Journal of Crohn's & colitis最新文献

Background: Achieving endoscopic remission is a key therapeutic goal in inflammatory bowel disease (IBD) that is associated with improved disease outcome. Transmural and intestinal barrier healing represent emerging targets, as they have similarly been associated with favourable disease behaviour. To date, no study has compared these novel end-points and their impact on avoiding deleterious disease outcome.

Methods: Clinically remittent IBD patients underwent ileocolonoscopy with assessment of intestinal barrier function by endomicroscopy. Transmural healing was assessed by magnetic resonance imaging or intestinal ultrasonography. Endoscopic and histologic disease activity were prospectively assessed along established scores. During subsequent follow-up (FU), patients were closely monitored for disease activity and major adverse outcomes (MAO): Disease flares, IBD-related hospitalization/surgery, initiation or escalation of systemic steroid, immunosuppressive or targeted advanced therapy.

Results: Eighty patients (47 Crohn's disease [CD], 33 ulcerative colitis [UC]) were included. During a mean FU of 34 (CD) and 18 (UC) months, 72% of CD and 85% of UC patients experienced MAO. Intestinal barrier healing exhibited the highest accuracy for predicting MAO-free survival in UC and CD patients and outcompeted transmural healing for predicting the further disease course. Both barrier healing and transmural healing showed higher diagnostic accuracy in forecasting the future course of disease when compared to endoscopic and histologic remission.

Conclusion: Intestinal barrier healing is superior to transmural healing to prevent disease progression in clinical remittent IBD patients while both barrier and transmural healing showed superiority over endoscopic and histologic remission. Hence, barrier and transmural healing are emerging end-points potentially refining disease monitoring and outcome prediction.

Demyelinating diseases, particularly multiple sclerosis (MS), present a unique therapeutic challenge in the management of inflammatory bowel disease (IBD). Although rare, the co-occurrence of IBD and demyelinating disorders is well-documented and may reflect shared immune, genetic, and environmental risk factors. As the therapeutic landscape of IBD expands to include biologics and small molecules that target immune pathways also implicated in MS, concerns around neurological safety have grown. In particular, anti-tumor necrosis factor agents have been consistently linked to new-onset or worsening demyelinating events, while other treatments such as sphingosine-1-phosphate receptor modulators and natali-zumab are licensed for both IBD and MS, though real-world data in patients with coexisting disease remain limited. This review synthesizes current evidence regarding the neurological safety and efficacy of IBD therapies in the context of demyelinating disease. It proposes a practical framework for clinicians, addressing management strategies for patients with confirmed MS, those at increased risk, and individuals who develop neurological symptoms during treatment. In the absence of formal guidelines, multidisciplinary collaboration, early recognition of symptoms, and careful treatment selection are important to optimize both gastrointestinal and neurological outcomes.

Background and aims: Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract. While infliximab (IFX) offers significant benefits, 10%-30% of patients remain non-responders initially. This study employs artificial intelligence with multimodal integration to improve treatment response prediction and advance precision medicine.

Methods: We conducted a retrospective analysis of clinical data from patients with CD. The endpoint event was defined as primary non-response within 14 weeks of treatment. The multimodal dataset included laboratory indices, computed tomography enterography (CTE), and endoscopic histopathology based on whole-slide biopsy images. A TabNet model, originally designed for tabular data and here applied to clinical and laboratory features, was developed using a multi-instance learning framework to incorporate this multimodal information for predicting primary non-response to IFX. Finally, the multimodal model was validated in an independent external test cohort.

Results: The study included 188 patients, with 93 in the internal training set, 38 in the internal validation set, and 57 in the test set from an independent external cohort. The model utilizing pathological features achieved an area under the receiver operating characteristic (AUC) of 0.789 in internal validation. When combining pathological and radiological features, the AUC was 0.844. The optimal multimodal model integrating histology, radiology, and clinical features achieved an AUC of 0.852 in the internal validation set and 0.858 in the external test set.

Conclusions: The study developed a multimodal deep learning model accurately predicting IFX primary non-response, offering a tool to guide individualized therapy and improve CD outcomes.

Background and aims: Inflammatory Bowel Disease (IBD) is a gastrointestinal, auto-inflammatory disease with a chronic relapsing and remitting course, whose diagnosis is based on several exams assessing intestinal infiammation and clinical assessment. Furthermore, only 40-60% of patients respond to therapy, making identification of reliable markers of disease or predictors of disease course and therapy response of great interest to the medical community. The existence of extrachromosomal circular DNA (eccDNA) is well established, and has become a promising biomarker for different types of cancer. Here, we investigate eccDNA in patients affected by IBD.

Methods: Intestinal biopsies were collected from patients and from healthy controls. Circular DNA was enriched, sequenced, identified with Circle Finder, and annotated with bedtools. Patients were then stratified based on disease type and activity.

Results: Intestinal tissue from IBD patients contained significantly higher levels of eccDNAs than tissue from healthy controls. eccDNA production also was significantly increased in patients with active Ulcerative Colitis compared to patients in remission. In Crohn's Disease, eccDNAs were more abundant than in healthy controls, though the difference between active and inactive Crohn's Disease was less defined. Furthermore, eccDNAs containing gene fragments from specific genes were consistently found in a large proportion of patients with IBD, while healthy controls presented with a more stochastic eccDNA pattern.

Conclusions: Here, we uncover an IBD-specific pattern of eccDNA production from intestinal biopsies. Furthermore, we have identified genic hotspots which characterize active disease. We propose that eccDNA containing specific gene fragments (eg, NRG1 and ZPMF2) could represent a promising new biomarker tool for patients with IBD.

Background and aims: In ulcerative colitis (UC), therapeutic goals are evolving beyond symptom control toward endoscopic and histologic healing. However, optimal strategies to achieve these targets are undefined, and the implementation of treat-to-target (T2T) in patients with minimal symptoms despite ongoing intestinal inflammation remains unexplored. This study evaluated the real-world effectiveness of endoscopy-guided optimization in this population.

Methods: TACTIC-UC is a retrospective, single-centre study including UC patients undergoing endoscopy-guided optimization of anti-TNF agents, vedolizumab, or ustekinumab. Eligible cases had quiescent or mild symptoms (partial Mayo score 0-4) but moderate-to-severe endoscopic activity (endoscopic Mayo Score, eMS ≥2) and underwent treatment optimization within 1 month after index endoscopy. The primary outcome was mucosal healing (MH, eMS ≤1) within 1 year. Secondary endpoints included endoscopic remission (ER, eMS = 0), histo-endoscopic mucosal remission (HEMR, eMS = 0 + Nancy Index = 0-1), biomarker trends, steroid use, adverse events, and treatment persistence.

Results: A total of 164 optimization episodes were analysed in 142 patients. The one-year cumulative probabilities of MH, ER and HEMR were 54.2%, 28.8%, and 20.9%, respectively. In weighted analyses, anti-TNF-α therapies outperformed non-anti-TNF-α agents (vedolizumab and ustekinumab pooled together) across all outcomes: 66.3% vs. 45.0% for MH, 39.3% vs. 19.8% for ER, and 33.2% vs. 8.1% for HEMR (all p-values <0.05); consistent trends were confirmed in an exploratory three-arm analysis incorporating synthetic data augmentation. Baseline steroid use and an eMS of 3 were independently associated with reduced probability of achieving endoscopic and histologic outcomes. No safety signals emerged. Endoscopic and histologic outcomes were associated with improved treatment persistence.

Conclusions: In UC patients with quiescent or mild symptoms but active endoscopic inflammation, endoscopy-guided optimization of biologics is effective in achieving deeper inflammatory control, supporting its integration into T2T strategies.

Objective: To critically evaluate the evidence and mechanistic basis for combining exclusive enteral nutrition (EEN) with biologics in adults with Crohn's disease (CD), addressing the gap between strong theory and limited clinical proof.

Methods: We conducted a literature review up to May 2025, focusing on studies combining EEN with biologics (anti-TNF agents, vedolizumab, or Ustekinumab). We assessed methodological quality and bias.

Results: The current literature-mainly small, retrospective cohort studies-indicates that adding EEN to biologic therapy may increase clinical and endoscopic remission rates by 30-50% compared to biologic monotherapy. This effect is believed to be attributed to enhanced mucosal healing, alterations in the microbiome, and improved pharmacokinetics. However, these findings are based on studies with significant limitations, including selection bias, varying protocols, and lack of blinding.

Conclusion: Combined therapy with Exclusive Enteral Nutrition (EEN) and biologics shows promise in managing complex Crohn's Disease (CD), with studies reporting improved remission rates. This clinical benefit may be attributed to a synergistic effect supported by a plausible biological basis. However, these favorable outcomes are based on low-certainty evidence from limited clinical studies. Robust randomized controlled trials are needed to establish the effectiveness, safety, and best use of this combination approach. Keywords: Crohn's disease; Exclusive enteral nutrition; Combination therapy; Biologics; Mucosal healing.

Background and aims: Data on the management of acute severe ulcerative colitis (ASUC) in patients with prior anti-tumor necrosis factor (anti-TNF) exposure are limited. We compared medical management, colectomy risk, and mortality between anti-TNF-exposed and bio-naive patients.

Methods: This retrospective, multicenter GETECCU study included two ASUC cohorts (2010-2020): anti-TNF-exposed (cohort 1) and bio-naive (cohort 2). Patients previously treated with other advanced therapies were excluded. Steroid response was defined by reduced bowel movements and C-reactive protein. Rescue therapies were used for steroid failure. Maintenance therapy was initiated post-ASUC. Clinical effectiveness was assessed using the partial Mayo score (remission ≤2). Colectomy rates were analyzed through survival analysis and Cox regression. Mortality at 12 months was also evaluated.

Results: A total of 461 patients were included: 149 in cohort 1 and 312 in cohort 2. Steroid use was lower in cohort 1 (82% vs 97%, P < .001), but clinical response rates were similar. Rescue therapy rates were comparable (52% vs 57%, P = .88); infliximab use was lower in cohort 1 (25% vs 54%, P < .01). At 12 months, cohort 1 showed lower remission (44% vs 59%, P = .03) and higher colectomy (17% vs 8.7%, P = .01). Overall colectomy was higher in cohort 1 (34% vs 17%; hazard ratio 2.46, P = .001). One-year mortality was 1.52% (no significant differences between cohorts).

Conclusion: ASUC management in anti-TNF-exposed patients is heterogeneous and differs from that of bio-naive patients, with increased risk of treatment failure and colectomy.

Background and aims: Microscopic colitis (MC) is a chronic gastrointestinal disease with disabling symptoms and associated comorbidities. Yet, the economic impact of MC has not been studied. In this cost-of-illness study, we estimated the economic burden of MC.

Methods: We used histopathology reports from all of Sweden's 28 pathology departments to identify 11 517 adult patients with biopsy-proven MC as of January 1, 2017. Each patient was compared to up to five general-population comparators matched on sex, age, and county of residence. Mean costs for the calendar year of 2016 were calculated based on nationwide register data encompassing healthcare use, dispensed medications, and work loss derived from sick leave and disability leave. The number of budesonide treatments following MC diagnosis was used as a proxy for disease activity. Mean differences were further adjusted for education level.

Results: Compared with the general population, patients with MC had an annual mean excess cost of $4805 (USD; adjusted mean difference [95% CI], $4974 [$4650; $5298]), corresponding to a cost ratio of 1.84 (95% CI, 1.74; 1.95). Based on an estimated disease prevalence of ∼0.1%, the economic burden of MC was $1.2 million per 100 000 inhabitants. No significant cost differences were seen based on subtype or sociodemographic factors. However, a high disease activity was associated with higher costs driven by excess work loss.

Conclusion: Compared with the general population, patients with MC had almost twice as high annual mean costs. Excess costs were particularly high in patients with a high disease activity at onset, mainly driven by work loss.

Background and aims: Risankizumab, a selective interleukin-23 p19 inhibitor, is approved to treat moderately to severely active Crohn's disease (CD) in adults. We report interim results from part 2 of the ongoing SEQUENCE trial evaluating long-term efficacy and safety of risankizumab in patients with active CD and previous anti-tumor necrosis factor failure.

Methods: Patients randomized to risankizumab who completed the part 1 Week 48 visit could continue receiving open-label subcutaneous risankizumab 360 mg every 8 weeks (part 2). Patients with inadequate response could receive rescue therapy (intravenous risankizumab 600 mg) before continuing regular treatment. This interim analysis assessed efficacy at Weeks 52, 76, and 100 of treatment; safety was evaluated throughout.

Results: Overall, 224 patients who received risankizumab 600 mg intravenous induction therapy and 360 mg subcutaneous maintenance therapy entered part 2. Clinical remission rates remained stable through Week 100 (as observed, ≥74.5%; nonresponder and modified non-responder imputation analyses showed similar trends). Most patients (>99%) achieving clinical remission were corticosteroid-free at the corresponding visit. CD-related hospitalization and surgery incidence were low (≤0.03 n/patient year), and Inflammatory Bowel Disease Questionnaire and 36-Item Short Form Health Survey improvements were sustained. Safety data were consistent with the known risankizumab safety profile; the exposure-adjusted serious adverse event rate was 11.8/100 patient-years.

Conclusions: This interim analysis of continuous open-label risankizumab therapy showed durable long-term clinical efficacy and no new safety signals in patients with moderately to severely active CD. Future analyses will evaluate longer-term clinical and endoscopic outcomes and safety.

Clinical trial registration number: NCT04524611.