Ulcerative Colitis Research Articles

Lifestyle restrictions are associated with impaired quality of life but not reduction in relapse in ulcerative colitis.

Patients with ulcerative colitis (UC) in remission commonly restrict thir lifestyle to prevent relapse; however, the effectiveness and impact on quality of life (QOL) is unclear. This study investigated whether lifestyle restrictions are associated with relapse reduction and assessed their impact on QOL. This multicenter, prospective cohort study was conducted in Japan (2018-2021) via the YOURS registry, enrolling patients with UC in clinical remission. Patients were followed for 2 years. A baseline questionnaire evaluated lifestyle restrictions in diet, work/study/housework, and physical exercise. QOL was assessed by Disease Impact Scale every 3 months during the first year of follow-up. Associations of lifestyle restrictions with relapse and QOL were assessed by Cox regression analysis and linear mixed-effects models, respectively. Among 911 patients in clinical remission for > 90 days, 63% had adopted dietary avoidance; 47%, work/study/housework avoidance; and 8%, physical exercise avoidance. Overall, 216 patients relapsed. Lifestyle restrictions were not associated with reduced risk of relapse (multivariableadjusted hazard ratios [95% confidence interval]: dietary avoidance, 1.08 [0.81-1.44]; and work/study/housework avoidance, 1.14 [0.87-1.50]); physical exercise avoidance was associated with increased relapse (multivariable-adjusted hazard ratio, 1.58; 95% confidence interval, 1.02-2.44). All lifestyle restrictions were associated with impaired QOL (P <0.01). Lifestyle restrictions were not associated with relapse reduction in patients with UC; however, they were associated with impaired QOL. Clinicians should engage in evidence-based discussions with patients with UC in remission regarding lifestyle restrictions (UMIN Clinical Trials Registry; UMIN000031995).

Effect of Aegle marmelos Extract-Phospholipid Complexes in Dextran Sulfate Sodium-Induced Ulcerative Colitis in Rats.

Ayurvedic texts mention the use of Aegle marmelos fruit in colitis and other gastrointestinal ailments. The polyphenolic contents of the fruit, however, have poor bioavailability, limiting their therapeutic use. The study aimed to develop and optimise the A. marmelos fruit extract-phospholipid (AMEP) complex to improve the oral bioavailability of the A. marmelos extract (AME), and compare the in vivo effect of AME and AMEP in dextran sulfate sodium (DSS)-induced ulcerative colitis in rats. The research work is the first of its kind to use a hydroalcoholic extract of A. marmelos fruit in the preparation of phospholipid complexes for ameliorating UC. The complexes were prepared using the solvent evaporation method and optimised by Box-Behnken design. The work compares the in vivo activity of plain AME, its phospholipid complexes, and the standard drug (mesalamine) in the alleviation of chemical-induced colitis in rats. AMEP was optimised using response surface methodology by Box-Behnken design. AMEP was characterised using scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, zeta analysis, and particle size analysis. A DSS-induced rat model was used in vivo studies to mimic ulcerative colitis. The pathogenesis of the disease was assessed by evaluating the levels of oxidative stress markers [nitric oxide (NO), malondialdehyde (MDA), and superoxide dismutase (SOD) activity], cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)], disease activity index, colon length, and histopathology. The characterization confirmed the formation of AMEP, having a particle size of 673.6±4.30 nm, polydispersity index of 0.224±0.010, and zeta potential of -42.6 mV±0.51. The NO, MDA, TNF-α, and IL-6 levels were significantly reduced (p<0.0001, p<0.005, p<0.0001, p<0.01), and the SOD level was significantly increased (p<0.05) in AMEP-treated groups compared to the AME-treated groups. These findings suggessts that AMEP has a powerful potential to reduce the levels of oxidative markers and inflammatory cytokines, making it a promising treatment for ulcerative colitis.

Atractylenolide-1 Alleviates Ulcerative Colitis via Restraining RhoA/ROCK/MLC Pathway-Mediated Intestinal Barrier Dysfunction.

Using Atractylenolide-1 (AT-1) is a confident strategy for the treatment of ulcerative colitis (UC) due to its natural origin and notable pharmacological activity. The study investigated the therapeutic effect of AT-1 in dextran sodium sulfate (DSS)-induced mice and Caco-2 cells while also exploring the underlying molecular mechanisms. In this study, AT-1 treatment could reduce weight loss and colon shortening and significantly reduce disease activity index (DAI), spleen index, and histopathological scores in UC mice. And AT-1 was observed to restore cell necrosis and monolayer damage and restored F-actin-mediated tight junction (TJ) protein redistribution to alleviate mucosal injury in UC mice and Caco-2 cells. Moreover, AT-1 regulated alanine, aspartic acid, and glutamate metabolism; increased the content of related metabolites; and promoted cell proliferation to restore damaged mucous membranes in UC mice. The results of molecular docking and molecular dynamics simulation showed that the binding of AT-1 to RhoA had a stable conformation, and it was speculated that RhoA was the main target of AT-1. Further investigations revealed that the interference of RhoA disrupted the regulatory pathway of AT-1. Thus, AT-1 could inhibit the reduction of TJ proteins, alter DSS-mediated cytoskeletal migration, promote amino acid metabolism, and subsequently reduce the permeability of the colon epithelium, thereby restoring mucosal barrier dysfunction features.

Effect of moxibustion on P2X7R/NF-κB pathway in ulcerative colitis rats with repeated induction of DSS

Effect of moxibustion on P2X7R/NF-κB pathway in ulcerative colitis rats with repeated induction of DSS

Biological Ageing and the Risk of Inflammatory Bowel Disease: Exploring the Role of Lifestyle and Genetic Susceptibility in a Nationwide Prospective Study.

Accelerated biological aging has been linked to an increased risk of inflammatory bowel disease (IBD), though its interplay with genetic susceptibility remains unclear. We analyzed data from 310 441 UK Biobank participants to investigate associations between PhenoAge acceleration (a measure of biological aging), genetic risk, and the incidence of ulcerative colitis (UC) and Crohn's disease (CD). During follow-up, 3364 participants (1.08%) developed UC and 1831 (0.59%) developed CD. After adjusting for all confounders, each 1-year increase in PhenoAge acceleration was associated with a 6.9% increase in UC risk (HR = 1.069, 95% CI, 1.063-1.074) and an 8.5% increase in CD risk (HR = 1.085, 95% CI, 1.079-1.092). Participants who were biologically older showed a higher risk of UC (HR = 1.928, 95% CI, 1.799-2.067) and CD (HR = 2.557, 95% CI, 2.330-2.807) compared with their younger counterparts. Moreover, PhenoAge acceleration partially mediated the associations of alcohol consumption and cigarette smoking with UC and CD risk (11.2%-27.2%). We observed dose-response associations between polygenic risk scores and both UC and CD. Compared with the bottom quintile, high-risk participants (top quintile) showed a 439.9% increase (HR = 2.229, 95% CI, 1.949-2.550) in UC risk and a 501.7% increase (HR = 6.017, 95% CI, 5.254-6.891) in CD risk. Notably, individuals with both high genetic risk and accelerated aging exhibited the greatest susceptibility (UC: HR = 11.569, 95% CI, 9.658-13.858; CD: HR = 12.018, 95% CI, 9.569-15.094). PhenoAge acceleration may serve as a useful biomarker for identifying high-risk individuals, offering potential for integration into targeted prevention strategies and personalized treatment approaches for IBD.This study explores how accelerated biological aging (PhenoAge acceleration) and genetic susceptibility influence the risk of inflammatory bowel disease. Findings indicate that higher PhenoAge acceleration and genetic risk scores significantly increase the likelihood of developing ulcerative colitis and Crohn's disease.

Decreased Fecal Nicotinamide and Increased Bacterial Nicotinamidase Gene Expression in Ulcerative Colitis Patients.

Ulcerative colitis (UC) is significantly linked with gut microbiota, which is essential for maintaining gut health. Their metabolites mitigate gut inflammation and bolster barrier function. Among these metabolites, we focused on vitamin B3, which has been reported to improve the pathogenesis of UC in mice. This study aimed to compare fecal vitamin B3 and gut microbiota between non-UC and UC patients. We assessed fecal metabolites and gut microbiota in 71 UC patients (UC group) and 72 non-UC patients (non-UC group) matched by sex and age in 10-year intervals. Fecal samples were collected and metabolites were analyzed using capillary electrophoresis time-of-flight mass spectrometry. Bacterial DNA was extracted for 16S rRNA gene sequencing. We analyzed fecal nicotinamide levels and gut microbiota composition, employing statistical adjustments for confounding factors. We found that the UC group exhibited significantly lower fecal nicotinamide levels and α-diversity (Shannon index) compared to the non-UC group. The relative abundance of bacterial genera such as Treponema, UCG-002, and Fusicatenibacter was decreased, while Sellimonas, Fournierella, and Oscillospira were increased in the UC group. Moreover, a negative correlation was observed between Sellimonas abundance and fecal nicotinamide levels in the UC group. Additionally, the UC group showed higher expression of a bacterial gene encoding nicotinamidase compared to the non-UC group. These findings suggest that gut microbiota dysbiosis contributes to reduced vitamin B3 metabolism in UC patients. The study highlights the potential of replenishing vitamin B3 metabolic pathways as a novel therapeutic approach for UC treatment.

Six-Year Observation Data Reveal Reduction in Concomitant Steroid Overuse for Inflammatory Bowel Disease in Germany.

Maintenance and/or prolonged treatment with oral corticosteroid (OCS) in inflammatory bowel disease (IBD) is not recommended, yet remains common. This study assessed concomitant OCS use and overuse in IBD patients in Germany from 2017 to 2022. We retrospectively analyzed German claims data (2017-2022). Patients over 18 years of age with continuous insurance and at least s2 quarterly diagnoses of Crohn's disease (CD) or ulcerative colitis (UC) within 2 years were included. To increase the diagnostic certainty and clinical relevance, only patients with IBD who were currently receiving any form of IBD therapy were included in the analysis. OCS overuse was defined as receiving ≥2 OCS prescriptions within 1 year alongside other IBD medications. The study identified 9407 patients with confirmed CD and 11 772 patients with confirmed UC who were treated with IBD medications excluding OCS monotherapy within the observation period. Among those, 42.8% of CD patients and 39.0% of UC patients were treated with concomitant OCS (CD vs. UC, P < .0001), while 31.3% of CD patients and 29.4% of UC patients exhibited concomitant OCS overuse (CD vs. UC, P < .01). Concomitant OCS use and overuse were more common among younger age groups (P < .01). OCS use and OCS overuse decreased significantly (P < .0001) from 2017 to 2022. This study provides real-world insights into the patterns of OCS use and overuse in IBD patients. The continued reliance on OCS is highlighted, particularly in CD patients and younger age groups. Notably, steroid overuse has decreased significantly over the last 6 years.

Deucravacitinib in Patients With Inflammatory Bowel Disease: 12-Week Efficacy and Safety Results From Three Randomized Phase 2 Studies in Crohn's Disease and Ulcerative Colitis.

Tyrosine kinase 2 is a downstream intracellular mediator of interleukin-23 signaling, which has a key role in the pathogenesis of inflammatory bowel disease. Deucravacitinib is a novel, oral, selective, allosteric tyrosine kinase 2 inhibitor currently approved for the treatment of adults with moderate to severe plaque psoriasis. Here we describe three randomized, double-blind, placebo-controlled phase 2 studies of deucravacitinib in patients with moderately to severely active Crohn's disease (LATTICE-CD [NCT03599622]) or ulcerative colitis (LATTICE-UC [NCT03934216] and IM011-127 [NCT04613518]). Patients were randomized to receive placebo or twice-daily deucravacitinib 3mg or 6mg (LATTICE-CD), 6mg (LATTICE-UC), or 12mg (IM011-127) for 12 weeks. Coprimary endpoints for LATTICE-CD were clinical remission and endoscopic response at Week 12. The primary endpoint was clinical remission (per modified Mayo score) at Week 12 for LATTICE-UC and clinical response (per modified Mayo score) at Week 12 for IM011-127. A total of 239 (LATTICE-CD), 131 (LATTICE-UC), and 38 (IM011-127) patients were randomized. The primary endpoints were not met for all three studies, which resulted in early study termination for LATTICE-CD and IM011-127. High efficacy rates were observed in placebo groups throughout the studies. In all studies, the safety profile of deucravacitinib was consistent with the known safety profile observed in patients with psoriasis, and no new safety signals were observed. Deucravacitinib at multiple doses did not demonstrate significant clinical benefit vs placebo in moderately to severely active Crohn's disease or ulcerative colitis. Deucravacitinib was safe and well-tolerated.

Targeting SLC7 A11 Ameliorates Ulcerative Colitis by Promoting Efferocytosis Through the ERK1/2 Pathway.

This study investigates the effect and underlying mechanism of targeting SLC7A11 in mitigating dextran sulfate sodium (DSS)-induced intestinal inflammation and injury in colitis. We utilized wild-type and SLC7A11-/+ mice to assess the inflammatory damage in DSS-induced colitis in vivo. In vitro, colon tissues from patients with ulcerative colitis were analyzed to compare SLC7A11 expression between inflamed and non-inflamed regions. Further mechanistic insights were obtained using Caco-2 cells and bone marrow-derived dendritic cells (BMDCs). In human colon tissues, SLC7A11 expression was significantly elevated in inflamed regions compared to non-inflamed areas, particularly in dendritic cells. In vivo inhibition of SLC7A11 markedly alleviated DSS-induced colitis symptoms. In vitro, suppressing SLC7A11 restored the integrity of the Caco-2 monolayer intestinal epithelial model. Both knockout and inhibition of SLC7A11 enhanced ERK1/2 phosphorylation and increased efferocytosis in BMDCs. Targeting SLC7A11 augments dendritic cell efferocytosis and preserves intestinal epithelial barrier function, potentially offering a therapeutic avenue for alleviating ulcerative colitis.

Risk of colectomy is decreasing among newly diagnosed Finnish ulcerative colitis patients.

The risk of colectomy in patients with ulcerative colitis (UC) has decreased since the 20th century. Our aim was to determine the colectomy risk of newly diagnosed Finnish UC patients and compare the risk of prebiological and biological era. We used the registry of the Social Insurance Institution of Finland to find newly diagnosed UC patients and colectomies were collected from the Finnish Institute for Health and Welfare. The patients were stratified according to the year of UC diagnosis into three groups: 2000-05 (prebiological), 2006-12 and 2013-20. We identified 32,108 UC patients and 2,195 colectomies performed on them. The 1-, 5- and 10-year cumulative colectomy risk was 1.0%, 4.7% and 7.3% respectively. The risks declined with the incidence rate ratio (IRR) 0.98 (95% confidence interval (CI) 0.96-0.99), IRR 0.97 (CI 0.96-0.98) and IRR 0.97 (CI 0.96-0.99), respectively. Men and the paediatric group had higher risk of surgery (IRR 1.25, CI 1.15-1.37 and IRR 1.69, CI 1.51-1.89). Colectomy risks were lower in the last study era (IRR 0.757, CI 0.574-0.997 in 1-year and IRR 0.70, CI 0.61-0.82 in 5-year risk), and the 10-year risk was also decreased in the second era (IRR 0.87, CI 0.78-0.97) compared to the prebiological era. The paediatric population had lower risk of surgery only in the last era, whereas the risk among the elderly remained constant. The risk of colectomy in UC patients has decreased in the 21st century.

Identifying Lactylation-related biomarkers and therapeutic drugs in ulcerative colitis: insights from machine learning and molecular docking

BackgroundUlcerative colitis (UC), a chronic relapsing-remitting inflammatory bowel disease. Recent studies have shown that lactylation modifications may be involved in metabolic-immune interactions in intestinal inflammation through epigenetic regulation, but their specific mechanisms in UC still require in-depth validation.MethodsWe conducted comparative analyses of transcriptomic profiles, immune landscapes, and functional pathways between UC and normal cohorts. Lactylation-related differentially expressed genes were subjected to enrichment analysis to delineate their mechanistic roles in UC. Through machine learning algorithms, the diagnostic model was established. Further elucidating the mechanisms and regulatory network of the model gene in UC were GSVA, immunological correlation analysis, transcription factor prediction, immunofluorescence, and single-cell analysis. Lastly, the CMap database and molecular docking technology were used to investigate possible treatment drugs for UC.ResultsTwenty-two lactylation-related differentially expressed genes were identified, predominantly enriched in actin cytoskeleton organization and JAK-STAT signaling. By utilizing machine learning methods, 3 model genes (S100A11, IFI16, and HSDL2) were identified. ROC curves from the train and test cohorts illustrate the superior diagnostic value of our model. Further comprehensive bioinformatics analyses revealed that these three core genes may be involved in the development of UC by regulating the metabolic and immune microenvironment. Finally, regorafenib and R-428 were considered as possible agents for the treatment of UC.ConclusionThis study offers a novel strategy to early UC diagnosis and treatment by thoroughly characterizing lactylation modifications in UC.

Developing IBD Outcome Effect Size Thresholds to Inform Research, Guidelines, and Clinical Decisions.

When designing clinical trials, interpreting trial outcomes for guideline development or sharing decisions with patients in clinical practice, the clinical outcomes used and the implicit choices on what constitutes a clinically significant finding can vary greatly. This can lead to diversity or even inequity in care offered to patients with inflammatory bowel disease (IBD). The GRADE approach to guideline development has proposed a process to address this prospectively to solve these issues, but this has never been used in IBD. We aimed to develop the first international consensus set of outcome thresholds to establish their use in Crohn's disease and ulcerative colitis. A Delphi methodology was used to develop a consensus. An online survey was conducted by inviting stakeholders from the British Society of Gastroenterology through a 2-phase process. Participants were asked to select important clinically relevant outcomes and were asked about what magnitude of the effect that they consider large, moderate, small, or trivial for each clinical trial outcome in line with the GRADE guidance. The results were fed back to all participants to ensure consensus agreement. Then, further surveys were sent to Europe and North America to ensure validity and international triangulation of the dataset. Data are presented as mean ± SD. A total of 131 clinical stakeholders participated, including clinicians, IBD nurses, and a small number of patients with IBD. Clinical remission and serious adverse events were considered the most critical outcomes for Crohn's disease, while clinical remission and endoscopic remission were considered the most critical outcomes for ulcerative colitis. The consensus results for thresholds of small, moderate, and large outcome effect sizes were agreed on as follows: clinical remission, 11 ± 6%, 20 ± 8%, and 31 ± 13%; endoscopic remission, 9 ± 5%, 17 ± 9%, and 28 ± 14%; and serious adverse events 6 ± 6%, 11 ± 9%, and 17 ± 12%, respectively. No significant differences were observed for responses for each condition. This is the first study to develop a consensus on magnitude thresholds for outcomes in IBD. These thresholds have been used in the development of the 2024 British Society of Gastroenterology guidelines for the management of IBD but can and should also be used by study designers and, most importantly, by clinicians when discussing evidence with patients as part of shared decision making. Future work to validate these findings globally and with other groups, including patients, is needed.

Therapeutic Potential and Translational Challenges for Bacterial Extracellular Vesicles in Inflammatory Bowel Disease.

Despite the availability of numerous new immune-directed therapeutics, the major constituents of inflammatory bowel disease (IBD)-ulcerative colitis (UC) and Crohn's disease (CD)-continue to afflict millions worldwide, resulting in significant morbidity and long-term health risks. IBD results from a triad of immune, environmental (eg, gut microbiome), and genetic (including epigenetic) mechanisms, and therefore has been subject to a wide variety of therapeutic strategies. Among these, the administration of probiotics, particularly Gram-positive lactic acid bacteria (LAB), targeting both immune and environmental factors, has shown promising potential for efficacy in selected populations in early clinical trials. However, knowledge gaps and inconsistent efficacy currently prevent recommendations for the use of probiotics in larger IBD patient populations. The inconsistent efficacy of probiotics is likely due to variable cell viability and potency after administration, further exacerbated by IBD patient heterogeneity. Thus, an alternative to live probiotics for IBD has emerged in the form of bacterial extracellular vesicles (BEVs)-cell-secreted nanovesicles containing abundant bioactive cargo that, like live probiotics, can regulate immune and environmental factors but with fewer viability limitations and safety concerns. In this review, we summarize the work done to date establishing the potential of BEVs to provide the therapeutic benefits in IBD and discuss the hurdles BEVs must overcome to achieve clinical translation. We also consider future directions for BEV therapeutics, especially treatment potential for necrotizing enterocolitis (NEC), which shares similarities in pathophysiology with IBD.

Cytomegalovirus infection in patients with active ulcerative colitis: a prospective observational study.

The role of cytomegalovirus (CMV) infection in the course of inflammatory bowel disease is still controversial. We aimed to prospectively evaluate the course of ulcerative colitis in patients with exacerbation, in whom CMV status was examined using immunohistochemistry of bowel biopsies. In a single centre, we followed-up consecutive patients admitted for moderate or severe ulcerative colitis flare between 2016 and 2019. Colectomies, repeated hospitalisations, major treatment modifications, and quality of life (QoL) were recorded. The relationship between categorical variables was examined with the χ2 statistical test or Fisher's exact test. Of 84 patients, 16 (19%) were CMV-positive. A Mayo endoscopic score of 3 was more frequent in CMV-positive than CMV-negative patients (81.2 vs. 51.5%; P = 0.048) as was corticosteroid treatment (81.2 vs. 54.4%; P = 0.015). Median follow-up was 2.1 years (range: 0.3-3.6 years). Colectomy was performed in 20 (23.8%) patients, with similar rates in CMV-positive (25%) and CMV-negative patients (23.5%; P = 1.0). Similarly, no differences were found in the frequency of hospitalisation and QoL. The percentage of patients who started biological treatment was higher in the CMV-negative than in the CMV-positive group (58.8 vs. 18.8%; P = 0.005). CMV infection was present in 19% of consecutive patients hospitalised for ulcerative colitis flare. Corticosteroid treatment and severe endoscopic lesions were observed more often in patients with CMV-positive. In the following 2.1 years, the colectomy rate did not differ between patients with CMV-positive and CMV-negative. Routine screening for CMV in ulcerative colitis exacerbation is not advisable.

Surgical trend including minimally invasive surgeries for ulcerative colitis in the COSUC study: the largest multicenter cohort study in Japan.

The number of patients with ulcerative colitis (UC) is increasing rapidly in Asia. No large study has evaluated the clinical outcomes of hand-sewn ileal pouch-anal anastomosis (IPAA). This study aimed to create a large database of the surgical outcomes of UC, present the trends of surgical procedures, and evaluate the impact of minimally invasive procedures on UC. Data of patients first treated from 2005 to 2019 were collected; two-staged surgery data were extracted, and minimally invasive surgery (MIS) and open surgery (OS) outcomes were compared using propensity-score matching. The data of 1558 cases were selected as the main analysis set. The number of surgical cases of UC has been increasing, with increasing proportion of MIS cases (2005: 43%, 2019: 84%). The median age of the patients increased in these 15years (39.5-56years old). Of 873 patients who underwent two-staged surgery, after 3:1 matching, 408 MIS and 176 OS cases were compared. Hand-sewn anastomoses were performed in 293 MIS (72.0%) and 142 OS-IPAA (80.7%) cases. The proportion of early complications (≥ Grade 3) did not vary between the two groups. Intraoperative blood loss was lower and blood transfusions were less frequent in the MIS group. The proportion of MIS for UC has rapidly increased over the past 15years. The total number of MIS and OS complications did not vary significantly between the groups. The short-term advantages of MIS include reduced blood loss and less necessity for blood transfusions.

Janus Kinase Inhibitors in the Treatment of Crohn’s Disease and Ulcerative Colitis: A Review

Introduction and purpose: Insufficient efficacy and adverse effects of classical therapies for inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn's disease, have prompted the search for new, more targeted treatment methods. Janus kinase (JAK) inhibitors are a new group of oral drugs that modulate the proinflammatory cytokine signaling pathway. The aim of this review is to present the state of knowledge on the efficacy and safety of currently registered JAK inhibitors in the treatment of IBD. Review Methods: A systematic search of the PubMed database was conducted, focusing on publications from the last five years as well as selected key earlier studies. The search strategy included relevant keywords related to Janus kinase (JAK) inhibitors and inflammatory bowel disease (IBD). The most pertinent articles aligned with the study objective were reviewed and included. State of knowledge: JAK inhibitors, such as tofacitinib, upadacitinib, and filgotinib, have shown high efficacy in the treatment of moderate to severe UC and CD, especially in patients with insufficient biological therapy response. Clinical studies confirm their efficacy in inducing and maintaining remission and improving endoscopic findings. The most common adverse events are infections (including herpes zoster), and elevation of creatine kinase and lipids. The safety profile remains acceptable, although it requires monitoring, especially at higher doses, and further investigation. Summary: JAK inhibitors are an effective and promising therapeutic option for IBD, offering a rapid onset of action and good symptom control. Despite the favorable clinical effects, an individual approach to treatment and monitoring for adverse effects are necessary, especially with long-term use.

Second-line strategies after anti-TNF failure in chronically active, moderate-to-severe ulcerative colitis: a retrospective, multicentre cohort study

ABSTRACT Background Many ulcerative colitis (UC) patients require the use of second-line agents after the failure of anti-TNF therapy. Research design and methods We conducted a multicenter, retrospective study including 683 chronically active, moderate-to-severe UC patients who failed first-line anti-TNFs. The rate of treatment persistence and colectomy-free survival was assessed up to 3 years after the initiation of second-line therapy. Predictors for colectomy and persistence were investigated. Results After the failure of the first-line anti-TNF, ustekinumab had superior persistence and colectomy-free survival rates compared to tofacitinib (p = 0.05; p = 0.001) and vedolizumab (p = 0.02; p = 0.05), but significant difference was only found in persistence rates in comparison with anti-TNFs (p < 0.001). Regardless of the number of prior anti-TNFs, significantly higher persistence (p = 0.05) and colectomy-free survival rates (p = 0.01) were observed over 2 years with ustekinumab than with vedolizumab or tofacitinib, whereas ustekinumab’s superiority over tofacitinib seemed to disappear by the third year. Hypoalbuminaemia (p = 0.002) and shorter disease duration at second-line initiation (p = 0.03) increased, while concomitant immunomodulators (p = 0.05) reduced the risk for colectomy. Shorter disease duration (p = 0.01) and primary non-response to the previously used anti-TNF (p < 0.001) negatively influenced persistence with second-line non-TNF-targeted agents. Conclusion After first-line anti-TNF failure, switching to a non-anti-TNF agent is worth considering in moderate-to-severe UC.

Influence of Familial Inflammatory Bowel Disease History on the Use of Immunosuppressants, Biological Agents and Surgery in Patients with Pediatric-Onset of the Disease in the Era of Biological Therapies. Results from the ENEIDA Registry

Background: Pediatric-onset familial inflammatory bowel disease (IBD) may differ from sporadic pediatric-onset IBD in its genetic and environmental background and may have distinct clinical and therapeutic implications. Objective: To evaluate the influence of a positive family history of IBD on the use of medical therapies and surgical interventions in adult patients with pediatric-onset IBD. Methods: Retrospective case–control study using the Spanish ENEIDA registry, including adults diagnosed with pediatric-onset IBD since 2006. Familial forms (FFs) (defined by a first-degree relative with IBD) and sporadic forms (SF) (with no relatives of any grade with IBD) were matched 1:4 by type of IBD, sex, age at IBD diagnosis, disease location, disease pattern, development of perianal disease and smoking status at diagnosis. The study outcomes were the use of immunomodulators, biological therapies, intestinal surgery, and perianal surgery during follow-up. Results: Six-hundred and fifty-five Crohn’s disease (CD) (131 FF) and 440 ulcerative colitis (UC) (88 FF) patients were included. Immunomodulators, biological therapy, and intestinal surgery were used evenly among FF and SF patients for both UC and CD. However, a higher requirement for perianal surgery among FF-CD patients (18.3% vs. 10.5%, p = 0.014), together with a shorter time to perianal surgery (11 vs. 20 months, log-rank p = 0.004), was observed. Conclusions: Patients with FF of pediatric-onset IBD do not exhibit an increased use of immunomodulators, biological agents, or intestinal surgery, but do exhibit a higher need for perianal surgery, as compared to patients with SF pediatric-onset IBD.

Efficacy and safety of dual-targeted therapy for refractory inflammatory bowel disease: a retrospective case series from three tertiary general hospitals in China

AimDual-targeted therapy (DTT) may offer a promising approach for treating refractory inflammatory bowel disease (IBD). The aim of this case series was to evaluate the safety and clinical response of DTT in clinical practice.MethodsWe retrospectively analyzed data from refractory inflammatory bowel disease (IBD) patients receiving dual-target therapy (DTT) across several Chinese IBD centers. The treatment combinations included biologic agents (infliximab (IFX), adalimumab (ADA), vedolizumab (VDZ), and ustekinumab (UST) and oral small molecule tofacitinib (TOF). We collected baseline characteristics, clinical and endoscopic activity indices, inflammatory markers (C-reactive protein and albumin), and adverse events to evaluate the clinical effectiveness, endoscopic response, biochemical remission, and safety profile of DTT.ResultsA total of 8 patients with ulcerative colitis (UC) and 10 with Crohn’s disease (CD) underwent DTT at three tertiary hospitals in China. All corticosteroids initiated at baseline (six cases) were completely discontinued within 3 months. Clinical response rates were 88.23% (15/17), 91.67% (11/12), and 100% (7/7) at 3, 6, and 9 months, respectively. Endoscopic response was achieved in 88.89% (8/9) of patients who were evaluated at 9 months. Adverse events included ustekinumab-associated arthralgia and alopecia in one UC patient and tofacitinib-related allergic purpura in another, both of which were subsequently transitioned to monotherapy. Two CD patients developed infections (Clostridium difficile and bacterial intestinal infection) at 3 months, were treated with oral antibiotics, and successfully continued their original DTT regimens.ConclusionOur findings suggest that dual-target therapy demonstrates promising efficacy and an acceptable safety profile in refractory IBD patients. DTT may represent a valuable therapeutic option for patients who have not responded to conventional monotherapies.

Prevalence and clinical characteristics of children with coexisting coeliac disease and inflammatory bowel disease.

Growing evidence suggests that coeliac disease (CeD) is more common in patients with inflammatory bowel disease (IBD) but diagnostic confusion remains due to overlapping histological and clinical features. Few studies have investigated this relationship in children. We aimed to assess the prevalence of CeD in our paediatric IBD cohort and define the characteristics of IBD when CeD coexists. We conducted a retrospective study of all patients <18 years old diagnosed with IBD in Southampton Children's Hospital between January 2019 and December 2023. Patients were identified using our IBD database, and data were collected on diagnosis, endoscopy, histopathology, serology, IBD treatment and surgery using electronic patient records. 18 of the 479 children with IBD were also diagnosed with CeD (3.75%). 14 underwent duodenal biopsy on gluten, with 13 fulfilling Marsh classification 2-3. Eight children had Crohn's disease, five had ulcerative colitis and five had IBD-unclassified. 16 out of 18 demonstrated colonic disease; 11 out of 18 had pancolitis. There was no significant difference in the rate of biological therapy use between the IBD-CeD and non-coeliac groups (50% vs 68%). No patients with IBD-CeD underwent IBD surgery. 1 in 25 children with IBD had coexisting CeD. Pancolitis was the most prominent IBD phenotype but a diagnosis of CeD was not associated with increased escalation to biological therapy, and no patients required surgery. These findings help to describe the paediatric IBD-coeliac phenotype and demonstrate the importance of considering IBD in children with refractory CeD and screening for CeD in children presenting with IBD.