Journal of Crohn's & colitis最新文献

Background and aims: Upadacitinib (UPA)-an oral, reversible selective Janus kinase inhibitor-has a favorable benefit-risk profile for patients with Crohn's disease (CD) and ulcerative colitis (UC). We evaluated the benefit-risk of UPA in select subgroups with CD or UC.

Methods: Patients were randomized to UPA 45 mg (UPA45) once daily (QD) or placebo (PBO) induction for 12 (CD: U-EXCEED, U-EXCEL) or 8 weeks (UC: U-ACHIEVE, U-ACCOMPLISH). Clinical responders were re-randomized to QD UPA 15 mg (UPA15), UPA 30 mg (UPA30), or PBO for 52-week maintenance (CD: U-ENDURE; UC: U-ACHIEVE). This exploratory post hoc analysis assessed efficacy and safety outcomes (adverse events of special interest [AESIs]: serious infections, major adverse cardiovascular [CV] events, malignancies, and venous thromboembolic events) by CV risk, prior treatment failure, and age.

Results: This analysis included 1021 patients with CD and 1097 with UC during induction, and 673 with CD and 746 with UC during maintenance. Improved efficacy outcomes comparable to the overall study populations were observed with UPA versus PBO across subgroups. Patients receiving UPA30 generally showed numerically higher rates of improvements versus UPA15. AESI rates were generally comparable between UPA and PBO across subgroups except for numerically higher rates of herpes zoster and serious infections in CD with UPA.

Conclusions: UPA resulted in consistent benefit versus placebo across CV risk, prior treatment failure, and age subgroups. No treatment differences were seen in AESIs across subgroups except herpes zoster and serious infections, reinforcing the favorable benefit-risk profile for UPA in CD and UC seen in the overall study populations.

Clinical trial numbers: NCT02819635, NCT03653026, NCT03345836, NCT03345849, NCT03345823.

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.

Background: Achieving endoscopic remission is a key therapeutic goal in IBD that is associated with improved disease outcome. Transmural and intestinal barrier healing represent emerging targets, as they have similarily been associated with favourable disease behaviour. To date, no study has compared these novel endpoints 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 (MRI) or intestinal ultrasonography (IUS). 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: 80 patients (47 CD, 33 UC) were included. During a mean FU of 34 (CD) and 18 (UC) months, 72% of CD and 85% of UC patients experienced MAO. Intesinal 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 progession 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 endpoints potentially refining disease monitoring and outcome prediction.

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: The aim of this nationwide population-based cohort study was to examine an association between previous open and laparoscopic abdominal surgery for inflammatory bowel disease (IBD) and adverse pregnancy and birth outcomes.

Methods: From the Danish Medical Birth Registry, we identified women with Crohn's disease (CD) and ulcerative colitis (UC), who had given birth between 1997 and 2024. We compared risk of adverse pregnancy and birth outcomes between women with and without prior abdominal surgery using adjusted odds ratios (ORs) with 95% confidence intervals.

Results: We identified 12,894 pregnancies among women with IBD (5,201 CD; 7,693 UC). In 2,070 (16.1%) pregnancies, at least one abdominal operation had been performed prior to conception. In CD pregnancies, prior surgery was associated with an increased risk of elective cesarean section (adjusted OR [aOR] = 1.68, 95% CI: 1.43-1.97). In UC pregnancies, prior surgery was associated with an increased risk of prematurity (aOR = 2.92, 95% CI: 2.25-3.76), preterm elective and emergency cesarean section (aOR = 6.99, 95% CI: 3.46-13.9 and aOR = 3.46, 95% CI: 2.34-5.04), elective cesarean section (aOR = 11.2, 95% CI: 9.23-13.5), low birth weight (< 2.500 grams: aOR = 1.99, 95% CI: 1.46-2.67) and neonatal intensive care (aOR = 4.10, 95% CI: 1.64-9.78). Laparoscopic surgery was not associated with fewer adverse pregnancy or birth outcomes compared to open surgery.

Conclusion: Prior surgery for IBD is associated with an increased risk of adverse pregnancy and birth outcomes. A laparoscopic approach does not mitigate these risks.