHOR]

In a survey comprising 1,176 patients with inflammatory bowel disease (IBD) we recently showed that azathioprine (AZA) beyond 4 years is beneficial in ulcerative colitis (UC) patients and in a subset of Crohn's disease (CD) patients. Here, we show for the first time that azathioprine responsiveness depends on body mass index (BMI). The relationship is reciprocal in UC and CD, with a better outcome in UC patients with a BMI<25 and in CD patients with a BMI>25. These observations are particularly interesting considering the evolving concept of a relationship between fatty metabolism and immune regulation. Additionally, we show that CD patients, but not UC patients, respond better to AZA when it is started in clinical remission. This observation may support data favouring a "hit hard and early" regime in CD. Finally, we were able to demonstrate a decrease in the incidence of CD-related complications requiring surgery through treatment with AZA. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: The National UK IBD audit tool is an electronic database created to improve the quality and safety of care for IBD patients by auditing individual patient care, service resources and organisation against national standards. We used the National UK IBD audit tool to compare the organisation and process of IBD care between services in Oxford (UK) and Milan (Italy), as a pilot study to evaluate its application outside national boundaries. Methods: Clinical and demographic data of patients with CD and UC, consecutively admitted during a 2month period, were collected and compared between the centres, to each other and to the UK IBD standards obtained by previous audit analyses performed in Oxford in 2006. Results: 20 and 26 patients with UC were admitted in Oxford and Milan, as well as 21 and 20 patients with CD, respectively. Most admissions in Milan were planned admissions for moderately active treatment-refractory disease. No patient died. Oxford had a higher surgery rate. Endoscopy for UC consisted mainly of colonoscopy in Milan (92%) and flexible sigmoidoscopy in Oxford (64%). In CD, Oxford data revealed a higher use of immununomodulators and CT scan, compared with higher use of bowel ultrasound in Milan. CRP was the preferred biomarker of disease activity. The following areas did not reach the standards set for the 2006 UK IBD Audit: the lack in Milan of IBD specialist nurses and few dietitian visits, as well as little attention to heparin prophylaxis and abdominal radiography in UC. Both sites paid little attention to stool cultures and revealed a high rate of active smokers in CD and little attention to bone protection in steroids users. Since the 2006 audit in Oxford, improvements include IBD specialist nurse visits, dietitian visits, number of active smokers, stool samples, prophylactic heparin, bone protection and nutritional assessment. Conclusions: Consistent procedural differences between Oxford and Milan identified by audits of both UC and CD could be resolved by organisational change, with an improvement in the service. The UK IBD audit tool is an easy instrument to assess the processes and outcomes of care delivery in IBD and can be applied also outside UK. [Copyright &y& Elsevier]

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 × 10−9), 22q12 (rs2412973, P = 1.55 × 10−9), 10q22 (rs1250550, P = 5.63 × 10−9), 2q37 (rs4676410, P = 3.64 × 10−8) and 19q13.11 (rs10500264, P = 4.26 × 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. [ABSTRACT FROM AUTHOR]

Background & Aims: Management of Clostridium difficile infection in patients with flaring inflammatory bowel disease (IBD) has not been optimized. We investigated the effects of combination therapy with antibiotics and immunomodulators in patients with IBD and C difficile infection. Methods: We analyzed data from 155 patients (59% with ulcerative colitis [UC]) from a retrospective, European Crohn''s and Colitis organization, multi-center study comparing outcome of hospitalized IBD patients with C difficile infection who were treated with antibiotics (n = 51) or antibiotics and immunomodulators (n = 104). The primary composite outcome was death or colectomy within 3 months of admission, in-hospital megacolon, bowel perforation, hemodynamic shock, or respiratory failure. Results: The primary outcome occurred in 12% of patients given the combination treatment vs none of the patients given antibiotics alone (P = .01). UC, abdominal tenderness, or severe bloody diarrhea was more common among patients that received the combined therapy. However, multivariate analysis revealed that only the combination therapy maintained a trend for an independent association with the primary outcome (likelihood ratio = 11.9; CI, 0.9–157; P = .06). Treatment with 2 or 3 immunomodulators was correlated with the primary outcome, independent of disease severity at presentation (odds ratio [OR] = 17; CI, 3.2–91; P < .01). Acid-suppressing medications increased the risk of C difficile relapse (OR = 3.8; CI, 1.1–12.9; P = .03), whereas recent hospitalization correlated with increased rate of C difficile persistence (OR = 8; CI, 2.1–29; P = .002). Conclusions: Patients with IBD that also have C difficile infection are frequently treated with a combination of antibiotics and immunomodulators. However, this combination tends to associate with a worse outcome than antibiotic therapy alone. Prospective controlled trials are urgently needed to optimize the management of these challenging patients. [Copyright &y& Elsevier]

Background/Aims: The causes of ulcerative colitis are unknown, although it is plausible that dietary factors are involved. Case-control studies of diet and ulcerative colitis are subject to recall biases. The aim of this study was to examine the prospective relationship between the intake of nutrients and the development of ulcerative colitis in a cohort study. Methods: The study population was 260,686 men and women aged 20–80 years, participating in a large European prospective cohort study (EPIC). Participants were residents in the UK, Sweden, Denmark, Germany or Italy. Information on diet was supplied and the subjects were followed up for the development of ulcerative colitis. Each incident case was matched with four controls and dietary variables were divided into quartiles. Results: A total of 139 subjects with incident ulcerative colitis were identified. No dietary associations were detected, apart from a marginally significant positive association with an increasing percentage intake of energy from total polyunsaturated fatty acids (trend across quartiles OR = 1.19 (95% CI = 0.99–1.43) p = 0.07). Conclusions: No associations between ulcerative colitis and diet were detected, apart from a possible increased risk with a higher total polyunsaturated fatty acid intake. A biological mechanism exists in that polyunsaturated fatty acids are metabolised to pro-inflammatory mediators. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: A recent study reported that a nonsynonymous SNP rs2241880 (c.898A>G, p.Thr300Ala) within ATG16L1 confers susceptibility to Crohn''s disease (CD). We analyzed ATG16L1 c.898A>G in three independent European inflammatory bowel disease (IBD) cohorts from Germany, Hungary and the Netherlands. Methods: In total, we included 910 European IBD patients and compared the ATG16L1 c.898A>G genotype frequency with 707 ethnically matched healthy controls. We included patients from 3 populations originating from Germany (CD n =310; ulcerative colitis [UC] n =179), Hungary (CD n =147; UC n =117), and the Netherlands (CD n =157). Subtyping analysis was performed in respect to CARD15 alterations and clinical characteristics. Results: We found a highly significant association of c.898A>G to CD. The association was significant (p =0.0005) for the total CD cohort but also for the individual populations from Germany (p =0.02) and Netherlands (p =0.02) whereas in the Hungarian CD patients a clear trend was observed (p =0.19; OR 1.227, 95% CI 0.910; 1.654). No association was found between c.898A>G and UC. No statistical interactions were observed between ATG16L1 c.898A>G and CARD15 variants. Furthermore no association to a CD subphenotype was detected. Conclusions: We confirm that ATG16L1 variant c898A>G confers a risk variant for CD but is not associated with a distinct CD phenotype. [Copyright &y& Elsevier]

Abstract: Background: Scarce data are available in Europe on the cost of treatment for ulcerative colitis (UC). Aim: To assess the cost of illness of moderate-to-severe UC in two scenarios: traditional treatment versus alternative treatment incorporating granulocyte, monocyte adsorption – apheresis (GMA-Apheresis; Adacolumn®). To determine the relative cost-effectiveness of both options in steroid-dependent patients. Methods: One-year cost-of-illness and cost-effectiveness analysis from the third-payer perspective using a decision tree model was carried out. Probabilities of each event were derived from the literature and an expert panel. Direct medical costs were obtained from official sources (€2004). Effectiveness was measured by the proportion of patients achieving clinical remission. Results: The average annual cost per patient treated with traditional treatment was estimated to be €6740; with GMA-Apheresis, the cost was estimated to be €6959. In steroid-dependent patients, the average annual cost was €6059 and €11,436, respectively. The proportion of patients achieving clinical remission with GMA-Apheresis was 22.5% higher. As second- and third-line therapy, a new course of corticosteroids and surgery was avoided in 18.5 and 4% of patients, respectively. Conclusions: Incorporating GMA-Apheresis (Adacolumn®) in the therapeutic management of moderate-to-severe UC patients is cost-effective and implies savings related to the reduction of adverse effects derived from corticosteroid use and to the decreased number of surgical interventions. [Copyright &y& Elsevier]

Background: Population based studies have revealed varying mortality for patients with ulcerative colitis but most have described patients from limited geographical areas who were diagnosed before 1990. Aims: To assess overall mortality in a European cohort of patients with ulcerative colitis, 10 years after diagnosis, and to investigate national ulcerative colitis related mortality across Europe. Methods: Mortality 10 years after diagnosis was recorded in a prospective European-wide population based cohort of patients with ulcerative colitis diagnosed in 1991-1993 from nine centres in seven European countries. Expected mortality was calculated from the sex, age and country specific mortality in the WHO Mortality Database for 1995-1998. Standardised mortality ratios (SMR) and 95% confidence intervals (CI) were calculated. Results: At follow-up, 661 of 775 patients were alive with a median follow-up duration of 123 months (107-144). A total of 73 deaths (median follow-up time 61 months (1-133)) occurred compared with an expected 67. The overall mortality risk was no higher: SMR 1.09 (95% CI 0.86 to 1.37). Mortality by sex was SMR 0.92 (95% CI 0.65 to 1.26) for males and SMR 1.39 (95% CI 0.97 to 1.93) for females. There was a slightly higher risk in older age groups. For disease specific mortality, a higher SMR was found only for pulmonary disease. Mortality by European region was SMR 1.19 (95% CI 0.91 to 1.53) for the north and SMR 0.82 (95% CI 0.45-1.37) for the south. Conclusions: Higher mortality was not found in patients with ulcerative colitis 10 years after disease onset. However, a significant rise in SMR for pulmonary disease, and a trend towards an age related rise in SMR, was observed. [ABSTRACT FROM AUTHOR]

Background & Aims: The colectomy rate in ulcerative colitis (UC) is related to morbidity and to treatment decisions made during disease course. The aims of this study were to determine the colectomy risk in UC in the first decade after diagnosis and to identify factors that may influence the choice of surgical treatment. Methods: In 1991-1993, 781 UC patients from 9 centers located in 7 countries in northern and southern Europe and in Israel were included in a prospective inception cohort study. After 10 years of follow-up, 617 patients had complete medical records, 73 had died, and 91 had been lost to follow-up. Results: There were no significant differences in age, sex, or disease extent at diagnosis between patients followed for 10 years and those lost to follow-up. The 10-year cumulative risk of colectomy was 8.7%: 10.4% in the northern and 3.9% in the southern European centers (P < .001). Colectomy was more likely in extensive colitis than in proctitis, with an adjusted hazard ratio (HR) of 4.1 (95% CI: 2.0–8.4). Compared with the southern centers, the adjusted HR was 2.7 (95% CI: 1.3–5.6) for The Netherlands and Norway together and 8.2 (95% CI: 3.6–18.6) for Denmark. Age at diagnosis, sex, and smoking status at diagnosis had no statistically significant influence on colectomy rates. Conclusions: The colectomy rate was found to be lower than that in previous publications, but there was a difference between northern and southern Europe. Colectomy was associated with extensive colitis, but the geographic variations could not be explained. [Copyright &y& Elsevier]

OBJECTIVES: Studies in the US and Europe have shown that appendectomy may prevent the development of ulcerative colitis, but no detailed study has been conducted in Japan, where ulcerative colitis is uncommon and the population is racially homogeneous. In addition, there has been no detailed analysis of the relationship between appendectomy and the clinical course of ulcerative colitis. In this multi-center clinical study, we evaluated the effects of appendectomy on ulcerative colitis in Japan. METHODS: A case-control study was undertaken in seven medical institutions comparing the incidence of appendectomy and tonsillectomy in 325 patients with ulcerative colitis and 325 controls matched for age (10-yr intervals) and sex. Disease duration, extent, and prognosis were determined in 21 patients with ulcerative colitis who underwent appendectomies and 304 patients with ulcerative colitis who did not undergo appendectomies. RESULTS: Appendectomy was performed in a significantly lower percentage of patients in the ulcerative colitis group (21/325, 6.5%) than in the control group (53/325, 16.3%) (p < 0.001) (odds ratios = 0.355, 95% CI = 0.208-0.603). In contrast, no significant difference was observed between the groups with respect to tonsillectomy. The mean age (25.7 ± 10.9 yr) of patients with ulcerative colitis at the time of appendectomy was significantly higher than the mean age (20.1 ± 8.7 yr) of patients in the control group at the time of appendectomy (p < 0.05). The incidence of proctitis was higher in the appendectomy group than in the group that did not undergo appendectomies (38.1% vs 18.1%). In addition, the recurrence rates were significantly lower in the appendectomy group than in the group that did not undergo appendectomies (57.1% vs 78.6%, p < 0.05), although both groups were similar in composition as to sex, age, duration disease, smoking status, and previous medical treatment. CONCLUSIONS: Our results indicate that appendectomy has negative association with and perhaps a preventive effect the development of ulcerative colitis in the Japanese population. Furthermore, appendectomy also appears to reduce the extent and recurrence of ulcerative colitis. [ABSTRACT FROM AUTHOR]

Background: Over 2 million people in Europe are affected by ulcerative colitis, which often severely impacts the quality of life of those concerned. Among other factors, lifestyle and psychosocial factors seem to play an important role in pathogenesis and course of the disease and can be addressed as a complement to pharmacotherapy in comprehensive lifestyle modification programs., Methods: This qualitative study as part of a mixed methods approach was carried out in the framework of a randomized controlled trial that examined the effect of a comprehensive lifestyle-modification-program (10-week-day clinic program) on quality of life in patients with ulcerative colitis. Qualitative interviews were conducted with 20 out of 47 patients of the intervention group after the program. The aim was to deepen, supplement, and expand the quantitative results of the trial, i.e. to examine individual perceptions of the intervention, including subjective changes and the extent to which elements of the program were integrated into everyday life. Qualitative content analysis techniques utilizing the software MAXQDA were used., Results: Patients with ulcerative colitis in our sample often experienced multiple negative effects on different levels (physical, psychological, and social) and impaired quality of life because of their disease. They reported generally positively about the program itself, and emphasized perceived positive changes regarding their psychological and physical well-being. The interviews indicated a good implementation of elements learned during the intervention in everyday life., Conclusions: Through participation in a comprehensive lifestyle modification program in the structure of a day clinic complementary to pharmacotherapy, patients with ulcerative colitis can reduce psychosocial stress and physical symptoms and thereby actively improve their well-being and general quality of life. This patient-centered, holistic approach was rated as useful in countering the complex disease manifestation as well as meeting the individual needs of the patients regarding their disease., Trial Registration: clinicaltrials.gov NCT02721823., (© 2022. The Author(s).)

Background: Inflammatory bowel diseases (IBD), including Crohn disease (CD) and ulcerative colitis (UC), are complex disorders with multiple comorbidities. We conducted international patient and physician surveys to evaluate current experiences and perceptions of patients with CD or UC and physicians who treat IBD., Methods: The IBD Global Assessment of Patient and Physician Unmet Need Surveys comprised a patient survey and a physician survey, fielded in North America and Europe between August 16, 2019, and November 10, 2019. Adults with CD or UC (targeted 1:1 ratio) were recruited from physicians, patient advocacy groups, and recruitment panels; physicians were recruited by recruitment agencies and panels., Results: In total, 2398 patients with IBD (1368 CD, 1030 UC) and 654 physicians completed surveys. Anxiety and depression were the most common comorbidities among patients with IBD. Patients and physicians were generally aligned on treatment goals and patient-physician communication. Patients with IBD reported high quality-of-life impact by rectal urgency and need to use the toilet, which were rated as lower-impact by physicians. Patients defined remission based on symptoms; physicians defined remission based primarily on clinical tests. Patients expected current treatments to control their disease for a longer duration than did physicians. Patients expressed more concern about corticosteroid use compared with physicians; many physicians reported prescribing corticosteroids for more than 4 months per year in some patients., Conclusions: Patients could benefit from education about disease remission and expectations for current therapies. High corticosteroid use is concerning to patients, and physicians should minimize the use of corticosteroids for extended periods of time., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background: Congenital chloride diarrhoea [CLD] is a rare autosomal recessive disease caused by mutations in the solute family carrier 26 member 3 [SLC26A3] gene. Patients suffer from life-long watery diarrhoea and chloride loss. Inflammatory bowel disease [IBD] has been reported in individual patients with CLD and in scl26a3-deficient mice., Methods: We performed an international multicentre analysis to build a CLD cohort and to identify cases with IBD. We assessed clinical and genetic characteristics of subjects and studied the cumulative incidence of CLD-associated IBD., Results: In a cohort of 72 patients with CLD caused by 17 different SLC26A3 mutations, we identified 12 patients [17%] diagnosed with IBD. Nine patients had Crohn's disease, two ulcerative colitis and one IBD-unclassified [IBD-U]. The prevalence of IBD in our cohort of CLD was higher than the highest prevalence of IBD in Europe [p < 0.0001]. The age of onset was variable [13.5 years, interquartile range: 8.5-23.5 years]. Patients with CLD and IBD had lower z-score for height than those without IBD. Four of 12 patients had required surgery [ileostomy formation n = 2, ileocaecal resection due to ileocaecal valve stenosis n = 1 and colectomy due to stage II transverse colon cancer n = 1]. At last follow-up, 5/12 were on biologics [adalimumab, infliximab or vedolizumab], 5/12 on immunosuppressants [azathioprine or mercaptopurine], one on 5-ASA and one off-treatment., Conclusions: A substantial proportion of patients with CLD develop IBD. This suggests the potential involvement of SL26A3-mediated anion transport in IBD pathogenesis. Patients with CLD-associated IBD may require surgery for treatment failure or colon cancer., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Several adsorptive type devices for ulcerative colitis are used for the induction of remission in patients with active severe disease worldwide. In 2020, the novel apheresis device Immunopure for ulcerative colitis was launched in Japan. Immunopure, like the polyethylene terephthalate column, uses polyarylate, a type of polyester resin, as the adsorbent. Similar to the cellulose acetate column, Immunopure is filled with adsorbent beads and expected to provide ease of use, with minimal risk of column clogging. Immunopure adsorbs leukocytes and platelets, especially activated platelets and platelet-leukocyte aggregates. In this article, the capability of Immunopure is evaluated from clinical perspective based on a clinical trial in Japan/Europe. As a result, Immunopure is comparable to other products in clinical effectiveness and indicated for the treatment of patients with refractory moderate ulcerative colitis, making it highly useful in clinical practice., (© 2021 The Authors. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

We performed a genome-wide association analysis of 1,897,764 SNPs in 1,043 German ulcerative colitis (UC) cases and 1,703 controls. We discovered new associations at chromosome 7q22 (rs7809799) and at chromosome 22q13 in IL17REL (rs5771069) and confirmed these associations in six replication panels (2,539 UC cases and 5,428 controls) from different regions of Europe (overall study sample Prs7809799 = 8.81 × 10−11 and Prs5771069 = 4.21 × 10−8, respectively). [ABSTRACT FROM AUTHOR]

(1) Background: Tofacitinib is approved in Europe for the treatment of adults with moderately to severely active ulcerative colitis since 2018. Real-world efficacy and safety data are currently scarce. (2) Methods: We performed a retrospective multicenter study at three German tertiary outpatient clinics for inflammatory bowel diseases and included all patients who started tofacitinib therapy between August 2018 and March 2020. The primary endpoint was a combined endpoint of steroid-free clinical remission, steroid-free clinical response, or clinical response at week 8. Secondary endpoints were biochemical response at week 8, as well as steroid-free clinical remission, steroid-free clinical response or clinical response at week 24, respectively, adverse events by week 24, and need for colectomy by the end of follow-up. (3) Results: Thirty-eight patients with moderate-to-severe ulcerative colitis were included. Eleven patients (28.9%) achieved steroid-free clinical remission at week 8. Fifty-three percent of the patients were primary non-responders at week 8. Three severe adverse events (pneumonia, hospitalization for aggravation of ulcerative colitis, emergency colectomy due to colon perforation), and 12 adverse events were documented by week 8 of therapy. By the end of follow-up, seven patients (18.4%) had undergone colectomy. [ABSTRACT FROM AUTHOR]

Background & Aims: Endoscopic and histologic remission are important goals in the treatment of ulcerative colitis (UC). We investigated the correlation of the recently developed Paddington International Virtual ChromoendoScopy ScOre (PICaSSO) and other established endoscopic scores against multiple histological indices and prospectively assessed outcomes., Methods: In this prospective multicenter international study, inflammatory activity was assessed with high-definition and virtual chromoendoscopy in the rectum and sigmoid using the Mayo Endoscopic Score (MES), UC Endoscopic Index of Severity (UCEIS), and PICaSSO. Targeted biopsies were taken for assessment using Robarts Histological Index (RHI), Nancy Histological index (NHI), ECAP (Extent, Chronicity, Activity, Plus score), Geboes, and Villanacci. Follow-up data were obtained at 6 and 12 months after colonoscopy., Results: A total of 307 patients were recruited. There was strong correlation between PICaSSO and histology scores, significantly superior to correlation coefficients of MES and UCEIS with histology scores. A PICaSSO score of ≤3 detected histologic remission by RHI (≤3 + absence of neutrophils) with area under the receiver operating characteristic curve (AUROC) 0.90 (95% confidence interval [CI] 0.86-0.94) and NHI (≤1) AUROC 0.82 (95% CI 0.77-0.87). The interobserver agreement for PICaSSO was 0.88 (95% CI 0.83-0.92). At 6- and 12-months follow-up, PICaSSO score ≤3 predicted better outcomes than PICaSSO >3 (hazard ratio [HR] 0.19 [0.11-0.33] and 0.22 [0.13-0.34], respectively),} as well as PICaSSO 4-8 (HR 0.25 [0.12-0.53] and 0.22 (0.12-0.39), respectively) and similar to histologic remission., Conclusion: In this first real-life multicenter study, the PICaSSO score correlated strongly with multiple histological indices. Furthermore, PICaSSO score predicted specified clinical outcomes at 6 and 12 months, similar to histology. Thus, PICaSSO can be a useful endoscopic tool in the therapeutic management of UC., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Half of the patients with ulcerative colitis require at least one course of systemic corticosteroids in their lifetime. Approximately 75% of these patients will also require immunosuppressive drugs ( i.e. , thiopurines or biological agents) in the mid-term to avoid colectomy. Immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer, particularly in elderly and co-morbid patients, underlining the unmet need for safer alternative therapies. Granulocyte/monocytapheresis (GMA), a CE-marked, non-pharmacological procedure for the treatment of ulcerative colitis (among other immune-mediated diseases), remains the only therapy targeting neutrophils, the hallmark of pathology in ulcerative colitis. GMA has proven its efficacy in different clinical scenarios and shows an excellent and unique safety profile. In spite of being a first line therapy in Japan, GMA use is still limited to a small number of centres and countries in Europe. In this article, we aim to give an overview from a European perspective of the mechanism of action, recent clinical data on efficacy and practical aspects for the use of GMA in ulcerative colitis., Competing Interests: Conflict-of-interest statement: Domènech E has served as a speaker or has received research or education funding or advisory fees from Samsung, MSD, AbbVie, Takeda, Kern Pharma, Pfizer, Janssen, Celgene, Adacyte Therapeutics, Roche, Otsuka Pharmaceuticals, Ferring, Shire Pharmaceuticals, Tillots, ThermoFisher, Grifols, Gebro, and Gilead. Akbar A has received speaker fees or advisory fees from Takeda, Dr Falk, Abbvie, Janssen, Otsuka Pharmaceuticals, Adacyte therapeutics and MSD. Dignass AU has received research support or acted as a principal investigator for Abbvie, Dr. Falk Pharma, Celgene/BMS, Gilead/Galapagos, Janssen, Otsuka and Takeda; he has acted as a consultant for AbbVie, Amgen, Boehringer Ingelheim, Celgene/BMS, Celltrion, Dr Falk Pharma, Ferring, Fresenius Kabi, Janssen, MSD, Otsuka, Pfizer, Roche, Takeda, Tillotts, Pharmacosmos and Vifor; and has participated in speaker bureaus for AbbVie, Falk Foundation, Ferring, Janssen, Med Update, MSD, Otsuka, Pfizer, Roche, Takeda, Tillotts, and Vifor., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Inflammatory bowel disease (IBD) is a risk factor for C. difficile infection (CDI), which, in turn, complicates the clinical course of IBD. Fecal microbiota transplantation (FMT) is safe and effective in patients with IBD and recurrent CDI (rCDI). In our study, patients with IBD and rCDI received FMT by colonoscopy and were followed-up for 8 weeks. The primary outcome was negative C. difficile toxin 8 weeks after FMT. Eighteen patients with IBD were enrolled. Eight patients received sequential FMT either for pseudomembranous colitis or failure of single fecal infusion. At 8-week follow-up the C. difficile toxin was negative in 17 patients, and most (83%) experienced also improvement of IBD disease activity. Overall, we did not observe any serious adverse event.FMT appears to be highly effective and safe in patients with IBD and rCDI and is likely not only to eradicate CDI but also to improve disease activity of IBD.