Inflammatory Bowel Diseases最新文献

Ulcerative colitis (UC) is a chronic inflammatory disorder characterized by a significant unmet clinical need for more effective and tolerable therapies. This study explores the therapeutic potential and underlying mechanisms of electroacupuncture (EA) at the Baliao acupoints in a dextran sulfate sodium (DSS)-induced UC rat model. EA treatment significantly alleviated colitis symptoms, restored colon length, and enhanced gut barrier integrity by upregulating tight junction proteins (ZO-1/occludin). Mechanistically, EA activated cholinergic neurons in the dorsal root ganglion (DRG), increased the prevalence of α7nAChR (alpha 7 nicotinic acetylcholine receptor)-positive M2 macrophages in the colon, and elevated local acetylcholine levels. These effects were abolished by the α7nAChR antagonist methyllycaconitine (MLA), confirming the critical role of α7nAChR-mediated cholinergic signaling. Additionally, EA modulated gut microbiota composition, promoting beneficial bacteria (eg Lactobacillus) and suppressing pathogenic species. Heart rate variability analysis indicated enhanced vagal activity post-EA. Collectively, these findings demonstrate that EA at the Baliao acupoints alleviates experimental UC via α7nAChR-dependent facilitation of M2 macrophage polarization and restoration of a healthy gut microbiota, highlighting a promising neuromodulation-based approach for UC treatment.

Background: Gastrointestinal tract inflammation may cause deep alterations of the gut homeostasis, even after the acute phase is resolved. Indeed, there is at present substantial evidence that a considerable percentage of patients with inactive inflammatory bowel disease may experience persistent abdominal symptoms (often resembling those of irritable bowel syndrome) long after the intestinal inflammatory flares had successfully treated and resolved.

Methods: The pertinent literature on this topic was reviewed and critically examined.

Results: Persistent symptoms can be disabling and significantly impair the quality of life, particularly because it is often difficult or impossible to individuate an underlying cause.

Conclusions: Emerging evidence suggests that such pain may result from complex interactions involving visceral hypersensitivity, alterations in the enteric nervous system, central sensitization, dysregulation of the gut-brain axis, and psychosocial factors, rather than ongoing mucosal inflammation. This review explores the multifactorial pathophysiology underlying persistent abdominal pain in inflammatory bowel disease remission and highlights the need for a comprehensive, biopsychosocial approach to diagnosis and treatment.

Background: Ozanimod is a once-daily oral selective sphingosine 1-phosphate receptor modulator approved for the treatment of moderately to severely active ulcerative colitis (UC) or relapsing multiple sclerosis (RMS). Previous analyses in both indications demonstrated favorable long-term safety profiles of ozanimod. Here we report an integrated analysis of the long-term safety of ozanimod in patients with UC or RMS.

Methods: Data were pooled in patients with UC who received ozanimod in phase 2, phase 3, and open-label extension (OLE) trials and in patients with RMS who received ozanimod in an OLE trial after completing any phase 1-3 parent trial. Safety assessments included treatment-emergent adverse events (TEAEs) and laboratory abnormalities.

Results: Overall, 3652 patients with UC or RMS had 16 144 patient-years (PY) of ozanimod exposure over 10 years of follow-up. The most common TEAEs were nasopharyngitis, headache, and coronavirus disease 2019. Rates of TEAEs leading to treatment discontinuation (1.4/100 PY) and TEAEs of special interest, including serious infections (1.0/100 PY), herpes zoster (0.5/100 PY), malignancies (0.4/100 PY), bradycardia (0.1/100 PY), sinus bradycardia (0.04/100 PY), complete atrioventricular block (0.01/100 PY), and macular edema (0.1/100 PY), were low. No serious hepatic events or Hy's law cases occurred. Absolute lymphocyte count of < 200 cells/µL was not temporally associated with serious or opportunistic infections.

Conclusions: Long-term exposure to ozanimod is well tolerated in patients with moderate to severe UC or RMS, confirming the previously established safety profile of ozanimod.

Clinical trial registry: NCT01647516; NCT02435992; NCT02576717.

Importance: Data on advanced therapy (AT) in patients with HIV and inflammatory bowel disease (HIV-IBD) are limited. Objective We evaluated the safety and outcomes of AT in this population using real-world data.

Design, setting, and participants: We conducted a retrospective cohort study in the TriNetX database (2015-2020). Adult patients with HIV-IBD on anti-retroviral therapy were identified using ICD-10 codes. Propensity score matching (PSM) adjusted for baseline clinical and demographic differences. Intervention(s) or Exposure(s) AT exposure identified via prescription codes of biologics or small molecules. Main Outcomes and Measures Primary outcomes were serious infections, opportunistic infections, and incident cancers; secondary outcomes included IBD-related surgery and all-cause mortality.

Results: Among 3422 patients with HIV-IBD, 173 (5.05%) received AT. The most commonly used agents were infliximab (41.6%), adalimumab (36.4%), and ustekinumab (11.6%). Mean follow-up was 4.86 years (9861 patient-years). In the unmatched -cohort, rates of serious infections (34.1% vs 36.9%, OR 0.86, P = .14) and opportunistic infections (26.6% vs 26.9%, OR 0.99, P = .94) were similar between patients receiving AT and those not receiving AT. After PSM (163 matched pairs), no significant differences were observed in serious infections (34.3% vs 35.6%, OR 0.85, P = .26), opportunistic infections (24.5% vs 28.2%, OR 0.83, P = .45), malignancy rate, IBD-related surgery, or mortality. Kaplan-Meier analyses showed no statistically significant differences in the cumulative incidence of infections or mortality between groups.

Conclusions and relevance: In this large multicenter cohort, AT use in HIV-IBD was rare but not associated with higher risks of infection, cancer, surgery, or death. These findings support the safety of AT in this population.

Background: Acute severe ulcerative colitis (ASUC) is defined by the Truelove and Witts (TW) criteria. However, contemporary practice has shifted toward earlier admission and treatment escalation in advanced therapy-experienced patients, resulting in a growing subgroup hospitalized for ASUC who do not fulfill TW (non-TW ASUC). This population remains poorly characterized.

Methods: Retrospective cohort study of all patients hospitalized for ASUC and treated with intravenous corticosteroids at a Danish tertiary center until 2023. The primary outcome of 1-year colectomy was assessed in an independent validation cohort.

Results: Of 109 included patients, 80 (73%) fulfilled TW criteria and 29 (27%) did not. Non-TW ASUC patients were less often female (28% vs 63%; P < .01), were less frequently steroid-naïve (21% vs 48%; P < .05), and presented with lower systemic inflammation (C-reactive protein median 7 mg/L vs 34 mg/L; P < .001; hemoglobin 13.7 g/dL vs 12.2 g/dL; P < .001; albumin 41 g/L vs 38 g/L; P < .001). Colectomy-free survival and colectomy rates at 1, 3, and 12 months were comparable between non-TW and TW ASUC (14% vs 10%, 21% vs 16%, and 29% vs 19%, respectively; P > .05). Results were similar in the validation cohort (n  = 43). Medical rescue therapy use, tumor necrosis factor inhibitor exposure, and readmission rates through 1 year did not differ significantly. Prognostic indices (Ho, Lindgren, Travis) similarly identified high-risk patients across both groups. Non-TW patients had shorter hospital stay (mean 6.5 days vs 8.6 days; P < .01).

Conclusion: Non-TW ASUC shows a disease course and outcomes comparable to TW ASUC, underscoring an equally severe and comparable condition. These findings emphasize a need to broaden ASUC definitions to reflect contemporary practice.

Background and aims: Up to 70%-80% of patients with primary sclerosing cholangitis (PSC) will have concomitant inflammatory bowel disease (IBD). Scarce data are available regarding outcomes of advanced therapies to treat IBD-PSC. We performed a systematic review and meta-analysis to assess the effectiveness and safety of advanced therapies in IBD-PSC.

Methods: A systematic search was conducted in Cochrane Library, Embase, Google Scholar, Ovid Medline, PubMed, Scopus, and Web of Science from database inception to January 29, 2025. We included studies that reported on IBD clinical response with advanced therapies. Meta-analysis was performed using the random effects model. Subgroup analyses were conducted to further investigate proportion differences between covariates.

Results: Nineteen studies (n = 864) were included in the final analysis. Among IBD-PSC patients treated with advanced therapies, clinical response was observed in 52% (95% CI, 40%-65%; I2 = 85%), clinical remission in 43% (95% CI, 25%-62%; I2 = 91%), and endoscopic remission in 26% (95% CI, 13%-42%; I2 = 75%). Infections occurred in 22% of patients (95% CI, 8%-40%; I2 = 82%) and acute cholangitis was observed in 14% of patients (95% CI, 2%-33%; I2 = 80%). The endoscopic remission rate with anti-tumor necrosis factor (anti-TNF) agents was 29% (95% CI, 10%-52%; I2 = 28%) vs. 15% (95% CI, 4%-29%; I2 = 70%) in those who received non-anti-TNF biologics. The rates of overall infections were similar in patients who received anti-TNF vs. non-anti-TNF biologics.

Conclusions: Advanced therapies show efficacy and comparable safety in IBD-PSC. The study findings are limited by significant heterogeneity and further prospective studies with standardized endpoints are needed.

Background: We aimed to build a serum proteomics-based model to predict primary nonresponse (PNR) to infliximab (IFX) in pediatric colonic inflammatory bowel disease, with early proactive therapeutic drug monitoring.

Methods: Children in the prospective Canadian Children IBD Network with ulcerative colitis (UC), inflammatory bowel disease unclassified (IBD-U), or colonic Crohn's disease (CD) with serum pre-IFX were eligible. We defined PNR as IFX cessation plus surgery/drug switch within 6 months. We compared clinical features between groups (Mann Whitney U, chi-square test). We measured serum proteins with Olink Inflammation/Immune Response panels. We built a regularized regression (generalized linear model [GLM]) machine learning model and compared its performance with other models with 10-fold cross-validation repeated 10 times (receiver-operating characteristic/precision-recall curves, predictive score separation). We ranked proteomic features by SHAP (SHapley Additive exPlanations) analysis. We hypothesized that treatment-naïve serum would be more informative than treatment-exposed serum.

Results: We included 96 patients: 71 UC/IBD-U (23 nonresponders), 42 treatment-naïve (12 nonresponders); and 25 CD, 19 treatment-naïve. Pre-third and pre-fourth dose serum infliximab levels were similar and robust (>10 µg/mL) in primary nonresponders and responders. Predictive performance was superior for diagnostic, treatment-naïve samples; the GLM showed good ability to separate primary nonresponders and responders. The GLM model on treatment-naïve serum (area under the curve ∼0.75) had better specificity to predict responders and included 21 proteins, with CSF1 and ITM2A top ranked. UC/IBD-U responders more often were steroid refractory and received infliximab as first maintenance.

Conclusions: A serum proteomics linear model on treatment-naïve serum best predicted PNR. Findings require external validation but suggest that the diagnostic/pretreatment window may be key to understanding biology central to effective drug sequencing.

The expanding therapeutic landscape of inflammatory bowel disease has highlighted the need for clear and standardized drug nomenclature to support safe prescribing, pharmacovigilance, international communication, and patient understanding. The World Health Organization's international nonproprietary name system, established in 1953, assigns unique and informative names to medicines. However, the increasing number and diversity of monoclonal antibodies used in inflammatory bowel disease and other diseases have outgrown the capacity of the traditional -mab suffix to convey meaningful structural or functional distinctions. In 2021, the international nonproprietary name system was updated to introduce new suffixes, such as -tug, -bart, -ment, and -mig, that provide more precise information, although these remain unfamiliar to many clinicians. This narrative review explores how international drug naming conventions have evolved and have been applied within the context of inflammatory bowel disease, from early compounds to contemporary engineered therapies, and examines the rationale and clinical relevance of the updated naming framework. Drawing on historical and current literature, as well as policy documents from the World Health Organization's international nonproprietary name expert group, this review charts the development and successive reforms of the naming scheme. As inflammatory bowel disease therapies continue to diversify, understanding this evolving nomenclature is increasingly important for safe prescribing and effective communication.

Background and aims: Clinicians need data on the responsiveness of ileal strictures of Crohn's disease (CD) to biologic therapy, yet most trials prioritize mucosal healing. We quantified short‑term changes in ileal strictures under biologic treatment and evaluated their prognostic relevance.

Patients and methods: In a post hoc analysis of a prospective cohort, consecutive patients with ileal or ileocolonic CD initiating or switching a biologic (anti‑tumor necrosis factor [TNF], ustekinumab [UST], or vedolizumab [VDZ]) underwent segment‑specific endoscopic assessment at baseline and 6 months. The primary outcome was resolution or progression of strictures at 6 months. Secondary outcomes included time‑to‑event analyses for hospitalization and surgery.

Results: Among the 170 patients, the 6‑month stricture resolution and progression rates were 30.9% and 15.7%, respectively. There were no significant differences in stricture dynamics between anti‑TNF agents, UST, and VDZ (P = .443 for resolution and P = .167 for progression). Baseline strictures did not predict outcomes; however, strictures present at 6 months were associated with higher risks of hospitalization (P = .006) and surgery (P = .024), particularly when located in the non-terminal ileum. Clinical, biochemical, and endoscopic activity improved overall during follow‑up.

Conclusions: The 6‑month stricture status, especially non-terminal ileal disease, carried prognostic significance. Because stricture dynamics did not differ across biologic classes, the presence of strictures alone should not constrain agent selection.