The goal of treatment for Crohn's disease (CD) is to achieve mucosal or transmural healing, and biomarker measurements are useful in monitoring disease activity and guiding treatment. This study aimed to investigate the utility of a new urinary biomarker, prostaglandin E-major urinary metabolite (PGE-MUM), in assessing CD activity.

The study involved 87 patients with CD who underwent endoscopic examination and measurements of 4 biomarkers: Prostaglandin E-major urinary metabolite, fecal calprotectin (FC), leucine-rich α2 glycoprotein (LRG), and C-reactive protein (CRP). Endoscopic activity was assessed by the Simple Endoscopic Score for Crohn's Disease (SES-CD). Correlations between the CD activity index (CDAI) and SES-CD with the 4 biomarkers were analyzed, and receiver-operating characteristic (ROC) analyses were performed to predict SES-CD ≧ 3.

All 4 biomarkers showed significant correlations with both CDAI and SES-CD. The cutoff (area under the curve [AUC]) values for predicting SES-CD ≥ 3 were as follows: PGE-MUM, 25.2 µg/g Cr (0.800); FC, 257 mg/kg (0.816); LRG, 11.8 µg/mL (0.748); and CRP, 0.22 mg/dL (0.656). Subgroup analysis revealed significant correlations between PGE-MUM and SES-CD in both the L1 (small intestine only) and L2 + L3 (including large intestine) groups, with correlation coefficients of 0.654 and 0.586, respectively. In the L1 group, ROC analysis revealed that, among the 4 biomarkers, PGE-MUM had the highest AUC for predicting SES-CD ≥ 3, with a cutoff (AUC) of 33.1 µg/g Cr (0.861).

PGE-MUM is a biomarker that can reflect endoscopic activity in patients with CD and may be particularly useful in small intestinal lesions.

Currently, medical therapy of Crohn's disease (CD) can reduce the progression of some forms of structural bowel damage (SBD), but it does not prevent it. Once SBD has developed, it is important to assess the potential of medical treatments to reverse this damage.

To determine whether transmural healing (TH), assessed by intestinal ultrasonography (IUS), can be achieved with medical treatment in CD patients with SBD compared to those without.

A prospective, longitudinal, observational study was conducted to compare IUS monitoring at 3 and 12 months of treatment between CD patients with SBD prior to treatment and those with an inflammatory pattern.

Three months after starting treatment, patients without SBD had a significantly higher TH rate than those with SBD (25.8% vs 7.8%, respectively; P = .004). However, after 12 months, the TH rate was not significantly higher in patients without SBD compared to those with SBD (34% vs 26.6%, respectively; P = .317). During these 12 months, the need for corticosteroids, hospitalizations, and surgical resection was significantly higher in the SBD group.

Biological treatment can reverse SBD in CD, but hospitalizations and surgery rates remain higher in this group.

Anti-TNFα antibodies are effective in controlling intestinal inflammation caused by Crohn's disease. However, many patients undergo surgery due to diminished efficacy of the antibodies during maintenance therapy. Currently, the decision between intensification of TNFα therapy and surgery is difficult to make. The purpose of this study was to determine the effect of preoperative treatment with anti-TNFα antibodies on postoperative recurrence of Crohn's disease. One hundred and fourteen consecutive patients with Crohn's disease who underwent bowel resection with anastomosis between 2009 and 2021 were retrospectively analyzed on the preoperative treatment history and perioperative information. Of the 74 patients who used anti-TNFα antibodies preoperatively, 43 underwent surgery after intensification of therapy following attenuation of anti-TNFα antibody efficacy. Time to postoperative endoscopic recurrence was significantly shorter in the group using anti-TNFα antibodies than in the group not using them (p = 0.0055). We found no difference in time to postoperative endoscopic recurrence between patients who underwent intensified therapy and those who underwent immediate surgery. Patients who received preoperative anti-TNFα antibody had a shorter time to postoperative endoscopic recurrence, but the presence or absence of intensified treatment after weakening of the anti-TNFα antibody effects did not affect the time to postoperative endoscopic recurrence.

Achieving deep remission, encompassing clinical, endoscopic, and biological remission, is the goal in managing Crohn's disease (CD). The role of histological remission (HR) remains unclear. This study aimed to examine the impact of histological inflammation on clinical relapse risk in CD and explore the relationship between histology, endoscopic scores, and biomarkers.

Patients from the prospective STORI (Stable Remission on Combined Therapy with Immunosuppressors) cohort underwent ileocolonoscopy with Crohn's Disease Endoscopic Index of Severity calculation and 2 biopsies from the most inflamed or previously inflamed areas. Histological scores (Robarts, Geboes, modified Geboes, Nancy, and IBD-DCA) were determined by 2 independent pathologists in a central reading process. Histological remission was defined by specific score thresholds. Clinical relapse, defined by Crohn's Disease Activity Index (CDAI) > 250 or a CDAI increase of 70 points over 2 weeks, was monitored for at least 1 year.

Out of 115 patients included in STORI, 160 biopsies (44 ileal and 116 colonic) from 76 patients were analyzed. Histological remission rates were 46% (Nancy), 55% (Robarts), 61% (Geboes), and 41% (IBD-DCA). During follow-up, 35 patients (46%) experienced a clinical relapse: 37% with HR and 56% without, based on the Nancy score. Among the mucosal healing subgroup (45 patients), 34% with HR, and 44% without relapsed (p = 0.18). Histological scores did not predict clinical relapse. Only fecal calprotectin was a significant predictor in multivariate analysis (p = 0.029).

Despite correlations with endoscopy and biomarkers, histological scores did not predict clinical relapse in CD patients in remission. Thus, these scores are not recommended for clinical practice to assess relapse risk in CD.

Gastrointestinal ultrasound (GIUS) is recommended for monitoring Crohn's disease (CD). GIUS scores are used to quantify CD activity. Among them, International Bowel Ultrasound Segmental Activity Score (IBUS-SAS), Bowel Ultrasound Score (BUSS), Simple Ultrasound Score, and Simple Ultrasound Score for Crohn's Disease are most commonly used. The aim of this study was to compare and correlate the performance of such indicators with endoscopic activity and to calculate interobserver agreement.

Consecutive patients with CD at our hospital between June 2015 and July 2021 were retrospectively enrolled. All patients underwent ileocolonoscopy after medical treatment. GIUS was performed within 2 weeks, and 4 GIUS scores were independently calculated. Receiver operating characteristic curve analyses were used to determine a cutoff value. Cohen kappa (κ) coefficient was calculated to estimate the agreement between GIUS findings.

A total of 106 patients with CD were enrolled. 80.2% (85/106) were endoscopic active (Simple Endoscopic Score for Crohn's disease ≥3), and 8.49% (9/106) were severe cases (Simple Endoscopic Score for Crohn's disease ≥9). All GIUS features (bowel wall thickness, color Doppler signs, bowel wall stratification, inflammatory signals at the mesentery) were statistically significant in assessing CD activity ( P < 0.05). IBUS-SAS showed the highest area under the curve (0.98; 95% CI: 0.96-1.00) and specificity (95.2%) for a cutoff value of 46.50. However, IBUS-SAS had only moderate agreement (Cohen κ = 0.427; P < 0.001). BUSS had substantial interobserver agreement (Cohen κ = 0.947; P < 0.001), with a similar diagnostic value (sensitivity, 100.0%; accuracy, 95.3%; area under the curve of 0.96 [95% CI: 0.91-1.00] for a cutoff value of 4.58).

GIUS score is an efficient and reliable method to assess CD activity. BUSS achieved a high accuracy and excellent interobserver agreement, which is more suitable for treatment assessment.

Imaging is essential in assessing patients with Crohn's disease, and it provides important and complementary information to the clinical and endoscopic findings. Patients can be accurately phenotyped and complications identified.

Background: A significant concern for patients with Inflammatory Bowel Disease (IBD) is predicting and managing disease flares. While healthcare providers rely on biomarkers, providing conclusive patient advice remains challenging. This review explores the role of lifestyle, psychological health, and environmental exposures in the prediction and management of IBD flares. Methods: This review followed PRISMA guidelines (2020). A structured search was conducted in PubMed for articles published between 2012 and 2024, using free and Medical Subject Heading (MeSH) terms for predicting factors in IBD. Inclusion criteria included studies reporting primary data on modifiable clinical or environmental predictors of IBD relapse, excluding studies on post-operative investigations, treatment cessation, and pediatric or pregnant populations. The Mixed Method Appraisal Tool (MMAT) was used to assess the quality of the studies. Results: Out of 2287 identified citations, 58 articles were included. Several modifiable factors influencing disease flares were identified, including psychological stress, sleep disturbances, smoking, and nutrition. Poor sleep quality and mental health were linked to increased flare risks, while smoking was associated with higher relapse rates in Crohn's disease. Environmental exposures, such as heat waves and high-altitude regions, also contributed. Predictive models integrating clinical, lifestyle, and psychological factors showed promising accuracy but require further refinement. Limitations of this review include the potential for publication bias, variability in flare definitions, and limited sample sizes Conclusions: Key predictors of IBD flares include dietary factors, psychological stress, poor sleep quality, and pharmacological influences. Personalized approaches integrating these predictors can optimize disease control and improve patient outcomes.

Criteria for "difficult-to-treat" inflammatory bowel disease (DTT-IBD) have recently been proposed to standardize terminology. We aimed to evaluate the prevalence, characteristics, management, and outcomes of DTT-IBD.

We conducted a retrospective study in 2 tertiary centers in Italy.

Among 1736 IBD patients treated with biologics/advanced small molecules, 430 (24.8%) met at least 1 DTT-IBD criterion, of which 331 (77%) failed at least 2 mechanisms of action. In ulcerative colitis (UC), left-sided and extended colitis were risk factors for DTT compared to proctitis (odds ratio [OR] 6.55; 95% confidence interval [CI], 1.93-40.98; p = 0.011 and OR 10.12; 95% CI, 3.01-63.14; p = 0.002, respectively). In Crohn's disease (CD), multiple localizations (L3+L4) (OR 3.04; 95% CI, 1.09-8.34; p = 0.03), stricturing (OR 2.24; 95% CI, 1.52-3.34; p < 0.001), and penetrating (OR 2.33; 95% CI, 1.55-3.53; p < 0.001) behaviors, and perianal disease (OR 2.49; 95% CI, 1.75-3.53; p < 0.001) were the main risk factors for DTT. Delay in advanced treatment initiation was positively associated with DTT-CD (OR 1.74; 95% CI, 1.27-2.41; p = 0.001) but protective in UC (OR 0.65; 95% CI, 0.45-0.93; p = 0.019). The rates of symptomatic, biochemical, and endoscopic remission were lower in DTT-IBD compared to non-DTT-IBD. The difference was most evident for endoscopic remission (25% vs 62%). Drug persistency in each following line of treatment progressively decreased in CD and UC. All advanced drugs used in DTT-IBD had similar persistence.

DTT-IBD was prevalent in approximately one-quarter of patients with IBD in a tertiary care setting. Certain IBD phenotypes and the delay in initiating treatment in CD were risk factors for DTT. Drug persistency decreased progressively with every subsequent line of therapy.

The course of Crohn's disease (CD) is highly variable. The Prospektive Evaluation eines Score zur Vorhersage eines milden Verlaufsbei neu diagnostizierten Morbus Crohn-Patienten in gastroenterologischen Fachpraxen (PROGNOS) study aimed to determine the frequency of a mild disease course and validate a proposed prediction score.

The PROGNOS study is a prospective study of CD patients who were newly diagnosed and, except for 1 course of 5-aminosalicylic acid or steroids for ≤10 days, therapy-naïve. Among other predefined inclusion criteria, the initial diagnosis had to be made ≤6 weeks before enrollment. All inception cohort patients were diagnosed and screened consecutively in participating gastroenterology practices in Germany specialized in inflammatory bowel disease. All screened CD patients were scored and, if possible, included in the study for up to 5 years (NCT02193048).

A total of 201 CD patients were included in the study (43.3% male; mean age 33 years, mean follow-up 38 months). Altogether, 29.5% of the patients had a mild course at 36 months. Among those with a score ≤2, therapy escalation at 36 months was necessary for only 24.2%, whereas in the group with a score >2, therapy escalation was necessary for 70.2% of patients. In the Kaplan-Meier curve showing time to therapy escalation in the 2 groups, there was a pronounced and statistically significant divergence of the curves starting at 3 months and extending to 48 months (P < .001).

In this prospective study, about 30% of incident CD patients had a mild disease course. Our suggested PreMiCC (prediction score for a mild course of Crohn's disease) successfully predicted this.

Crohn's disease (CD) negatively impacts quality of life, and a high percentage of patients will need surgery. Ileocecal resection (ICR) is the most common abdominal procedure performed in CD. Postoperative complications are frequent, and recurrence is common. The main objectives of this study were to analyze risk factors (RF) for anastomotic leakage (AL) and recurrence after ICR, as well as quality of life (QoL) in CD in a sample of the Spanish population.

A prospective, multicenter, observational study was designed, including all types of hospitals in Spain from 2018 to 2021. Demographic and medical-surgical characteristics, postoperative complications, hospital types by annual ICR volume, and quality of life (IBDQ-9) up to 1 year follow-up (OYF) were recorded and analyzed.

A total of 386 ICRs were recorded. At 60 days, there were 134 (36.4%) complications, 46 (11.91%) of which were major. A total of 23 (5.9%) AL were registered, and RF were Montreal A3 [OR 14.2, 95% CI (2.70-126), p = 0.005], Montreal p [OR 7.29, 95% CI (1.14-44.4), p = 0.029], and intensified adalimumab treatment [3.8, 95% CI (1.2-13.1), p = 0.026]. Recurrences at OYF were 67 (19%), and RF were history of neoplasia [OR 7.14, p = 0.01], Montreal B3 [OR 2.12, p = 0.02], and minimally invasive surgery (MIS) [OR 2.63, p = 0.02]. The mean difference in IBDQ-9 from baseline to 60 days was +1.72 (n = 177, p < 0.001) and to OYF +2.12 (n = 140, p < 0.001).

The AL rate was 5.9%. Montreal A3, perianal disease, and intensified adalimumab were associated with a higher rate of AL. The recurrence rate was 17.6% (OYF). Prior neoplasia, Montreal B3, and MIS were associated with higher risk of recurrence. ICR improves quality of life at 60 days and is maintained 1 year after surgery.

A treat-to-target strategy for inflammatory bowel disease (IBD) recommends iterative treatment adjustments to achieve clinical and endoscopic remission. In asymptomatic patients with ongoing endoscopic activity, the risk/benefit balance of this approach is unclear, particularly with prior exposure to advanced therapies.

Using the RAND/University of California Los Angeles Appropriateness Method, 9 IBD specialists rated appropriateness of changing therapy in 126 scenarios of asymptomatic patients with ulcerative colitis and Crohn's disease and active endoscopic disease. Disease extent and behavior, prior treatment, prior complications, and recent disease progression were considered, as were factors that might influence decision-making, including age and pregnancy. Ratings were collected through anonymous survey, discussed at an in-person meeting, and finalized in a second anonymous survey.

Panelists rated change in therapy as appropriate (i.e., expected benefit sufficiently outweighs potential harms from continuing therapy) in 96/126 scenarios, generally in patients with progressive, complicated, and/or extensive disease, while changing therapy was rated uncertain in 27 scenarios of mild and/or stable disease. Changing therapy was rated inappropriate in ulcerative colitis patients with mild and stable disease previously exposed to ≥3 therapies or with improved endoscopic activity, and in Crohn's disease patients with only scattered aphthous ulcers. The validated threshold for disagreement was not crossed for any scenario. Patient age older than 65 years and a plan for pregnancy in the next year might influence decision-making in some settings.

Appropriateness ratings can help guide clinical decision-making about changing therapy to achieve endoscopic remission in asymptomatic patients with IBD until data from ongoing randomized studies are available.

Crohn's disease (CD) is a progressive, destructive, and disabling disorder. Our study aimed to assess changes over time in the Lémann index (LI) and the Inflammatory Bowel Disease Disability Index (IBD-DI) in a cohort of CD patients.

This was a single-center prospective cohort study of 130 consecutive CD patients with a follow-up of at least 4 years. The LI 1 and the IBD-DI 1 questionnaires were assessed in 2016 and again between September 2020 and October 2021 (LI 2 and IBD-DI 2).

Of the 130 patients with assessment of both LI 1 and IBD-DI 1, 61 had calculation of the LI 2 and 98 patients answered the IBD-DI 2 questionnaire, with a median time between the 2 evaluations of 4.2 years. The LI increased for 16 (26%), decreased for 26 (43%), and remained unchanged for 19 (31%) patients. The median LI did not change over time (9.6 vs 9.3; P = .14). Clinical disease activity was significantly associated with bowel damage progression. A high initial LI (>7.9) was not associated with CD progression (surgery, drug dose escalation, or change of biologic). The IBD-DI decreased for 59 (60.2%), increased for 37 (37.8%), and remained unchanged for 2 (2%) patients. The median IBD-DI decreased significantly over time (23.2 vs 21.4; P = .006). There was no correlation between the 2 indexes.

This is the first prospective cohort study assessing changes over time in both the LI and the IBD-DI in CD patients. After 4 years, the LI appeared to be stable and the IBD-DI decreased, with no correlation between the 2 indexes.

Pediatric Crohn's disease (CD) easily progresses to an active disease compared with adult CD, making it important to predict and minimize CD relapses. However, prediction of relapse at various time points (TPs) during pediatric CD remains understudied. We aimed to develop a real-time aggregated model to predict pediatric CD relapse in different TPs and time windows (TWs).

This retrospective study was conducted on children diagnosed with CD between 2015 and 2022 at Severance Hospital. Laboratory test results and demographic data were collected starting at 3 months after diagnosis, and cohorts were formed using data from 6 different TPs at 1-month intervals. Relapse-defined as a pediatric CD activity index ≥ 30 points-was predicted, and TWs were 3-7 months with 1-month intervals. The feature importance of the variables in each setting was determined.

Data from 180 patients were used to construct cohorts corresponding to the TPs. We identified the optimal TP and TW to reliably predict pediatric CD relapse with an area under the receiver operating characteristic curve score of 0.89 when predicting with a 3-month TW at a 3-month TP. Variables such as C-reactive protein levels and lymphocyte fraction were found to be important factors.

We developed a time-aggregated model to predict pediatric CD relapse in multiple TPs and TWs. This model identified important variables that predicted relapse in pediatric CD to support real-time clinical decision making.

Vedolizumab is a gut-selective anti-lymphocyte trafficking biologic indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD) in Canada.

The objective of this study was to evaluate the cost effectiveness of treatment sequencing for UC and CD from a public healthcare payer perspective, leveraging new real-world evidence from the literature and the EVOLVE study, a retrospective chart review.

Using separate decision tree/Markov models to assess cost effectiveness for UC and CD, two sequencing approaches were estimated for adult patients (≥ 18 years) diagnosed with UC or CD who were biologic-naïve: vedolizumab as first-line biologic followed by anti-tumor necrosis factor (TNF)-α versus first-line anti-TNFα followed by vedolizumab. Treatment effectiveness (response and remission), surgery rates, dose escalation and regain of response and safety inputs were estimated from EVOLVE, a retrospective chart review of real-world data, and evidence synthesis from the literature, whereas costs and utilities were estimated from health technology assessment reports, clinical trials, and the literature. Biosimilar costs were used for anti-TNFα. Both models simulated a 5-year time horizon and discounted costs and outcomes at 1.5%. Probabilistic base-case analyses (n = 10,000) reported total costs (2023 Canadian dollars) and quality-adjusted life-years (QALYs). Several scenario analyses were conducted to explore robustness of results.

In UC, vedolizumab as a first-line biologic followed by anti-TNFα resulted in an incremental gain of 0.09 QALYs (2.46 vs. 2.55) and saved $7179 ($134,028 vs. $126,848), making this a dominant strategy compared with first-line anti-TNFα followed by vedolizumab. In CD, use of vedolizumab as a first-line biologic resulted in an incremental gain of 0.04 QALYs (3.35 vs. 3.39) at an incremental cost of $50,631 ($89,850 vs. $140,381) versus first-line anti-TNFα followed by vedolizumab (incremental cost-effectiveness ratio of $1,265,775 per QALY).

Based on this analysis, sequencing vedolizumab as a first-line biologic prior to anti-TNFα in UC and CD provided additional clinical benefit to patients. In UC, vedolizumab as a first-line biologic also saved healthcare system costs compared with anti-TNFα, whereas in CD, vedolizumab provided incremental benefit at an incremental cost, which was not considered cost effective at a threshold of $50,000/QALY.

Endoscopy, histology, and cross-sectional imaging serve as fundamental pillars in the detection, monitoring, and prognostication of inflammatory bowel disease (IBD). However, interpretation of these studies often relies on subjective human judgment, which can lead to delays, intra- and interobserver variability, and potential diagnostic discrepancies. With the rising incidence of IBD globally coupled with the exponential digitization of these data, there is a growing demand for innovative approaches to streamline diagnosis and elevate clinical decision-making. In this context, artificial intelligence (AI) technologies emerge as a timely solution to address the evolving challenges in IBD. Early studies using deep learning and radiomics approaches for endoscopy, histology, and imaging in IBD have demonstrated promising results for using AI to detect, diagnose, characterize, phenotype, and prognosticate IBD. Nonetheless, the available literature has inherent limitations and knowledge gaps that need to be addressed before AI can transition into a mainstream clinical tool for IBD. To better understand the potential value of integrating AI in IBD, we review the available literature to summarize our current understanding and identify gaps in knowledge to inform future investigations.

Inflammatory bowel disease (IBD) is a progressive condition where ongoing inflammation in the gastrointestinal tract can lead to complications such as strictures, and fistulae. The long-term outcomes of newly diagnosed patients under current medical therapy can be used to plan health service provision and guide patients.

Prospective population-based data on all incident patients diagnosed with IBD in Canterbury was gathered in 2014 (n = 205). The medical records of these patients were followed for medication use, disease progression, hospitalization, surgery and mortality, in the 10 years since their diagnosis. Survival analysis and cox regression determined characteristics associated with earlier time to these outcomes.

Medical records of 184 IBD patients were able to be retrieved. Immunomodulators were used by 62% and biologics by 35%; hospitalization occurred for 42% and surgery for 15%. Montreal phenotype progression occurred for 21 and 7% of the cohort died. Younger age at diagnosis hazard ratio (HR) 2.1 (95% confidence interval [CI] 1.1-4.0) and Crohn's disease HR 1.7 (95% CI 1.1-2.6) was associated with immunomodulator use. Younger age was also associated with biologic use HR 2.9 (95% CI 1.2-6.9). Male gender was associated with surgery HR 2.8 (95% CI 1.2-6.4). Perianal disease at diagnosis (14.7%) was associated with immunomodulator use HR 2.58 (95% CI 1.44-4.59) and Montreal phenotype progression HR 2.93 (95% CI 1.10-7.77).

In the 10 years since diagnosis disease progression and treatment escalation occurred for most of this population-based cohort. Earlier intervention for patients with higher-risk characteristics may improve long-term outcomes reducing the burden on health systems.

The impact of ustekinumab (UST) on mucosal- and fistula healing and extraintestinal manifestations (EIM) in Crohn's disease (CD) were not fully elucidated in the registration trials. In this prospective, multicenter study (EudraCT number: 2017-005151-83) we evaluated the German label real-world-effectiveness of UST to achieve the primary endpoint of combined clinical and endoscopic response at week 52 and several secondary endpoints. Of 79 screened we enrolled 52 patients (female n = 28, bionaïve n = 13, biologic n = 39). At week 52 (per protocol analysis), 52% (n = 13/25) of patients achieved the primary endpoint [50% (n = 3/6) in the bionaïve, 45.5% (n = 5/11) biologic, 62.5% (n = 5/8 ) multiple biologics cohorts, respectively with age as independent predictor [OR 95% CI 0.933 (0.873, 0.998) p = 0.043], 60% (n = 15/25) achieved endoscopic response [50% (n = 3/6) in the bionaïve, 54.5% (n = 6/11) biologic, 75% (n = 6/8) multiple biologics cohorts, respectively], 36% (n = 9/25) achieved endoscopic remission [50% (n = 3/6) in the bionaïve, 27.3% (n = 3/11) biologic, 37.5% (n = 3/8) multiple biologics cohorts, respectively], 48% (n = 12/25) achieved mucosal healing [50% (n = 3/6) in the bionaïve, 36.4% (n = 4/11) biologic, 62.5% (n = 5/8) multiple biologics cohorts, respectively]. All achieved a fistula response and 33.3% (n = 1/3) in the multiple biologics group fistula remission at week 52. EIM decreased (week 0 28.2% vs. week 52 8%). CRP, FCP, PRO-2, EQ-5D-5L improved throughout. 36 patients (69.2%) experienced ≥ 1 treatment emergent adverse event, in 8 (15.4%) cases rated as severe and in 5 (9.6%) leading to UST discontinuation, but no very severe events or deaths. The effectiveness of UST was better than in the registration trials.

Histologic evaluation of mucosal healing in Crohn's disease is an evolving treatment target. We evaluated histologic outcomes for mirikizumab efficacy and associations with endoscopic and 1-year outcomes.

Biopsy specimens from 1 ileal and 4 colonic segments were evaluated at weeks 0, 12, and 52 from each of the 170 SERENITY participants. Criteria for the weeks 12 and 52 histologic response were no epithelial neutrophils or epithelial damage, or >50% decrease in either the Robarts Histopathology Index or the active Global Histologic Disease Activity Score, and remission (no mucosal neutrophils and no epithelial damage) had to be met in all biopsy specimens. Agreement was evaluated between histologic and endoscopic end points. Associations between 1-year outcomes and week 12 histologic and endoscopic response were evaluated.

At week 12, 1000 mg mirikizumab resulted in greater rates of histologic response (66% vs 27%; P < .001) and remission (26% vs 6%; P < .01) than placebo. Rates were numerically similar at 1 year (mirikizumab pooled response, 46%-69%; remission, 13%-31%). Agreement between week 12 histologic and endoscopic response was 69% (Cohen's kappa coefficient [κ] = 0.40) and remission was 83% (κ = 0.38) in all pooled arms, including placebo. At 1 year, the percentage of participants who received any dose of mirikizumab and achieved endoscopic remission differed by their week 12 response: histologic (20%), endoscopic (25%), combined histology-endoscopy (45%), or neither (4%) (P = .003).

In a post hoc analysis of phase 2 data, mirikizumab induced and sustained histologic response and remission in Crohn's disease over 52 weeks. Early combined histologic-endoscopic response was associated with endoscopic remission after 1 year of treatment with mirikizumab (ClinicalTrials.gov NCT02891226).

Inflammatory bowel disease (IBD) incidence has increased in the last decades due to changes in dietary habits. IBDs are characterized by intestinal epithelial barrier disruption, increased inflammatory mediator production and excessive tissue injury. Since the current treatments are not sufficient to achieve and maintain remission, complementary and alternative medicine (CAM) becomes a primary practice as a co-adjuvant for the therapy. Thus, the intake of functional food enriched in vegetal extracts represents a promising nutritional strategy. This study evaluates the anti-inflammatory effects of artichoke, caihua and fenugreek vegetal extract original blend (ACFB) in an in vitro model of gut barrier mimicking the early acute phases of the disease. Caco2 cells cultured on transwell supports were treated with digested ACFB before exposure to pro-inflammatory cytokines. The pre-treatment counteracts the increase in barrier permeability induced by the inflammatory stimulus, as demonstrated by the evaluation of TEER and CLDN-2 parameters. In parallel, ACFB reduces p65NF-κB pro-inflammatory pathway activation that results in the decrement of COX-2 expression as PGE2 and IL-8 secretion. ACFB properties might be due to the synergistic effects of different flavonoids, indicating it as a valid candidate for new formulation in the prevention/mitigation of non-communicable diseases.

Background: Crohn's disease (CD) is a chronic, progressive inflammatory condition, involving primarily the bowel, characterized by a typical remitting-relapsing pattern. Despite endoscopy representing the reference standard for the diagnosis and assessment of disease activity, radiological imaging has a key role, providing information about mural and extra-visceral involvement. Methods: Computed Tomography and Magnetic Resonance Imaging are the most frequently used radiological techniques in clinical practice for both the diagnosis and staging of CD involving the small bowel in non-urgent settings. The contribution of imaging in the management of CD is reported on by answering the following practical questions: (1) What is the best technique for the assessment of small bowel CD? (2) Is imaging a good option to assess colonic disease? (3) Which disease pattern is present: inflammatory, fibrotic or fistulizing? (4) Is it possible to identify the presence of strictures and to discriminate inflammatory from fibrotic ones? (5) How does imaging help in defining disease extension and localization? (6) Can imaging assess disease activity? (7) Is it possible to evaluate post-operative recurrence? Results: Imaging is suitable for assessing disease activity, extension and characterizing disease patterns. CT and MRI can both answer the abovementioned questions, but MRI has a greater sensitivity and specificity for assessing disease activity and does not use ionizing radiation. Conclusions: Radiologists are essential healthcare professionals to be involved in multidisciplinary teams for the management of CD patients to obtain the necessary answers for clinically relevant questions.

Rapidity of effect of advanced therapies for patients with Crohn's disease (CD) can be an essential decision parameter; however, comparative evaluation is lacking. We aimed to compare early response for advanced CD therapies in a network meta-analysis (NMA).

We searched systematically MEDLINE, Embase, and CENTRAL up to 19 February 2024, for randomised controlled trials. The co-primary outcomes were induction of clinical remission (Crohn's Disease Activity Index (CDAI) ≤150) and clinical response (≥100-point reduction in CDAI) within the first 6 weeks of treatment. We incorporated any assessment within this time point in a Bayesian random-effects NMA following PRISMA-NMA guidance (PROSPERO ID: CRD42022368509).

Twenty-five studies, comprising 7414 patients, were included. Infliximab combined with azathioprine or monotherapy ranked highest for induction of clinical remission within 6 weeks and was significantly superior to certolizumab, ustekinumab, guselkumab, vedolizumab, and upadacitinib. However, superiority over risankizumab 600 mg and adalimumab 160/80 mg was non-significant. Accordingly, infliximab in combination with azathioprine and guselkumab 600 mg ranked highest in the corresponding analysis of clinical response with no statistical significance demonstrated. Among bio-exposed patients, none of whom received infliximab, upadacitinib, and risankizumab induced the highest clinical responses. On the other hand, vedolizumab, certolizumab, and ustekinumab ranked lowest across the analyses.

We found infliximab to be ranked highest and superior to all other agents but risankizumab and adalimumab, demonstrating the highest probability of early induction of remission. Upadacitinib and risankizumab induced the highest clinical responses in bio-exposed patients. However, infliximab was not investigated in this population.

For some immune-mediated disorders, despite the range of therapies available there is limited evidence on which treatment sequences are best for patients and healthcare systems. We investigated how their selection can impact outcomes in an Italian setting.

A 3-year state-transition treatment-sequencing model calculated potential effectiveness improvements and budget reallocation considerations associated with implementing optimal sequences in ankylosing spondylitis (AS), Crohn's disease (CD), non-radiographic axial spondyloarthritis (NR-AxSpA), plaque psoriasis (PsO), psoriatic arthritis (PsA), rheumatoid arthritis (RA), and ulcerative colitis (UC). Sequences included three biological or disease-modifying treatments, followed by best supportive care. Disease-specific response measures were selected on the basis of clinical relevance, data availability, and data quality. Efficacy was differentiated between biologic-naïve and experienced populations, where possible, using published network meta-analyses and real-world data. All possible treatment sequences, based on reimbursement as of December 2022 in Italy (analyses' base country), were simulated.

Sequences with the best outcomes consistently employed the most efficacious therapies earlier in the treatment pathway. Improvements to prescribing practice are possible in all diseases; however, most notable was UC, where the per-patient 3-year average treatment failure was 37.3% higher than optimal. The results focused on the three most crowded and prevalent immunological sub-condition diseases in dermatology, rheumatology, and gastroenterology: PsO, RA, and UC, respectively. By prescribing from within the top 20% of the most efficacious sequences, the model found a 15.1% reduction in treatment failures, with a 1.59% increase in drug costs.

Prescribing more efficacious treatments earlier provides a greater opportunity to improve patient outcomes and minimizes treatment failures.

We aimed to determine whether Crohn's disease (CD) activity patterns assessed via a web-based symptom diary can help predict clinical outcomes in patients with newly diagnosed CD. Patients diagnosed with CD within the preceding 3 months were prospectively enrolled at four tertiary centers. All patients recorded their symptoms on a website using a smartphone at least once a week. The index outcomes were disease-related admission and surgery during follow-up. The disease activity from enrollment to outcome or last follow-up was reviewed for pattern analysis. Cox regression analysis was used to identify the predictors of disease outcomes. A total of 102 patients were enrolled. During a median follow-up period of 42 months, 25 (24.5%) and 6 (5.9%) patients required admission and surgery, respectively. Poor activity pattern was an independent predictor of disease-related hospitalization (adjusted hazard ratio [aHR], 3.96; 95% confidence interval [CI] 1.5-10.45; p = 0.005). A poor activity pattern (aHR, 19.48; 95% CI 1.86-203.95; p = 0.013) and female sex (aHR, 11.28; 95% CI 1.49-85.01; p = 0.018) were found to be independent predictors of bowel resection. CD disease activity patterns monitored through the mobile monitoring system may help predict clinical outcomes, such as disease-related hospitalization and surgery, in patients with newly diagnosed CD.

Disease Severity Index (DSI) provides comprehensive assessment of bowel damage (BD).

To evaluate DSI in patients with Crohn's disease (CD) at high risk of disease progression, compared to Lémann Index (LI).

Patients with CD in our center were reviewed consecutively between 2017 and 2019. DSI, LI, and complicated CD course were analyzed.

The median LI and DSI of included 300 patients were 1.63 (IQR 1.25-3.13) and 42 (IQR 32-51), respectively. 152 patients (50.7%) experienced a complicated disease course (median 5.1 months; IQR 1.1-20.2). DSI (AUC 0.66; 95% CI 0.60-0.72) better predicted a complicated course of CD over LI (AUC 0.56; 95% CI 0.50-0.63; P = 0.007). The cumulative probability of complicated CD course in severe patients was higher than those with 'mild CD' (P < 0.001). The Cox analysis identified DSI>43 (HR 2.18; 95% CI 1.54-3.09; P < 0.001), B2/3 vs. B1 (HR 2.80; 95% CI 1.99-3.94; P < 0.001), and a higher level of CRP (HR 1.01; 95% CI 1.00-1.02; P = 0.005) as independent prognostic factors for complicated CD. However, LI was not associated with complicated CD (P = 0.164).

Higher DSI was associated with complicated disease outcomes. DSI might play a better role than LI in identifying patients at high risks of disease progression.

The only biologic therapy currently approved to treat moderate to severe Crohn's disease in children (<18 years old) are those that antagonise tumour necrosis factor-alpha (anti-TNF). Therefore, it is critically important to develop novel strategies that maximise treatment effectiveness in this population. There is growing evidence that rates of sustained corticosteroid-free clinical remission, endoscopic healing and drug durability considerably improve when patients receive early anti-TNF dose optimisations guided by reactive or proactive therapeutic drug monitoring and pharmacodynamic monitoring. In response, our team has developed a personalised and scalable infliximab dosing intervention that starts with dose selection and continues throughout maintenance to optimise drug exposure. We hypothesise that a precision dosing strategy starting from induction and targeting dose-specific pharmacokinetic and pharmacodynamic endpoints throughout therapy will significantly improve outcomes compared with a conventional dosing strategy.

Conduct a clinical trial to assess rates of deep remission between Crohn's disease patients receiving infliximab with precision dosing (n=90) versus conventional care (n=90). Patients (age 6-22 years) will be recruited from 10 medical centres in the USA. Each centre has been selected to provide either precision dosing or conventional care dosing. Precision dosing includes the use of a clinical decision support tool (RoadMAB) from the start of infliximab to achieve specific (personalised) trough concentrations and specific pharmacodynamic targets (at doses 3, 4 and 6). Conventional care includes the use of a modified infliximab starting dose (5 or 7.5 mg/kg based on the pretreatment serum albumin) with a goal to achieve maintenance trough concentrations of 5-10 µg/mL. The primary endpoint is year 1 deep remission defined as a combination of clinical remission (paediatric Crohn's disease activity index<10 (child) or a Crohn's disease activity index<150 (adults)), off prednisone>8 weeks and endoscopic remission (simple endoscopic severity-Crohn's disease≤2).

). The study protocol has been approved by the Cincinnati Children's Hospital Medical Centre Institutional Review Board. Study results will be disseminated in peer-reviewed journals and presented at scientific meetings.

NCT05660746.

In inflammatory bowel disease (IBD), the loss of immune tolerance against gut microbiota causes chronic inflammation and the progressive accumulation of organ damage in genetically susceptible individuals. In the elderly, IBD is often characterized by a different disease behavior when compared with pediatric and young adult disease. Besides disease behavior, another aspect of the multifaceted impact of age on elderly IBD course is increased susceptibility to infections. In this context, age-of-onset-dependent IBD behavior and clinical course are two major contributors to immune system senescence and change of gut microbiota in older subjects. Here, we review the available literature linking immunosenescence and age-dependent changes in the gut microbiota composition to IBD pathogenesis speculating on their possible implications in disease expression in this age class.

The presence of myenteric plexitis in the proximal resection margins is a predictive factor of early postoperative recurrence in Crohn's disease. To decipher the mechanisms leading to their formation, T-cell interactions with enteric neural cells were studied in vitro and in vivo.

T cells close to myenteric neural cells were retrospectively quantified in ileocolonic resections from 9 control subjects with cancer and 20 patients with Crohn's disease. The mechanisms involved in T-cell adhesion were then investigated in co-cultures of T lymphocytes with enteric glial cells (glia). Finally, the implication of adhesion molecules in the development of plexitis and colitis was studied in vitro but also in vivo in Winnie mice.

The mean number of T cells close to glia, but not neurons, was significantly higher in the myenteric ganglia of relapsing patients with Crohn's disease (2.42 ± 0.5) as compared with controls (0.36 ± 0.08, P = .0007). Co-culture experiments showed that exposure to proinflammatory cytokines enhanced T-cell adhesion to glia and increased intercellular adhesion molecule-1 (ICAM-1) expression in glia. We next demonstrated that T-cell adhesion to glia was inhibited by an anti-ICAM-1 antibody. Finally, using the Winnie mouse model of colitis, we showed that the blockage of ICAM-1/lymphocyte function-associated antigen-1 (LFA-1) with lifitegrast reduced colitis severity and decreased T-cell infiltration in the myenteric plexus.

Our present work argues for a role of glia-T-cell interaction in the development of myenteric plexitis through the adhesion molecules ICAM-1/LFA-1 and suggests that deciphering the functional consequences of glia-T-cell interaction is important to understand the mechanisms implicated in the development and recurrence of Crohn's disease.

Crohn's disease (CD) is regarded as a lifelong progressive disease affecting all segments of the intestinal tract and multiple organs. Based on genome-wide association studies (GWAS) and gene expression data, transcriptome-wide association studies (TWAS) can help identify susceptibility genes associated with pathogenesis and disease behavior. In this review, we overview seven reported TWASs of CD, summarize their study designs, and discuss the key methods and steps used in TWAS, which affect the prioritization of susceptibility genes. This article summarized the screening of tissue-specific susceptibility genes for CD, and discussed the reported potential pathological mechanisms of overlapping susceptibility genes related to CD in a certain tissue type. We observed that ileal lipid-related metabolism and colonic extracellular vesicles may be involved in the pathogenesis of CD by performing GO pathway enrichment analysis for susceptibility genes. We further pointed the low reproducibility of TWAS associated with CD and discussed the reasons for these issues, strategies for solving them. In the future, more TWAS are needed to be designed into large-scale, unified cohorts, unified analysis pipelines, and fully classified databases of expression trait loci.

Patients with inflammatory bowel diseases (IBD) require proactive monitoring both during the active phase to evaluate therapeutic response and during the remission phase to evaluate relapse or colorectal cancer surveillance. However, monitoring may vary between patients with ulcerative colitis (UC) and Crohn's disease (CD), with distinct tools and intervals.

This narrative review aims to focus on modern approaches to IBD monitoring, considering international guidelines and expert consensus.

The most recent European diagnostic guidelines advocate a combination of clinical, laboratory, endoscopic, and radiological parameters to evaluate the disease course of patients with IBD. Unfortunately, the conventional symptom-based therapeutic approach does not improve long-term outcomes and there is no single ideal biomarker available. Endoscopy plays a key role in evaluating response to therapy as well as monitoring disease activity. Recently, bedside intestinal ultrasound (IUS) has gained increasing interest and diffusion as it appears to offer several advantages including the monitoring of therapeutic response.

In light of growing clinical advances, we present a schematic evidence-based monitoring algorithm that can be easily applied in clinical practice which combines all major monitoring modalities, including noninvasive tools such as IUS and video-capsule endoscopy.

Confocal endomicroscopy is a technique allowing the in vivo assessment of the superficial layers of the mucosa. Preliminary studies have already suggested its added value in the assessment of endoscopic remission in inflammatory bowel disease. However, most of these studies were performed on patients still having incomplete mucosal healing. Our aim was to disclose persisting endomicroscopic anomalies in patients with full endoscopic remission and to compare them between vedolizumab- and anti-tumor necrosis factor-treated patients.

We screened patients with Crohn's disease (CD) or ulcerative colitis (UC) treated for more than 6 months with biologic therapy, and being in steroid-free clinical and biological remission. White light endoscopy and probe-based confocal laser endomicroscopy (pCLE) analysis were performed in the ileum, right colon, transverse colon, left colon, and rectum. Full endoscopic remission was defined by a Mayo endoscopic score of 0 in UC and no remaining ulcer or erosion in CD. Patients were prospectively followed up and clinical relapses were recorded.

Seventy-two CD and UC patients treated by biologic therapy and in clinical and biological remission were screened. A total of 37 were also in full endoscopic remission and were included in our study; 183 intestinal segments were analyzed. We found residual pCLE anomalies in most of the patients. These anomalies were not significantly associated with any demographic or clinical characteristic including the treatment received, nor were they associated with histological parameters, levels of C-reactive protein or fecal calprotectin. Among the 37 patients, 7 (18.9%) relapsed over a median follow-up of 33.7 months. The risk of relapse was not associated with any clinical, biological, histologic, or pCLE feature at baseline.

Despite endoscopic, biological, and even histological remission, we found a high prevalence of endomicroscopic abnormalities, which were not different between anti-tumor necrosis factor- and vedolizumab-treated patients. The clinical significance of these anomalies remains to be clarified.

The present study was aimed at identifying a new magnetic resonance enterography (MRE) parameter assessing the clinical outcome of biological therapy in patients with active ileal/ileocolonic Crohn's disease (CD).

Transmural healing (TH) has been associated with improved outcomes in CD. However, some patients with clinical remission and inactive disease at endoscopy do not achieve TH.

Ileal/ileocolonic CD patients scheduled for biological therapy were prospectively evaluated, at baseline (T0) and after 1 year of treatment (T1), with Harvey Bradshaw Index score, blood tests, ileocolonscopy, and MRE. Clinical activity was assessed after 2 years of treatment (T2). Wall thickness ratio (WTR) was calculated in the same affected ileal segment, as the ratio between the ileum wall thickness value at T1 and the ileum wall thickness value at T0.

A total of 103 patients were included. Mean WTR at T1 in nonresponders was significantly higher than in responders. At receiver operating characteristic analysis, WTR values were significantly associated to biological therapy responsiveness. A WTR cutoff value of 0.77 mm was identified to discriminate responders from nonresponders (sensitivity: 79%; specificity: 67%). In responders, the proportion of patients with a WTR<0.77 was significantly higher than the proportion of patients achieving TH at T1. Among patients achieving endoscopic remission, 11/29 (37.9%) presented TH, while 20/29 (68.9%) presented WTR<0.77 ( P : 0.035). At multivariate logistic regression analysis, WTR<0.77 was significantly associated to biological therapy response.

WTR index represents an easy-to-calculate MRE parameter and seems to be a promising tool for monitoring therapeutic response in CD patients during biological therapy.

Surgical resection in Crohn's disease is sometimes the only alternative treating disease complications or refractory disease. The implications of early resection on disease course are still debatable. We aimed to assess the influence of preoperative disease duration on long-term postoperative disease course.

A retrospective analysis of all Crohn's disease patients who underwent an elective primary ileocolic resection between 2010 and 2021 in a single tertiary medical center. The cohort was divided based on disease duration, Group A (47 patients) had a disease duration shorter than 3 years (median of 1 year) and Group B (139 patients) had a disease duration longer than 3 years (median of 11 years).

Surgeries were less complex among Group A as noted by higher rates of laparoscopic assisted procedures (68.1% vs. 45.3%, P = 0.006), shorter surgery duration (134 vs. 167 min, P < 0.0001) less estimated blood loss (72.5 vs. 333 mL, P = 0.016) and faster return of bowel function (3 vs. 4 days, P = 0.011). However, propensity score matching nullified all the differences. Younger age (OR = 0.86, P = 0.004), pre-op steroids (OR = 3.69, P = 0.037) and longer disease duration (OR = 1.18, P = 0.012) were found to be independently significantly associated with severe complications. After a median follow-up time of 71.38 months no significant differences were found between the groups in terms of endoscopic (P = 0.59), or surgical recurrences rates (P = 0.82).

The main effect of preoperative short disease duration was noted within the surgical complexity; however, matching suggests confounders as cause of the difference. No significant long-term implication was noted on disease recurrence.

In the ideal world prognostication or predicting disease course in any chronic condition would allow the clinician to anticipate disease behaviour, providing crucial information for the patient and data regarding best use of resources. Prognostication also allows an understanding of likely response to treatment and the risk of adverse effects of a treatment leading to withdrawal in any individual patient. Therefore, the ability to predict outcomes from the onset of disease is the key step to developing precision personalised medicine, which is the design of medical care to optimise efficiency or therapeutic benefit based on careful profiling of patients. An important corollary is to prevent unnecessary healthcare costs. This paper outlines currently available predictors of disease outcome in IBD and looks to the future which will involve the use of artificial intelligence to interrogate big data derived from various important 'omes' to tease out a more holistic approach to IBD.

Although the importance of mucosal healing has been suggested in Crohn's disease, it is difficult to repeat endoscopy, especially for the entire small bowel. Recently, serum leucine-rich alpha-2 glycoprotein (LRG) has been used as a surrogate marker of endoscopy. However, few studies have investigated a correlation between LRG and mucosal injury of the entire small bowel.

We retrospectively analyzed the clinical data of 30 patients with Crohn's disease from June 2020 to August 2022 at Yamaguchi Red Cross Hospital. All the patients were surveyed through the gastrointestinal tract by esophagogastroduodenoscopy, total colonoscopy, and capsule endoscopy (CE). Subjects with mucosal injury only in the small bowel were selected. Then, we assessed the relationship between serum biomarkers (LRG, C-reactive protein [CRP], hemoglobin, albumin) and small bowel mucosal injury scores (Lewis score [LS], Capsule Endoscopy Crohn's Disease Activity Index [CECDAI], and Crohn's Disease Activity in Capsule Endoscopy [CDACE]) calculated by CE.

LRG and CRP were significantly correlated with small bowel mucosal injury scores (LS, CECDAI, CDACE) (p < 0.05, Spearman's rank correlation coefficient). The degree of correlation was greater for LRG than for CRP.

LRG is a useful surrogate marker that closely reflects small bowel mucosal injury in the entire small bowel.