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Objectives: Canada has one of the highest age-adjusted incidence and prevalence rates of inflammatory bowel disease (IBD). Large patient volumes and limited resources have created challenges concerning the quality of IBD care, but little is known about patients' experiences. This paper aimed to better understand patient-perceived barriers to IBD care., Methods: An exploratory qualitative approach was used for this study. Fourteen focus groups (with 63 total participants) were co-facilitated by a researcher and patient research partner across eight Canadian provinces in 2018. Patients diagnosed with IBD (>18 years of age) and their caregivers were purposefully recruited through Crohn's and Colitis Canada, gastroenterology clinics and communities, and national social media campaigns. Focus group sessions were recorded, transcribed, and analyzed using thematic analysis., Results: Most participants self-identified as being white and women. The analysis generated four key themes regarding patient-perceived barriers and gaps in access to IBD care: (1) gatekeepers and their lack of IBD knowledge, (2) expenses and time, (3) lack of holistic care, and (4) care that is not patient-centered. An additional four themes were generated on the topic of patient-perceived areas of health system improvement for IBD care: (1) direct access to care, (2) good care providers, (3) electronic records and passports, and (4) multidisciplinary care or an 'IBD dream team'., Conclusions: This research contributes to the limited global knowledge on patients' experiences accessing IBD care. It is valuable for the development of care plans and policies to target gaps in care. Patients have identified system-level barriers and ideas for improvement, which should be taken into consideration when implementing system redesign and policy change., Competing Interests: Declaration of conflicting interestsThe authors declare that there are no conflicts of interest.

Objectives: Multiple studies suggest that the EQ-5D may overestimate health-related quality of life (HRQoL) in patients with coeliac disease (CD). We aimed to develop and psychometrically test potentially relevant bolt-on dimensions to improve the measurement performance of the EQ-5D-5L in CD patients., Methods: The development and selection of bolt-ons were informed by a literature review on HRQoL in CD, expert and patient input. A cross-sectional online survey was conducted amongst 312 adult CD patients. Respondents completed the EQ-5D-5L, two condition-specific bolt-ons newly-developed for the present study [dining (DI) and gastrointestinal problems (GI)] and three existing bolt-ons [cognition (CO), sleep (SL) and tiredness (TI)]. The following psychometric properties were tested: ceiling, informativity, convergent and known-group validity, and dimensionality (confirmatory factor analysis)., Results: Adding the TI, SL, GI, DI and CO individual bolt-ons reduced the ceiling of the EQ-5D-5L (39%) to 17%, 23%, 24%, 26% and 37%, respectively. GI excelled with strong convergent validity with the Gastrointestinal Symptom Rating Scale total score (r s =0.71) and improved the discriminatory power for all known-groups. GI was the only bolt-on loading on a different factor from the five core dimensions, whereas the other four bolt-ons loaded onto the same 'psychosocial health' factor as the EQ-5D-5L anxiety/depression dimension., Conclusion: The DI, GI, SL and TI bolt-ons, especially the GI, enhance the validity of EQ-5D-5L in patients with CD, suggesting their value in capturing important HRQoL aspects potentially missed by the five core dimensions. These bolt-ons can be used in sensitivity analyses supporting health technology assessments and subsequent resource allocation decisions., (© 2024. The Author(s).)

Introduction: Crohn's disease (CD) is a chronic, relapsing immune mediated disease, which is one of the two major types of inflammatory bowel disease (IBD). Fistulizing CD poses a significant clinical challenge for physicians. Effective management of CD requires a multidisciplinary approach, involving a gastroenterologist and a GI surgeon while tailoring treatment to each patient's unique risk factors, clinical representations, and preferences., Areas Covered: This comprehensive review explores the intricacies of fistulizing CD including its manifestations, types, impact on quality of life, management strategies, and novel therapies under investigation., Expert Opinion: Antibiotics are often used as first-line therapy to treat symptoms. Biologics that selectively target TNF-α, such infliximab (IFX), have shown high efficacy in randomized controlled trials. However, more than 50% of patients lose response to IFX, prompting them to explore alternative strategies. Current options include adalimumab and certolizumab pegol combination therapies, as well as small-molecule drugs targeting Janus kinases such as Upadacitinib. Furthermore, a promising treatment for complex fistulas is mesenchymal stem cells such as Darvadstrocel (Alofisel), an allogeneic stem cell-based therapy. However, surgical interventions are necessary for complex cases or intra-abdominal complications. Setons and LIFT procedures are the most common surgical options.

Background: The risk of metachronous advanced neoplasia after diagnosing serrated polyps in patients with IBD is poorly understood., Methods: A retrospective multicenter cohort study was conducted between 2010 and 2019 at three tertiary centers in Montreal, Canada. From pathology databases, we identified 1587 consecutive patients with serrated polyps (sessile serrated lesion, traditional serrated adenoma, or serrated epithelial change). We included patients aged 45-74 and excluded patients with polyposis, colorectal cancer, or no follow-up. The primary outcome was the risk of metachronous advanced neoplasia (advanced adenoma, advanced serrated lesion, or colorectal cancer) after index serrated polyp, comparing patients with and without IBD., Results: 477 patients with serrated polyps were eligible (mean age 61 years): 37 with IBD, totaling 45 serrated polyps and 440 without IBD, totaling 586 serrated polyps. The median follow-up was 3.4 years. There was no difference in metachronous advanced neoplasia (HR 0.77, 95% CI 0.32-1.84), metachronous advanced adenoma (HR 0.54, 95% CI 0.11-2.67), and metachronous advanced serrated lesion (HR 0.76, 95% CI 0.26-2.18) risk. When comparing serrated polyps in mucosa involved or uninvolved with IBD, both groups had similar intervals from IBD to serrated polyp diagnosis (p > 0.05), maximal therapies (p > 0.05), mucosal inflammation, inflammatory markers, and fecal calprotectin (p > 0.05)., Conclusion: The risk of metachronous advanced neoplasia after serrated polyp detection was similar in patients with and without IBD. Serrated polyps in IBD occurred independently of inflammation. This helps inform surveillance intervals for patients with IBD diagnosed with serrated polyps., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Long-term data on ustekinumab in real-life Crohn's disease patients are still missing, though randomized controlled trials demonstrated it as a favorable therapeutic option. We aimed to evaluate ustekinumab's clinical efficacy, drug sustainability, and safety in a prospective, nationwide, multicenter Crohn's disease patient cohort with a three-year follow-up. Crohn's disease patients on ustekinumab treatment were consecutively enrolled from 9 Hungarian Inflammatory Bowel Disease centers between January 2019 and May 2020. Patient and disease characteristics, treatment history, clinical disease activity (Harvey Bradshaw Index (HBI)), biomarkers, and endoscopic activity (Simple Endoscopic Score for Crohn's Disease (SES-CD)) were collected for three-years' time. A total of 148 patients were included with an overall 48.9% of complex behavior of the Crohn's disease and 97.2% of previous anti-TNF exposure. The pre-induction remission rates were 12.2% (HBI), and 5.1% (SES-CD). Clinical remission rates (HBI) were 52.2%, 55.6%, and 50.9%, whereas criteria of an endoscopic remission were fulfilled in 14.3%, 27.5%, and 35.3% of the subjects at the end of the first, second, and third year, respectively. Dose intensification was high with 84.0% of the patients on an 8-weekly and 29.9% on a 4-weekly regimen at the end of year 3. Drug sustainability was 76.9% during the follow-up period with no serious adverse events observed. Ustekinumab in the long-term is an effective, sustainable, and safe therapeutic option for Crohn's disease patients with severe disease phenotype and high previous anti-TNF biological failure, requiring frequent dose intensifications., (© 2024. The Author(s).)

Background : Proton pump inhibitor (PPI) therapy is well-established for its effectiveness in reducing re-bleeding in high-risk peptic ulcer patients following endoscopic hemostasis. Vonoprazan (VPZ) has demonstrated the capacity to achieve gastric pH levels exceeding 4, comparable to PPIs. This study aims to evaluate the comparative efficacy of intravenous PPI infusion versus VPZ in preventing re-bleeding after endoscopic hemostasis in patients with high-risk peptic ulcers. Methods : A randomized, double-blind, controlled, and double-dummy design was employed. Patients with peptic ulcer bleeding (Forrest class IA/IB or IIA/IIB) who underwent endoscopic hemostasis were randomly assigned to either the PPI group or the VPZ group. Re-bleeding rates at 3, 7, and 30 days, the number of blood transfusions required, length of hospitalization, and ulcer healing rate at 56 days were assessed. Results: A total of 44 eligible patients were enrolled, including 20 patients (PPI group, n = 11; VPZ group, n = 9) with high-risk peptic ulcers. The mean age was 66 years, with 70% being male. Re-bleeding within 72 h occurred in 9.1% of the PPI group versus 0% in the VPZ group ( p = 1.000). There was no significant difference in re-bleeding rates within 7 days and 30 days (18.2% vs. 11.1%, p = 1.000). Additionally, the ulcer healing rate did not significantly differ between the groups (87.5% vs. 77.8%). Conclusions : This pilot study demonstrates comparable efficacy between oral vonoprazan and continuous PPI infusion in preventing recurrent bleeding events among high-risk peptic ulcer patients following successful endoscopic hemostasis.

Introduction: Biological therapies have become the standard treatment for ulcerative colitis (UC). However, clinical remission rates post-induction therapy remain modest at 40-50%, with many initial responders losing response over time. Current treatment strategies frequently rely on a 'trial and error' approach, leading to prolonged periods of ineffective and costly therapies for patients, accompanied by associated treatment complications., Area Covered: This review discusses current evidence on risk stratification tools for predicting therapeutic efficacy and minimizing adverse events in UC management. Recent studies have identified predictive factors for biologic therapy response. In the context of personalized medicine, the goal is to identify patients at high risk of progression and complications, as well as those likely to respond to specific therapies. Essential risk stratification tools include clinical decision-making aids, biomarkers, genomics, multi-omics factors, endoscopic, imaging, and histological assessments., Expert Opinion: Employing risk stratification tools to predict therapeutic response and prevent treatment-related complications is essential for precision medicine in the biological management of UC. These tools are necessary to select the most suitable treatment for each individual patient, thereby enhancing efficacy and safety.

Background and Aims: Tofacitinib (TFB) appears to be effective in the treatment of ulcerative colitis (UC); however, available real-world studies are limited by cohort size. TFB could be an option in the treatment of acute severe ulcerative colitis (ASUC). We aimed to investigate efficacy and safety of TFB in moderate-to-severe colitis and ASUC., Methods: This retrospective, international cohort study enrolling UC patients with ≥6-week follow-up period was conducted from February 1 to July 31, 2022. Indications were categorized as ASUC and chronic activity (CA). Baseline demographic and clinical data were obtained. Steroid-free remission (SFR), colectomy, and safety data were analyzed., Results: A total of 391 UC patients (median age 38 [interquartile range, 28-47] years; follow-up period 26 [interquartile range, 14-52] weeks) were included. A total of 27.1% received TFB in ASUC. SFR rates were 23.7% (ASUC: 26.0%, CA: 22.8%) at week 12 and 41.1% (ASUC: 34.2%, CA: 43.5%) at week 52. The baseline partial Mayo score (odds ratio [OR], 0.850; P = .006) was negatively associated with week 12 SFR, while biologic-naïve patients (OR, 2.078; P = .04) more likely achieved week 52 SFR. The colectomy rate at week 52 was higher in ASUC group (17.6% vs 5.7%; P < .001) and decreased with age (OR, 0.94; P = .013). A total of 67 adverse events were reported, and 17.9% resulted in cessation of TFB. One case of thromboembolic event was reported., Conclusions: TFB is effective in both studied indications. TFB treatment resulted in high rates of SFR in the short and long terms. Higher baseline disease activity and previous biological therapies decreased efficacy. No new adverse event signals were found., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background: Inflammatory bowel diseases (IBDs) are chronic conditions that negatively affect the patient's quality of life. With the spread of the biopsychosocial model, the role of mental health in the activity and course of inflammatory bowel disease is becoming more and more recognized. Our study aimed to assess the prevalence of anxiety and depression in IBD patients in our tertiary referral center and determine the predictive factors of these mental conditions. Methods: A total of 117 patients were included consecutively between 1 December 2021 and 28 February 2022. We used a questionnaire to gather demographic information, disease course, and IBD-specific symptoms. We assessed anxiety symptoms using the GAD-7 and depressive complaints using the PHQ-9 questionnaire. We evaluated disease activity using CDAI and pMayo scores. Results: Of the 117 patients (male/female: 63/54), 88 suffered from Crohn's disease, and 29 were diagnosed with ulcerative colitis. Only 6 patients were taking medication for mood disorders, and 38 individuals sought mental support during their lifetime. A total of 15% of the population suffered from moderate-severe anxiety disorder, and 22% were affected by moderate-severe depression. The GAD-7 and PHQ9 values showed a significant correlation between the number of stools, bloody stools, abdominal pain, number of flare-ups, and CDAI scores. Conclusions: Our study confirmed that there is a high incidence of anxiety and depressive symptoms among IBD patients. Our results highlighted the symptoms that could be associated with mental disorders. It is important to assess the mental status of IBD patients to improve their quality of life.

Background: Different endoscopic scoring systems for assessing ulcerative colitis (UC) severity are available. However, most of them are not correlated with disease extent., Objectives: Our study aimed to compare the predictive value of the PanMay score versus the endoscopic Mayo (MES), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and Dublin score in predicting long-term outcomes of UC., Design: This retrospective study enrolled consecutive UC patients who underwent colonoscopy before at least a 3-year follow-up., Methods: The PanMayo, MES, UCEIS, and Dublin scores and the baseline clinical and demographic characteristics of the participants were assessed. Endpoints were disease flare that required novel biological therapy, colectomy, and hospitalization. Patients were stratified using baseline clinical activity., Results: Approximately 62.8% of the 250 enrolled patients were in clinical remission. In these patients, the PanMayo, MES, and Dublin scores were positively associated with the risk of clinical flare. The MES score increased with clinical flare. The PanMayo score (>12 points), but not the MES score, was associated with the need for novel biological initiation and biological escalation. Furthermore, the Dublin and UCEIS scores of patients in remission who need novel biological treatment had a similar trend. Colectomy risk was associated with PanMayo and Dublin scores., Conclusion: The combined endoscopic assessment of disease extent and severity can be more accurate in predicting outcomes among patients with UC. PanMayo score can be utilized in addition to the existing scoring systems, thereby leading to a more accurate examination., Summary: UC endoscopic scores do not assess extension. Our study aimed to analyze the predictive value of the PanMayo score. Based on 250 patients, results showed that the long-term disease outcomes of UC could be predicted with the PanMayo score more accurately., Competing Interests: PW has been a speaker for Takeda, Pfizer, Janssen, Ferring, A. Menerini, and MSD, and an advisory board member for Pfizer, Takeda, and Sanzdos (Norvatis). KF has received speaker’s honoraria from AbbVie, Janssen, Ferring, Takeda, and Goodwill Pharma. PLL has been a speaker and/or advisory board member: AbbVie, Amgen, BioJamp, Bristol Myers Squibb, Fresenius Kabi, Genetech, Gilead, Janssen, Merck, Mylan, Organon, Pendopharm, Pfizer, Roche, Sandoz, Takeda, Tillots, and Viatris and has received unrestricted research grant: AbbVie, Gilead, Takeda, and Pfizer. TM has received speaker’s honoraria from MSD, AbbVie, Egis, Goodwill Pharma, Takeda, Pfizer, Janssen, Sandoz, MundiPharma, Phytotec, Roche, Fresenius, and Teva. PB, TR, EF, BV, BF, MR, TB, WA, AB, AF, RB, and ZS have no conflict of interest to disclose., (© The Author(s), 2024.)

Introduction: Crohn's disease (CD) is a chronic inflammatory bowel disease characterized by unpredictable flare-ups and periods of remission. While several therapeutic options, such as anti-tumor necrosis factor (TNF), anti-integrin, and interleukin (IL) 12/23 inhibitors, as well as IL-23 and Janus kinase (JAK) inhibitors, have been approved for CD treatment, a substantial number of patients fail to respond adequately or experience a loss of response over time. In recent years, the scientific community has been actively investigating novel agents to address these challenges and improve the management of CD., Areas Covered: This comprehensive narrative review provides an overview of recent developments in CD treatment, summarizing phase 2 and phase 3 clinical trial data. We delve into the clinical efficacy and safety profiles of emerging therapies, encompassing JAK inhibitors, IL-23 inhibitors, anti-adhesion molecules, S1P1 receptor modulators, and combined targeted treatments., Expert Opinion: The armamentarium of CD therapeutic agents is constantly expanding. We analyze pivotal findings from phase 2 and phase 3 CD treatment trials. We also underscore the existing gaps in therapy and the paramount role of ongoing research and innovation in CD management.

Background: Few population-based studies have investigated the prevalence and disease course of perianal manifestation in Crohn's disease., Aims: To analyse the prevalence and outcomes of perianal Crohn's disease including medical therapies and need for perianal surgery, over different therapeutic eras based on the time of diagnosis; cohort A (1977-1995), cohort B (1996-2008), and cohort C (2009-2018) METHODS: Patient inclusion lasted between 1977 and 2018. We followed patients prospectively, and regularly reviewed both in-hospital and outpatient records. We defined a perianal surgical procedure as any perianal incision and excision, fistulotomy, or abscess drainage., Results: We included 946 incident patients. Perianal disease at diagnosis was present in 17.4% (n = 165) of the total cohort, with a declining prevalence in cohorts A/B/C, respectively (24.7%/18.5%/13.2%; p = 0.001). By the end of follow-up, an additional 9.3% (n = 88) of the total cohort developed perianal disease. Cumulative immunosuppressive and biologic exposure increased over time; biologic use was higher in patients with perianal disease [pLog Rank < 0.001]. The overall rate of perianal surgery was 44.7% (113/253), with a probability of 28.3% (95% CI: 25.4-31.2) after 10 years, 41.0% (95% CI: 37.5-44.5) after 20 years, and 64.1% (95% CI: 59-69.2) after 30 years. There was no statistically significant difference in the probability of first perianal surgery among cohorts A/B/C [Log Rank = 0.594]., Conclusions: The burden of perianal disease and perianal surgery rates were high in this cohort. Therapeutic strategy was accelerated in patients with perianal Crohn's over time with higher exposure to immunosuppressives and biologics. Surgical management of perianal disease remained unchanged amongst the cohorts., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: We aimed to evaluate clinical efficacy, biomarker activity, therapeutic drug monitoring (TDM), adverse events (AEs), and nocebo effect in inflammatory bowel disease (IBD) patients who underwent non-medical biosimilar switching., Methods: A prospective observational study of consecutive IBD patients who underwent biosimilar switch. Disease activity, biomarkers, TDM, and AEs, including the nocebo effect were captured 8 weeks before switch, at the time of switch (baseline),12 and 24 weeks after the switch., Results: 210 patients were included [81.4% had Crohn's disease (CD), the median age at inclusion: 42 years (IQR 29-61)]. There was no significant difference in the rates of clinical remission at week 8 before switch, baseline, week12, and 24 after switch: 89.0%,93.4%,86.3%,and 90.8%,p = 0.129. The biomarker remission rates were not significantly different; CRP:81.3%,74.7%,81.2%,73.0%,p = 0.343; fecal calprotectin: 78.3%,74.5%,71.7%,76.3%,p = 0.829. The rates of maintaining therapeutic levels (84.7%,83.9%,83.0%,85.3%,p = 0.597) and prevalence of positive anti-drug antibodies remained unchanged. Drug persistence at 12 week of switch was 97.1%, regardless of disease phenotype and originator. The nocebo effect was observed in 13.3%. The discontinuation rate was 4.8%., Conclusion: Despite a significant number of early nocebo complaints within the first 6 months after the biosimilar switch, no significant changes were found in clinical efficacy, biomarkers, therapeutic drug level, or anti-drug antibodies., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Few population-based studies have investigated long-term surgery rates for Crohn's disease [CD]. Our aim was to analyse disease progression and surgery rates in a population-based cohort over different therapeutic eras, based on the time of diagnosis: cohort-A [1977-1995], cohort-B [1996-2008], and cohort-C [2009-2018]., Methods: A total of 946 incident CD patients were analysed (male/female: 496/450; median age at diagnosis: 28 years [y]; interquartile range [IQR]: 22-40]). Patient inclusion lasted between 1977 and 2018. Immunomodulators have become widespread in Hungary since the mid-1990s and biologic therapies since 2008. Patients were followed prospectively, with both in-hospital and outpatient records reviewed regularly., Results: The probability of disease behaviour progression from inflammatory [B1] to stenosing or penetrating phenotype [B2/B3] significantly decreased (27.1 ± 5.3%/21.5 ± 2.5%/11.3 ± 2.2% in cohorts A/B/C, respectively, after 5 years; 44.3 ± 5.9%/30.6 ± 2.8%/16.1 ± 2.9% after 10 years, respectively; [pLogRank <0.001]). The probability of first resective surgery between cohorts A/B/C were 33.3 ± 3.8%/26.5 ± 2.1%/28.1 ± 2.4%, respectively, after 5 years; 46.1 ± 4.1%/32.6 ± 2.2%/33.0 ± 2.7% after 10 years, respectively; and 59.1 ± 4.0%/41.4 ± 2.6% [cohorts A/B] after 20 years. There was a significant decrease in first resective surgery risk between cohorts A and B [plog rank = 0.002]; however, no further decrease between cohorts B and C [plog rank = 0.665]. The cumulative probability of re-resection in cohorts A/B/C was decreasing over time (17.3 ± 4.1%/12.6 ± 2.6%/4.7 ± 2.0%, respectively, after 5 years [plog rank = 0.001])., Conclusion: We report a continuous decline in reoperation rates and disease behaviour progression in CD over time, with the lowest values in the biologic era. In contrast, there was no further decrease in the probability of first major resective surgery after the immunosuppressive era., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Inflammatory Bowel Disease (IBD) significantly affects women in their reproductive years. Understanding the relationship between IBD and pregnancy is crucial, given its impact across pre-gestational, gestational, and postpartum phases. Monitoring IBD activity during pregnancy involves various modalities. This review discusses these modalities, focusing on the efficacy and safety of Small Intestine Ultrasound (IUS) as a noninvasive and reliable option. While IUS has gained popularity, its technique-sensitive nature necessitates trained staff for optimal usage.

Biologicals and small molecules have revolutionized the medical management of inflammatory bowel diseases (IBD), yet they are only effective in a proportion of patients, and their impact on changing the natural history of the disease is still debatable. Recently, the concept of combining targeted biologics and small-molecule therapies has been introduced to the treatment of IBD. Dual-targeted therapy (sequential and combined), which is the combination of two targeted therapies, might be a reasonable choice for patients to break through the therapeutic ceiling. A recent randomized clinical trial (VEGA) provided the first controlled evidence that the short-term combination of two biological agents may lead to superior disease control than either of the agents alone in patients with ulcerative colitis (UC) without jeopardizing safety. Multiple studies are underway in both Crohn's disease and UC. Additionally, real-world evidence is accumulating in IBD patients receiving combination therapies with concomitant IBD and extraintestinal manifestations or in patients with medically refractory IBD. Of note, the majority of these patients were exposed to multiple biological agents earlier and lost response to at least one of the agents in the combination. This review summarizes current knowledge regarding this attractive novel therapeutic option in IBD. Clearly, more controlled data are needed to evaluate optimal timing, efficacy, and mitigation of safety concerns., Competing Interests: P.L.L. has been a speaker and/or advisory board member: AbbVie, Amgen, BioJamp, Bristol Myers Squibb, Fresenius Kabi, Genetech, Gilead, Janssen, Merck, Mylan, Organon, Pendopharm, Pfizer, Roche, Sandoz, Takeda, Tillots, and Viatris and has received unrestricted research grant: AbbVie, Gilead, Takeda, and Pfizer. P.W. has been a speaker for Takeda, Pfizer, Janssen, Ferring, A. Menerini, and MSD, and an advisory board member for Pfizer, Takeda, and Sanzdos (Norvatis)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

Background: Coeliac disease (CD) is a life-long food-related disorder with a global prevalence of approximately 1%. Patients with CD often experience reduced health-related quality of life that could improve with a strict adherence to a gluten-free diet (GFD)., Objectives: To obtain visual analogue scale (VAS), time trade-off (TTO) and willingness-to-pay (WTP) values amongst patients with CD., Methods: In 2020-2021, a cross-sectional online survey was conducted amongst 312 adult CD patients in Hungary. Patients completed the Gastrointestinal Symptom Rating Scale (GSRS) and evaluated their current health and three hypothetical health state vignettes defined based on dietary adherence using VAS, conventional 10-year TTO and WTP. Multivariate regressions were used to explore the effect of patients' demographic and clinical characteristics on utility and WTP values., Results: Mean VAS values for current health and 'CD with strict adherence to GFD', 'CD with loose adherence to GFD' and 'CD without GFD' hypothetical health states were 79.69 ± 18.52, 85.36 ± 16.18, 62.44 ± 19.91 and 36.69 ± 25.83, respectively. Corresponding mean TTO utilities were: 0.90 ± 0.19, 0.91 ± 0.20, 0.87 ± 0.23 and 0.76 ± 0.29. Mean annual WTP values for returning to full health were: €845 ± 1077, €648 ± 1002, €862 ± 1135 and €1251 ± 1496. Older age at diagnosis, male sex, more severe gastrointestinal symptoms (GSRS) and having comorbidities were associated with lower VAS and TTO or higher WTP values for current own health (p < 0.05)., Conclusion: This is the first study to report TTO utilities for CD health states. Strict adherence to the GFD may result in substantial health gains in symptomatic patients. Utilities and WTP results can be used to estimate benefits of GFD in cost-utility and cost-benefit analyses., (© 2023. The Author(s).)

Background: Endoscopic healing is a key treatment target in inflammatory bowel disease; few data are available on the clinical and endoscopic efficacy of biological therapy in upper gastrointestinal Crohn's disease. This study aimed to investigate small bowel mucosal healing and clinical efficacy of adalimumab therapy by video capsule endoscopy in patients with endoscopically active upper gastrointestinal Crohn's disease., Methods: This prospective, open-label, single-arm study included Crohn's disease patients with moderate-severe endoscopic proximal small bowel involvement, defined by a Lewis score >790. Patients were treated with adalimumab monotherapy for 24 weeks. Co-primary outcomes were endoscopic healing, defined as Lewis score <350, and endoscopic response, defined as >50% decrease in Lewis score. Secondary outcomes included clinical (Harvey-Bradshaw index <4) and biomarker remission (fecal calprotectin <250 μg/g, and C-reactive protein <5 mg/L)., Results: A total of 59 Crohn's disease patients were screened; 17 patients have met eligibility criteria and were enrolled. Endoscopic healing was observed in 8 patients (47.1%) and endoscopic response in additional 5 patients (29.4%) at 24 weeks. Median Lewis score was significantly decreased compared to baseline (1912 vs. 337, P = .0005). Eleven of 13 patients (84.6%) with clinical activity achieved clinical remission (baseline: 13/17 vs. week 24: 2/17, P < .0001). Nine of 10 patients with elevated C-reactive protein achieved normal C-reactive protein after treatment and the median C-reactive protein significantly decreased from 7.4 to 1.6 mg/L, P = .032. In contrast, no change was observed in fecal calprotectin pre- and posttreatment., Conclusions: Adalimumab induced endoscopic healing and clinical remission in patients with active small bowel Crohn's disease, with approximately half of the patients achieving endoscopic healing.

Background: Real-life data on the efficacy of ustekinumab as first-line therapy for the treatment of luminal Crohn's disease (CD) compared with anti-tumor necrosis factor (anti-TNF) agents are lacking. We compared the clinical response rates at 3 months in 2 cohorts of biologic-naïve patients treated by ustekinumab and anti-TNF agents., Methods: Biologic-naïve patients starting either ustekinumab or an anti-TNF agent for luminal CD between 2016 and 2019 in 2 tertiary centers were retrospectively included. The primary endpoint was clinical response at 3 months, defined as a Harvey-Bradshaw Index <4 or a 3-point drop in the score without steroids, need for CD-related surgery, or treatment discontinuation owing to failure or intolerance. Patients treated with ustekinumab were matched to patients receiving anti-TNF agents by a propensity score algorithm., Results: We included 156 patients starting anti-TNF agents (95 adalimumab and 61 infliximab) and 50 ustekinumab. After matching, clinical response rates at 3 months were 64% and 86% in the ustekinumab and anti-TNF groups, respectively (P = .01). At 12 months, in multivariate analysis adjusted for disease duration, location, concomitant immunosuppressant and steroids, and symptoms, clinical remission was independently associated with the biological therapy received (odds ratio, 2.6 for anti-TNF agent vs ustekinumab; P = .02). With a median follow-up duration of 40 (interquartile range, 23-52) months, no difference was observed in terms of time to drug withdrawal (P = .29) or safety., Conclusions: This retrospective real-world data suggest that an anti-TNF agent as a first-line biological therapy is associated with higher rates of response at 3 months than ustekinumab in patients with CD., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Few populaion-based studies have investigated the long-term colectomy rates of ulcerative colitis [UC]. We aimed to assess the colectomy rates over 40 years of different therapeutic eras in a prospective population-based inception cohort from Veszprem Province, Western Hungary., Methods: Patient inclusion lasted between January1, 1977, and December31, 2018. Patient follow-up ended December 31, 2020. Colectomy rates and disease course were examined in three different eras based on the time of UC diagnosis; cohort A [1977-1995], cohort B [1996-2008], and cohort C [2009-2018]., Results: A total of 1370 incident UC patients were included [male 51.2%, median age at diagnosis 37 years]. Median follow-up was 17 years (interquartile range [IQR] 9-24); 87 patients [6.4%] underwent colectomy. The cumulative probability of colectomy in the total population was 2.6% (95% confidence interval [CI] 2.2-3.0), 4.2% [95% CI 3.6-4.8], 7.0% [95% CI 6.2-7.8], and 10.4% [95% CI 9.1-11.7] after 5, 10, 20, and 30 years, respectively. The proportion of extensive colitis at diagnosis increased over time [24.2%/24.3%/34.9% in cohorts A/B/C, respectively, p = 0.001]. Overall exposure to immunomodulators [11.3%/20.9%/34.4% in cohorts A/B/C, respectively, p <0.001], as well as the probability for biologic therapy initiation increased over time (0%/3.3% [95% CI 2.6-4.0]/13.9% [95% CI 12.1-15.7], p <0.001). There were no statistically significant differences in the cumulative probability of colectomies between cohorts A/B/C: 1.7% [95% CI 1.0-2.4], 2.5% [95% CI 1.9-3.1], and 3.7% [95% CI 2.7-4.7] after 5 years; 3.5% [95% CI 2.5-4.5], 4.2% [95% CI 3.4-5.0], and 4.5% [95% CI 3.3-5.7] after 10 years; and 7.5% [95% CI 6.1-8.9] and 6.3% [95% CI 5.2-7.4] in cohorts A/B after 20 years [log-rank = 0.588]. Extensive colitis (hazard ratio [HR] 2.24, 95% CI 1.55-3.23) and continuous active disease activity [HR 6.36, 95% CI 3.46-11.67] were independent predictors for colectomy., Conclusion: No differences in colectomy rates have been observed in the incident UC patients over 40 years despite increasing use of immunomodulators and biologic therapies., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The cost of caring for patients with inflammatory bowel disease (IBD) continues to increase worldwide. The cause is not only a steady increase in the prevalence of Crohn's disease and ulcerative colitis in both developed and newly industrialised countries, but also the chronic nature of the diseases, the need for long-term, often expensive treatments, the use of more intensive disease monitoring strategies, and the effect of the diseases on economic productivity. This Commission draws together a wide range of expertise to discuss the current costs of IBD care, the drivers of increasing costs, and how to deliver affordable care for IBD in the future. The key conclusions are that (1) increases in health-care costs must be evaluated against improved disease management and reductions in indirect costs, and (2) that overarching systems for data interoperability, registries, and big data approaches must be established for continuous assessment of effectiveness, costs, and the cost-effectiveness of care. International collaborations should be sought out to evaluate novel models of care (eg, value-based health care, including integrated health care, and participatory health-care models), as well as to improve the education and training of clinicians, patients, and policy makers., Competing Interests: Declaration of interests JB reports personal fees from AbbVie, Celgene, Pfizer, Samsung Bioepis, Pharmacosmos, Ferring, and Galapagos; grants and personal fees from Janssen, MSD, Takeda, Tillots Pharma, and Bristol Myers Squibb; and grants from Novo Nordisk. MZ has received support for attending a meeting from Takeda. PDC has received grants or contracts from Janssen, Takeda, Ferring, Shire, AbbVie, Celltrion, and Baxter. PDC has been a speaker, consultant, and advisory board member for AbbVie, Janssen, Takeda, Celltrion, Ferring, Shire, and Baxter; received support for travel or attending meetings or both from Ferring, Shire, Janssen, AbbVie, Takeda, Celltrion, and Baxter; and has been a member of the Australia and New Zealand IBD Research Consortium. SV has received research grants from Pfizer, Galapagos, AbbVie, Johnson & Johnson, and Takeda; consulting fees from AbbVie, AbolerIS Pharma, Agomab, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, CVasThera, Cytoki Pharma, Dr Falk Pharma, Ferring, Galapagos, Genentech–Roche, Gilead, GSK, Hospira, Imidomics, Janssen, Johnson & Johnson, Eli Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillots Pharma, Zealand Pharma; speaker fees from Alimentiv, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Ferring, Galapagos, Genentech–Roche, Gilead, GSK, Janssen, Johnson & Johnson, Eli Lilly, Materia Prima, Pfizer, Takeda, and Tillots Pharma. CNB has served on advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb Canada, JAMP Pharma, Roche Canada, Janssen Canada, Sandoz Canada, Takeda Canada, and Pfizer Canada; is a consultant for Mylan Pharmaceuticals and Takeda; and educational grants from AbbVie Canada, Pfizer Canada, Takeda Canada, and Janssen Canada. CNB is on the speaker's panel for AbbVie Canada, Janssen Canada, Medtronic Canada, and Takeda Canada; and has received research funding from AbbVie Canada and Pfizer Canada. GGK has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer, Amgen, Sandoz, Pendopharm, and Takeda. He has received research support from Ferring. He shares ownership of a patent: treatment of inflammatory disorders, autoimmune disease, and pbc (WO2019046959A1. PCT/CA2018/051098) since Sept 7, 2018. DD has received lecture or consultancy fees from Takeda, Janssen, and Pfizer, and support for travel or attending meetings or both from Janssen and Takeda. MW has received grants or contracts from Mitsubishi Tanabe Pharma, Takeda, Zeria Pharmaceutical, Nippon Kayaku, Mochida Pharmaceutical, Kyorin Pharmaceutical, AbbVie, EA Pharma, Kissei Pharmaceutical, and Alfresa Pharma; consulting fees from AbbVie, EA Pharma, Eli Lilly Japan, Gilead Sciences, Nippon Boehringer Ingelheim, and Takeda Pharmaceutical; and honoraria from EA Pharma, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Zeria Pharmaceutical, Pfizer Japan, Kissei Pharmaceutical, Nippon Boehringer Ingelheim, Gilead Sciences, Janssen Pharmaceutical, Celltrion Healthcare, JIMRO, Eli Lilly Japan, and Mochida Pharmaceutical. LT has received grants or contracts from Janssen, AbbVie, Pfizer, Takeda, Roche, Gilead, Sandoz, and Amgen; consulting fees from Janssen, AbbVie, Pfizer, Takeda, Roche, Gilead, Sandoz, Amgen, Fresnius Kabi, and Viatris; and honoraria for lectures from Janssen, AbbVie, Pfizer, Takeda, Roche, Gilead, Sandoz, Amgen, and Organon. KP is an employee of Genentech–Roche and a shareholder of the Roche Group. KHK has served as speaker, consultant, and advisory member for or has received research funding from AbbVie, Amgen, Enorasis, Epsilon Health, Dr Falk Pharma, Faran Ferring, Genesis, Grifols, Janssen, Koper, MSD, Mylan, Shire, Takeda, and Vianex. MLH has received investigator-initiated research grants from Tillotts, Ferring, Takeda, and Pfizer; advisory board honoraria from Takeda and AbbVie; and speaking fees from Takeda, AbbVie, Tillotts, Ferring, Galapagos, Janssen, and MSD. ZK has served as speaker for AbbVie, Takeda, Janssen, Freseinus, and Oktal Pharma/Celltrion. MC has served as a speaker, as a consultant, or has received research or education funding from MSD, AbbVie, Hospira, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr Falk Pharma, Tillotts Pharma, Biogen, Gilead, and Eli Lilly. EVL has received grants or contracts from AbbVie, Bristol Myers Squibb, Celgene/Receptos, Genentech, Gilead, Gossamer Bio, Janssen, Pfizer, Takeda, Theravance, and UCB; consulting fees from AbbVie, Amgen, Arena, Boehringer Ingelheim, Bristol Myers Squibb, Calibr, Celgene, Fresenius Kabi, Genentech, Gilead, Gossamer Bio, Janssen, Iterative Scopes, Ono Pharma, Pfizer, Protagonist, Scipher Medicine, Surrozen, Takeda, and UCB; reports the following patents: USA 11 249 084 (issued), USA 10 041 948 (issued), and USA 17 668 915 (pending); has participated on a data safety monitoring board or advisory board for Eli Lilly and Morphic; owns stock in Exact Sciences; and is a board member of Crohn's & Colitis Foundation, Minnesota-Dakotas Chapter. PLL has been a speaker or advisory board member, or both, for AbbVie, Amgen, BioJamp, Bristol Myers Squibb, Fresenius Kabi, Genentech, Gilead, Janssen, Merck, Mylan, Organon, Pendopharm, Pfizer, Roche, Takeda, Tillots, and Viatris, and has received unrestricted research grants from AbbVie, Gilead, Takeda, and Pfizer. JPG has served as a speaker, consultant, and advisory member for or has received research funding from MSD, AbbVie, Pfizer, Kern Pharma, Biogen, Mylan, Takeda, Janssen, Roche, Sandoz, Celgene/Bristol Myers Squibb, Gilead/Galapagos, Eli Lilly, Ferring, Faes Farma, Shire Pharmaceuticals, Dr Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Norgine, and Vifor Pharma. WB has received research grants from Vifor Pharma and B Braun Medical; consulting fees from Takeda and B Braun Medical; speaker fees from Medtronic, Takeda, B Braun Medical, and Johnson & Johnson; and is a stock owner of Semiflex Company. RBG has received grants or contracts from AbbVie and Janssen; consulting fees from AbbVie; and honoraria for lectures from AbbVie and Cornerstone Health. MDK has received grants or contracts from Pfizer, Takeda, Janssen, AbbVie, Eli Lilly, Genentech, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, and Arenapharm; consulting fees from Takeda and Pfizer; speaker fees from AbbVie; has participated on data safety monitoring board or advisory board for Eli Lilly; and owns stock in Johnson & Johnson. MJP has received grants or contracts from Takeda, Janssen, Galapagos, Tramedico, MSD, Takeda, Janssen, and Bristol Myers Squibb; honoraria for lectures from Bristol Myers Squibb, Janssen, AbbVie, and Galapagos; consulting fees from Janssen and Gilead; and has a leadership or fiduciary role in the MyCoach foundation. JMA has served as speaker, consultant, and advisory member for AbbVie, Allergan, Anatara, Atmo Capsule, Bayer, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Ferring Fresenius Kabi, Gilead, Hospira, Immuninc, ImmunsanT, Janssen, MSD, Nestle, Novartis, Pfizer, Sandoz, Shire, Takeda, and Vifor; has participated on a data safety monitoring board or advisory board for Janssen; has received research grants from the Royal Adelaide Hospital research fund, The Hospital Research Fund 2020–22, and The Helmsley Trust 2020–23. SCN has received grants or contracts from AbbVie, Ferring, and Olympus and Janssen; consulting fees from AbbVie, Pfizer, Ferring, and Janssen; honoraria for lectures from AbbVie, Ferring, Janssen, Menarini, Takeda, Tillotts and Pfizer; has participated on a data safety monitoring board or advisory board for AbbVie, Pfizer, Ferring, and Janssen; is a shareholder of GeniBiome; and is a director of the Microbiota I-Center, Hong Kong. HOM has received research grants from Takeda and Biogen, consulting fees from Takeda, and speaking fees from Pfizer and Biogen. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Emerging data suggest that a treat-to-target approach and early therapeutic intervention using regular objective disease assessment leads to improved outcomes. Our aim was to evaluate the value of objective disease monitoring during regular follow-up in a single tertiary inflammatory bowel disease center., Methods: Consecutive inflammatory bowel disease patients (n = 161, Crohn's disease: 118/ulcerative colitis: 43; biological therapy: 70%) were included and followed up for 1 year between January and December 2018. Data on clinical disease activity, biomarkers, endoscopy, imaging, outpatient visits, treatment optimization, hospitalization, and surgery were collected. We compared the monitoring strategy according to the clinical activity (remission/flare/post-flare/continuous activity) every 3 months (assessment period)., Results: In total, n = 644 assessment periods were evaluated. Biomarkers were evaluated in 82.9%-83.9% of patients in each assess ment period regardless of clinical activity. Colonoscopy was more frequently performed in active disease (flare/continuous disease activ ity: 21.1%/18.9% vs. clinical remission: 10.1% per assessment period). Magnetic resonance imaging was performed in 7.7%-16.7%/ period in Crohn's disease patients, while the use of computed tomography was low (2.4%/period) and mainly performed in active dis ease. Treatment optimization was more frequent in patients with active disease (biological start/dose optimization: 31.1%/33.8%/ period, steroid start: 13.2%/period). Patients with continuous activity (2.62), flare (2.45), and post-flare (2.05) had higher mean patient visit counts compared to remission (1.68/period)., Conclusions: Objective monitoring strategy was applied with routine assessment of clinical activity and biomarkers. Fast-track colo noscopic evaluations were adapted to the clinical stage of the disease while screening colonoscopies and magnetic resonance imaging were frequently used. Objective monitoring resulted in the early optimization of medical therapy and frequent specialist follow-up visits.

Introduction: The aim of this study is to estimate the risk of major adverse cardiovascular events (MACEs) in adult patients with inflammatory bowel disease (IBD) treated with biologic therapies and small molecules., Methods: Databases were searched up to July 2022 to identify eligible studies that assessed the risk of MACEs in patients (age≥18 years) with IBD treated with biologic therapies and small molecules. Primary outcome was the rate of MACEs observed in patients receiving biologic or small molecules therapies during induction and maintenance phases of RCTs., Results: In total 64 studies were included in the analysis. 22 RCTs involving 12,196 patients with Crohn's disease (CD) were included and 32 RCTs involving 22,007 patients with ulcerative colitis (UC). In patients with CD, risk of MACE was not higher than placebo during induction or maintenance phases, infliximab (OR 0.63, 95% CI 0.07-6.14) and ustekinumab (OR 0.50, 95% CI 0.03-8.04). In patients with UC, risk of MACE was not higher than placebo, tofacitinib (OR 1.30, 95% CI 0.15-11.21) and upadcitinib (OR 0.50, 95% CI 0.03-7.97) during induction or maintenance., Conclusion: The use of biologic therapies and small molecules among adult patients with IBD had no significant impact on the risk of MACEs during induction and maintenance period of RCTs. Real world data is warranted to assess long-term risks.

Background: Data from population-based studies investigating trends in environmental factors associated with inflammatory bowel disease (IBD) is lacking. We aimed to assess long-term time trends of environmental and socioeconomic factors in IBD patients from a well-defined population-based cohort from Veszprem, Hungary., Methods: Patients were included between 1 January 1977, and 31 December 2020. Trends of environmental and socioeconomic factors were evaluated in three periods based on the decade of diagnosis, representing different therapeutic eras: cohort-A,1977-1995; cohort-B,1996-2008 (immunomodulator era); and cohort-C, 2009-2020 (biological era)., Results: A total of 2240 incident patients with IBD were included (ulcerative colitis (UC) 61.2%, male 51.2%, median age at diagnosis: 35 years (IQR 29-49)). Rates of active smoking significantly decreased over time in Crohn's disease (CD): 60.2%, 49.9%, and 38.6% in cohorts A/B/C ( p < 0.001). In UC, the rates were low and stable: 15.4%, 15.4%, and 14.5% in cohorts A/B/C ( p = 0.981). Oral contraceptive use was more common in CD compared to UC (25.0% vs. 11.6%, p < 0.001). In UC, prevalence of appendectomy before diagnosis decreased over time: 6.4%, 5.5%, and 2.3% in cohorts A/B/C ( p = 0.013). No significant changes were found in the socio-geographic characteristics of the IBD population (urban living: UC, 59.8%/64.8%/ 62.5% ( p = 0.309) and CD, 62.5%/ 62.0%/ 59.0% ( p = 0.636), in cohorts A/B/C). A greater percentage of patients had completed secondary school as the highest education level in later cohorts in both UC (42.9%/50.2%/51.6%, p < 0.001) and CD (49.2%/51.7%/59.5%, p = 0.002). A higher percentage of skilled workers (34.4%/36.2%/38.9%, p = 0.027) was found in UC, but not in CD ( p = 0.454)., Conclusion: The association between trends of known environmental factors and IBD is complex. Smoking has become less prevalent in CD, but no other major changes occurred in socioeconomic factors over the last four decades that could explain the sharp increase in IBD incidence.

Background and Aims: The number of population-based studies in ulcerative colitis [UC] from Eastern Europe is limited. Our aim here was to analyse the incidence, prevalence, disease phenotype, treatment strategy, disease course and colectomy rates in a prospective population-based inception cohort including UC patients diagnosed between 2007 and 2018. The present study is a continuation of the Veszprem IBD cohort since 1977., Methods: In total, 467 UC patients were included [male/female: 236/231; median age at diagnosis: 36 years, IQR: 25-54 years]. Both in-hospital and outpatient records were collected and comprehensively reviewed. The mean length of follow-up was 8.34 ± 3.6 years. Demographic data were derived from the Hungarian Central Statistical Office., Results: The mean incidence rate was 11.02/105 person-years in this 12-year period. Prevalence was 317.79/105 persons in 2015. Disease extent at diagnosis was proctitis [E1] in 22.3%, left-sided colitis [E2] in 43.9% and extensive colitis [E3] in 33.8%. The probability of disease extent progression was 11.6% [SE: 1.8] after 5 years. The distribution of maximal therapeutic steps was 5-ASA in 46.9%, corticosteroids in 16.3%, immunosuppressives in 19.3% and biologicals in 16.5%. The probability of receiving biological therapy after diagnosis was 9.9% [SE: 1.4] at 3 years. The overall colectomy rate was 4.1% in the population. The probability of colectomy was 1.5% [SE: 0.6] at 1 year, 3.6% [SE: 0.9] at 5 years and 4.4% [SE: 1.0] at 10 years., Conclusions: The incidence of UC was high in Hungary, similar to high-incidence areas in Western Europe. Treatment strategies are in line with the biological era. The probability of progressing to proximal disease, and the medium- and long-term colectomy rates were both lower compared with data from Western European centres., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Patients with inflammatory bowel disease (IBD) have an increased risk of cancer secondary to chronic inflammation and long-term use of immunosuppressive therapy. With the aging IBD population, the prevalence of cancer in IBD patients is increasing. As a result, there is increasing concern about the impact of IBD therapy on cancer risk and survival, as well as the effects of cancer therapies on the disease course of IBD. Managing IBD in patients with current or previous cancer is challenging since clinical guidelines are based mainly on expert consensus. Evidence is rare and mainly available from registries or observational studies. In contrast, excluding patients with previous/or active cancer from clinical trials and short-term follow-up can lead to an underestimation of the cancer or cancer recurrence risk of approved medications. The present narrative review aims to summarize the current evidence and provide practical guidance on the management of IBD patients with cancer.

Background and Aims: The number of prospective population-based studies on Crohn's disease[CD] is still limited from Eastern Europe. The present study is a continuation of the Veszprem IBD cohort. Our aim was to analyse incidence, prevalence, disease phenotype, treatment strategy, disease course, and surgical outcomes in a prospective population-based inception cohort including CD patients diagnosed between 2007 and 2018., Methods: A total of 421 consecutive inception patients were included [male/female:237/184; mean age at diagnosis: 33.3 ± 16.2years]. Both in-hospital and outpatient records were collected and comprehensively reviewed. Demographic data were derived from the Hungarian Central Statistical Office., Results: Mean incidence rate was 9.9 [95% CI: 9.0-10.9]/105 person-years in this 12-year period. Prevalence rate was 236.8 [95% CI: 220.8-252.8] in 2015; 17.6% and 20.0% of the patients had stenosing[B2] and penetrating[B3] disease behavior at diagnosis,respectively. The probability of disease behaviour progression from luminal to B2/B3 phenotype was 14.7% (standard error [SE]: 2.2) at 5 years after diagnosis. Distribution of maximal therapeutic steps during the total follow-up (8.5 years [8.5y], standard deviation [SD]: 3.3) was 5-aminosalicylic acid [5-ASA] in 15.7%, corticosteroids in 14.3%, immunosuppressives in 42.5%, and biologic therapy in 26.2%. The probability of receiving biologictherapy after diagnosis was 20.9% [SE: 2.0] at 5 years. The probability of first resective surgery was 20.7% [SE: 2.0] at 1 year, 26.1% [SE: 2.2] at 5 years, and 30.7% [SE: 2.4] at 10 years. The perianal surgery rate was 31.3% among patients with perianal involvement., Conclusions: The incidence of CD in Hungary was high, similar to high-incidence areas in Western Europe. Treatment strategies are reflecting the biologic era. Disease behaviour progression was lower, as well as long-term [10y] surgery rates decreasing compared with data from previous decades., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with cardiovascular disease in the general population. Both conditions seem more frequent in patients with inflammatory bowel disease (IBD). We aimed to assess the effect of NAFLD and liver fibrosis on intermediate-high cardiovascular risk in IBD., Methods: We prospectively included IBD patients undergoing a routine screening program for NAFLD by transient elastography (TE) with associated controlled attenuation parameter (CAP). NAFLD and significant liver fibrosis were defined as CAP ≥275 dB m -1 and liver stiffness measurement by TE ≥8 kPa, respectively. Cardiovascular risk was assessed with the atherosclerotic cardiovascular disease (ASCVD) risk estimator and categorized as low if <5%, borderline if 5%-7.4%, intermediate if 7.5%-19.9%, and high if ≥20% or if previous cardiovascular event. Predictors of intermediate-high cardiovascular risk were investigated by multivariable logistic regression analysis., Results: Of 405 patients with IBD included, 278 (68.6%), 23 (5.7%), 47 (11.6%), and 57 (14.1%) were categorized as at low, borderline, intermediate, and high ASCVD risk, respectively. NAFLD and significant liver fibrosis were found in 129 (31.9%) and 35 (8.6%) patients, respectively. After adjusting for disease activity, significant liver fibrosis and body mass index, predictors of intermediate-high ASCVD risk were NAFLD (adjusted odds ratio [aOR] 2.97, 95% CI, 1.56-5.68), IBD duration (aOR 1.55 per 10 years, 95% CI, 1.22-1.97), and ulcerative colitis (aOR 2.32, 95% CI, 1.35-3.98)., Conclusions: Assessment of cardiovascular risk should be targeted in IBD patients with NAFLD, particularly if they have longer IBD duration and ulcerative colitis., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Introduction: Chronic cytomegalovirus (CMV) infection is very frequent in people living with HIV (PLWH). High anti-CMV IgG titres, which may be linked to transient CMV replication, have been associated with earlier mortality, CD8 T-cell expansion, lower CD4/CD8 ratio and increased T-cell senescence. We previously showed that anti-CMV IgG titres correlated with gut permeability in PLWH on antiretroviral therapy (ART), which was associated with microbial translocation, systemic inflammation and non-infectious/non-AIDS comorbidities. Letermovir, a novel anti-CMV drug with a good safety profile, was recently approved for anti-CMV prophylaxis in allogeneic haematopoietic stem cell transplant recipients. A drastic and selective reduction of both low-grade replication and clinically significant CMV infections, combined with an improved immune reconstitution have been reported. In vitro , letermovir prevented CMV-induced epithelial disruption in intestinal tissues. Based on these findings, we aim to assess whether letermovir could inhibit CMV subclinical replication in CMV-seropositive PLWH receiving ART and, in turn, decrease CMV-associated gut damage and inflammation., Method and Analysis: We will conduct a multi-centre, open-label, randomised, controlled clinical trial, including a total of 60 CMV-seropositive ART-treated PLWH for at least 3 years, with a viral load <50 copies/mL and CD4 + count >400 cells/µL. Forty participants will be randomised to receive letermovir for 14 weeks and 20 participants will receive standard of care (ART) alone. Plasma, pheripheral blood mononuclear cells (PBMCs), and stool samples will be collected. Colon biopsies will be collected in an optional substudy. We will assess the effect of letermovir on gut damage, microbial translocation, inflammation and HIV reservoir size., Ethics and Dissemination: The study was approved by Health Canada and the Research Ethics Boards of the McGill University Health Centre (MUHC-REB, protocol number: MP37-2022-8295). Results will be made available through publications in open access peer-reviewed journals and through the CIHR/CTN website., Trial Registration Number: NCT05362916., Competing Interests: Competing interests: LR is a post-doctoral fellow supported by the Swiss National Science Foundation (SNSF) and the CTN/CIHR. SI is a post-doctoral fellow from the Fonds de recherche du Quebec en santé, and from the CIHR/CTN. J-PR is the holder of the Louis Lowenstein Chair in Hematology and Oncology, McGill University. J-PR has performed contract research and/or served on Advisory Boards for Gilead Sciences Canada, Merck Canada, Abbvie, ViiV Healthcare, Bristol Myers Squibb, Janssen. NC has received research funding from EMD Serono and has served on the Advisory Board of Gilead Sciences Canada. AdP is a senior Clinical Research Scholar supported by Fonds de la recherche Quebec -Santé (FRQ-S). BL is a senior Clinical Research Scholar supported by FRQ-S and received consultancy fees and/or honoraria from Gilead, Merck, and ViiV, and obtained research funds from Gilead, Merck, and ViiV, and support to attend educational conferences from Viiv Healthcare and Gilead. CTC is supported by a Fonds de recherche du Québec-Santé (FRQS) Junior 2 career award and has received consultancy fees and/or honoraria from Gilead and ViiV, and obtained research funds from Gilead, Merck, and ViiV, and support to attend educational conferences from Viiv Healthcare and Gilead. NK reports research funding from Gilead Sciences, advisory fees from Gilead Sciences, ViiV Healthcare, Merck and Abbvie, and speaker fees from Gilead Sciences, Abbvie and Merck, all outside of the submitted work. NK is supported by a career award from the Fonds de Recherche Québec – Santé (FRQ-S; Junior 1). CTC is the Pfizer/Université de Montréal Chair on HIV translational research and has received consultancy fees and honoraria from Gilead, Merck, GSK, Astra-Zeneca, Medicago, Sanofi. This study is supported in part (study drug in-kind) by a research grant from Investigator-Initiated Studies Program of Merck Sharp & Dohme Corp. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme Corp., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Objective monitoring and effective early treatment using a treat-to-target approach are key to improving therapeutic outcomes in IBD patients. This study aimed to assess adherence to objective monitoring (clinical, biomarkers, and endoscopy) and its impact on clinical outcomes., Methods: A prospective, multicenter study included consecutive IBD patients starting on adalimumab therapy between January 2019 and December 2020. Disease activity, assessed by the Harvey-Bradshaw index (HBI), partial Mayo, C-reactive protein (CRP), fecal calprotectin (FCAL), and endoscopy were evaluated at adalimumab initiation and 3, 6, 9 and 12 months. Therapeutic drug monitoring, changes in treatment, drug sustainability, and clinical outcomes were assessed., Results: 104 IBD patients were enrolled (78.8% CD, median age 34.3 years, disease duration 9 years). During the 12 months follow-up, high adherence to clinical activity assessment was observed in both CD (81.3%- 87.7%) and UC patients (76.5-90.9%). CRP measurement decreased over time in both CD (37.3%-54.9%) and UC (29.4%-50.0%). The adherence to serial FCAL monitoring was low in CD (22.7-31.3%) and UC patients (17.6-56.0%). UC patients had higher adherence to early endoscopic assessment (<6 months) compared to CD patients (40.9% vs. 21.5%). Adherence to early combined clinical and biomarkers resulted in earlier dose optimization in CD and UC (log-rank<0.001), but drug sustainability was not different. The patients with early combined adherence had a significantly higher clinical remission rate at 1 year compared to non-adherence (70.2% vs. 29.8%, p=0.007) but no significant difference in UC patients., Conclusions: The adherence to early objective monitoring with combined clinical and biomarkers assessment in IBD patients starting adalimumab therapy led to dose optimization and improved 1-year clinical remission in CD but did not change drug sustainability and clinical remission in UC.