Introduction: Ustekinumab (UST) and vedolizumab (VED) are effective for ulcerative colitis (UC), but long-term real-world data, particularly regarding endoscopic remission, remain limited. Methods: Patients with UC who were treated with UST or VED at two tertiary centers were enrolled in this retrospective study. Baseline imbalances were adjusted using inverse probability of treatment weighting. The primary outcome was the endoscopic remission rates (Mayo Endoscopic Subscore [MES] 0 or 1, and MES 0 alone) at 1 year and 2 years. Secondary outcomes included clinical remission rates and treatment persistence. Results: Overall, 197 patients were analyzed; 96 received UST, and 101 received VED. The median observation period was 2.5 years. Clinical remission rates did not differ between the two groups. Treatment persistence was higher with UST than with VED (HR 1.85; 95% CI, 1.13–3.02; p = 0.014), particularly in the early period. At 1 year, there were no significant differences in endoscopic remission rates for MES 0 or 1 and MES 0 alone between the two groups. At 2 years, patients treated with UST were significantly more likely to achieve MES 0 or 1 (UST, 45.0% vs VED, 19.8%; OR for VED vs UST, 0.30; 95% CI, 0.11–0.82; p = 0.019), whereas achievement of MES 0 alone did not differ significantly. Conclusion: UST was associated with a higher rate of achieving MES 0 or 1, while deep remission rates were comparable. This may explain a more pronounced difference in treatment persistence in the short-term phase, with the difference decreasing over time.

Introduction: Real-world data on the long-term effectiveness of vedolizumab (VED) in East Asian patients with Crohn’s disease (CD) remain limited. This study aimed to assess treatment persistence, clinical and endoscopic effectiveness, safety, and predictors of VED discontinuation in a multicenter Japanese cohort. Methods: A retrospective study was conducted across seven hospitals between June 2019 and October 2025, including patients with CD who initiated VED. Outcomes included VED continuation, factors associated with discontinuation, longitudinal changes in clinical and endoscopic indices, and adverse events. Results: Seventy-three patients were included. VED continuation was 62.3% and 37.8% at 1 and 3 years, respectively. In a multivariable Cox analysis, higher baseline C-reactive protein (CRP), higher body mass index (BMI), and female sex were independently associated with increased risk of VED discontinuation, with a trend toward better persistence among patients with ileal disease. In the 1-year analysis, female sex and prior biologic exposure predicted early discontinuation. CD activity index and its subscores improved during early treatment, and albumin levels increased gradually over time. Simple endoscopic score for CD improved at 1 and 2 years. Among patients with active disease, >40% achieved remission from week 6 onward. Adverse events occurred in 16.4%, with two (2.7%) patients discontinuing VED due to infusion reactions or psoriasiform rashes. Conclusion: VED demonstrated acceptable long-term durability, clinically meaningful and endoscopic improvement, and a favorable safety profile in Japanese real-world practice. Baseline CRP, BMI, sex, and prior biologic exposure were important predictors of treatment persistence.

Introduction: Histological remission is the most predictive endpoint in inflammatory bowel disease (IBD), yet repeated biopsies are invasive. Interleukins (ILs) are emerging biomarkers that may capture histology-aligned activity. We systematically evaluated IL-6, IL-23, IL-17A, IL-1β, IL-8, and IL-10 as diagnostic and prognostic biomarkers in ulcerative colitis (UC) and Crohn’s disease (CD). Methods: MEDLINE, EMBASE, and Web of Science were searched (January 1995–March 2025). Eligible studies quantified ILs in serum, plasma, stool, or tissue and reported diagnostic/prognostic outcomes against validated histology indices. Risk of bias was assessed with QUADAS-2 (diagnostic) and QUIPS (prognostic). Certainty was graded using GRADE. Due to assay heterogeneity, narrative synthesis was performed. Results: Sixty-four adult cohorts were included. Serum IL-6 (AUC 0.82–0.85; sensitivity/specificity ≈75–80%) and IL-23 (AUC 0.84–0.86; specificity up to 92%) consistently discriminated histological activity. Tissue IL-23/IL-17A aligned with neutrophils, crypt injury, and apoptosis, detecting subclinical inflammation and forecasting relapse (notably in ileal CD). IL-1β/IL-8 modestly reflected neutrophil-rich lesions. IL-10 inversely correlated with activity and higher remission levels predicted longer flare-free survival. Conclusion: IL-6 and IL-23 are the strongest serum biomarkers for histology-aligned activity; tissue IL-17A adds lesion-level resolution, while IL-10 provides prognostic value. Interleukin profiling complements CRP and fecal calprotectin, with its immediate role in precision-medicine stratification rather than replacement of current standards. Key Messages:Histological remission is the most reliable endpoint in inflammatory bowel disease but requires invasive biopsies. Interleukin profiling offers a biologically specific, noninvasive alternative that aligns with histological activity. Among candidate cytokines, serum IL-6 and IL-23 consistently show the strongest diagnostic performance, while tissue IL-17A enhances lesion-level resolution and IL-10 provides prognostic value for remission stability. Interleukin signatures therefore complement C-reactive protein and fecal calprotectin, supporting precision-medicine strategies for individualized monitoring and therapy optimization in IBD.

Introduction: Improvement of small intestinal lesions is essential for achieving favorable long-term outcomes in patients with Crohn’s disease (CD); however, evidence regarding the efficacy of biologics for small bowel involvement remains limited. Risankizumab (RZB), a selective interleukin-23 (IL-23) p19 inhibitor, has shown efficacy in large randomized trials; however, data on its effect on small intestinal inflammation are limited. This study aimed to evaluate the real-world effectiveness of RZB on small intestinal lesions using balloon-assisted enteroscopy. Methods: We retrospectively analyzed 23 patients with CD who received RZB between July 2023 and January 2025. Clinical activity was assessed using the Harvey–Bradshaw Index (HBI), and serum biomarkers (albumin, C-reactive protein, and hemoglobin) were measured longitudinally. Endoscopic activity was evaluated using the Simple Endoscopic Score for CD (SES-CD) before treatment and at 28 weeks after treatment; paired endoscopic assessment was available in 16 patients. Results: At baseline, 10 patients had clinically active disease (HBI ≥4), and 13 were in clinical remission (HBI ≤3). In the active group, HBI and C-reactive protein levels significantly decreased after treatment, whereas hemoglobin and albumin concentrations increased during follow-up. Among the 16 patients who underwent paired endoscopic evaluation, both total and ileal SES-CD scores significantly decreased after 28 weeks of RZB therapy, demonstrating mucosal improvement in the small intestine. Notably, several patients who showed inadequate response to ustekinumab (UST) also exhibited endoscopic improvement after RZB treatment. Conclusions: RZB was effective in improving clinical and endoscopic disease activities, including small intestinal lesions, even in patients who were previously refractory to UST. Given the prognostic importance of small bowel inflammation, these findings highlight the potential of selective IL-23p19 inhibition as a valuable therapeutic option for patients with small bowel-dominant CD.

Introduction: Achieving both endoscopic and histological remission in ulcerative colitis (UC) is associated with improved clinical outcomes. There is a growing need for noninvasive methods to assess both remission states. This study investigates the utility of serum leucine-rich alpha-2 glycoprotein (LRG) as a biomarker for monitoring endoscopic and histological remission in patients with UC. Methods: Patients with UC who underwent colonoscopy from July 2020 to September 2021 at multiple centers in Japan were included to compare the accuracy of C-reactive protein (CRP) and LRG in detecting endoscopic and histological remission. Receiver operating characteristic curve analyses were performed and area under the curve (AUC) values were compared. Results: A total of 412 patients were identified. The median values of CRP and LRG were 0.07 mg/dL and 12.2 μg/mL, respectively. Endoscopic remission, as defined as Mayo endoscopic sub-score of 0 or 1, was observed in 188 patients, and histological remission, as defined as Geboes score <3.1, was observed in 156 patients. The AUC values for CRP and LRG for detecting endoscopic remission were 0.68 and 0.76, respectively, and the AUC values for CRP and LRG for detecting histological remission were 0.70 and 0.76, respectively. In both cases, the AUC for LRG was significantly higher than that of CRP (p < 0.0001). The optimal cutoff value of LRG for detecting histological remission was 13.4 μg/mL, with a sensitivity of 82% and a specificity of 58%. Conclusion: LRG is superior to CRP in detecting both endoscopic and histological remission in patients with UC.

Long-term Crohn's disease (CD) increases risk of cancer. However, data on the clinical characteristics and optimal endoscopic surveillance strategies for CD-associated cancers in Japan remain controversial. This study aimed to investigate the clinical characteristics, diagnostic methods, and treatment patterns of CD-associated cancers at our institution and to consider strategies for effective surveillance in Japanese clinical practice. We retrospectively analyzed 21 patients with 26 CD-associated cancer locations treated at our hospital between August 2001 and March 2024, focusing on their clinical backgrounds, cancer characteristics, and endoscopic surveillance practices. Anorectal cancer was the most common (61%), and 57% were stage II or higher at the time of diagnosis. There were 12 cases of fistula-associated cancer, with a median disease duration of 18.5 years, and 7 cases of stage II or higher. Targeted endoscopic biopsy established the diagnosis in 77%, often requiring multiple-site biopsies. Remission or mild endoscopic activity was observed in 75% (6/8) of stage 0-I patients, compared with 20% (2/10) of stage II-IV patients, suggesting a trend toward more advanced cancer with higher endoscopic activity (p = 0.03). Compared with non-anorectal cancers, 33% of anorectal cancers required four or more endoscopic biopsies for diagnosis, and this rate was significantly higher than that of non-anorectal cancers (p = 0.028). Anorectal cancer was the most common CD-associated cancer, and strictures and active inflammation made early diagnosis difficult. Annual surveillance with multiple-site biopsies of anal lesions was essential.

Background: Since the late 1990s, eosinophilic esophagitis (EoE) became a known disease characterized by eosinophilic infiltration into the esophagus accompanied by esophageal symptoms. Over the past 2 decades, there has been an exponential increase in the understanding of the epidemiology and pathogenesis of disease leading to new therapies. Despite this, we still have significant knowledge gaps in our clinical care. Summary: Despite a plethora of knowledge gained about EoE over the last 3 decades, medical care of EoE continues to struggle with uncertainties. Presently, we lack available methods to predict who is at risk of complications or who will be refractory to therapy. There is only a paucity of data about how to maintain long-term control of inflammation, and we have yet to develop clinically applicable biomarkers to predict clinical phenotypes (i.e., those who will recur while on therapy). This review focuses on a few of the common limitations in current care of EoE: (1) diagnosis, (2) accurate food antigen testing, (3) prediction of clinically relevant phenotypes, (4) maintenance and surveillance strategies, (5) optimal disease endpoints, and (6) need for less invasive monitoring. Key Messages: Despite rapid increase in our comprehension of EoE, patients continue to have unmet needs. However, with the continued rapidity of investigation, many of these current deficiencies are being addressed and will likely be resolved in the future.

Background: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory disease affecting the esophagus, characterized by esophageal dysfunction, dysphagia, and tissue remodeling, leading to significant impairment in quality of life. The pathogenesis of EoE involves a complex interplay of genetic, environmental, and immunological factors. Although the disease is strongly associated with type 2 immune responses, emerging evidence suggests that B cells and antibody responses, particularly IgG4, also play a crucial role in disease development and progression. Summary: This review explores the pathogenesis of EoE with a focus on the role of B cells, plasma cells, and antibodies. Epithelial barrier dysfunction is a pivotal factor in EoE, influenced by genetic predisposition, environmental triggers, and immune responses. The impaired barrier allows for antigen penetration, triggering type 2 immune responses, and chronic inflammation. Elevated levels of IgG4 in esophageal tissues and their potential to drive inflammation and tissue remodeling are highlighted. Animal models and clinical studies provide insights into the involvement of B cells and antibodies in EoE, suggesting that these components may contribute to the chronic inflammatory state and disease severity. Key Messages: B cells are increasingly recognized for their role in EoE, particularly through their production of antibodies and cytokines that contribute to the inflammatory milieu. EoE is primarily driven by type 2 immune responses involving cytokines such as IL-4, IL-5, and IL-13, which promote eosinophil recruitment and chronic inflammation. Regulatory B cells, which produce anti-inflammatory cytokines such as IL-10 and IL-35, may play a role in modulating immune responses in EoE and contribute to the production of IgG4 antibodies. Elevated levels of IgG4 in esophageal tissues of EoE patients are linked to chronic inflammation and tissue remodeling, suggesting a potential role in disease pathogenesis. Further studies are needed to elucidate the specific mechanisms by which B cells and antibodies contribute to EoE.

Physical activity levels are often lower in people with inflammatory bowel disease (IBD) than in healthy individuals. However, no studies have examined physical activity levels and associated factors among Japanese people with IBD. This study aimed to examine physical activity levels and their associations with other factors, including disease activity and quality of life (QOL). A nationwide online survey was conducted through an online community for people with IBD. Physical activity was assessed using the short version of the International Physical Activity Questionnaire and classified into low and moderate-to-vigorous intensity groups based on World Health Organization guidelines. Disease activity was evaluated using the Simple Clinical Colitis Activity Index (SCCAI) for ulcerative colitis and the Harvey-Bradshaw Index (HBI) for Crohn's disease. QOL was measured using the Inflammatory Bowel Disease Questionnaire-32 (IBDQ-32). Binary logistic regression was used to identify factors associated with physical activity level, and simple linear regression to evaluate associations between physical activity and both disease activity and QOL. Overall, 232 participants (mean age 39.9 years, 62.1% women) completed the survey, with 45.3% in the low intensity group and 54.7% in the moderate-to-vigorous intensity group. Most participants were in remission or had mild disease activity (mean SCCAI score 2.85; mean HBI score 4.40). The median weekday sitting time was 420 min/day. None of the demographic, physical, or social support variables were significantly associated with physical activity level. Physical activity level was not significantly associated with disease activity in either ulcerative colitis (p = 0.24) or Crohn's disease (p = 0.50) but had a significant positive association with IBDQ-32 total score (p = 0.03) and the emotional function (p = 0.03) and social function (p = 0.04) subscales. Physical activity levels among Japanese people with IBD were similar to those in other countries, but sitting time was longer. In our study population, who mostly had no more than mild disease, physical activity was not adversely associated with disease activity and had positive associations with emotional and social QOL. We suggest that physical activity can therefore be safely recommended to this population, with implications for nursing practice.

Introduction: Eosinophilic colitis (EoC) is an immune-mediated disorder characterized by chronic colitis with significant eosinophilic infiltration. Diagnosing EoC is sometimes challenging due to more common disorders associated with colonic eosinophilia like inflammatory bowel disease (IBD). This study aimed to examine the prevalence and clinical features of patients who were initially diagnosed with IBD and later found to have EoC (IBD-EoC) and to identify the clinical factors facilitating a definitive EoC diagnosis. Methods: Medical records of patients with eosinophilic gastrointestinal diseases (EGIDs) were retrospectively reviewed and subsequently analyzed for the cases of IBD-EoC. Clinical characteristics were compared between patients with IBD-EoC and those initially diagnosed with EoC (definitive EoC). Results: Among 42 patients with EGIDs, 4 were diagnosed with EoC. Two of them were definitive EoC, while the remaining 2 were initially diagnosed with IBD (IBD-EoC), representing 0.64% of patients with IBD. Unlike in patients with definitive EoC, the endoscopic findings atypically suggestive of IBD and the possibility of EoC were not communicated between the endoscopists and the pathologists in patients with IBD-EoC. The absence of mucosal eosinophil count in the initial histologic report further delayed the diagnosis of EoC. Treatment failure with 5-ASA prompted the reassessment of endoscopic and histologic findings, leading to the revised diagnosis of EoC. The presence of peripheral blood eosinophilia facilitated the initial diagnosis with EoC in patients with definitive EoC. Conclusion: Proactive communication between endoscopists and pathologists is crucial for diagnosing EoC.