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 Increased expression of the epithelial-specific adhesion molecule integrin αvβ6 and the presence of anti-αvβ6 autoantibodies (V6 Ab) have been reported in ulcerative colitis (UC). However, the influence of single-nucleotide polymorphisms (SNPs) in the ITGAV gene on antibody titers, as well as their association with relapse in patients with mild disease, have not been fully elucidated. This study aimed to clarify the impact of ITGAV gene polymorphisms on serum V6 Ab levels in patients with UC. As secondary objectives, we evaluated the association between these SNPs and 1-year relapse and assessed the relapse predictive performance of V6 Ab levels using receiver operating characteristic (ROC) analysis. Methods We retrospectively analyzed 61 patients with UC whose V6 Ab levels were measured at our institution between January 2023 and June 2025. Associations between four ITGAV SNPs (rs3911238, rs3768777, rs1448427, and rs10174098) and V6 Ab levels were examined. Among 49 patients with a partial Mayo score of 0 or 1, we evaluated the relationship between SNP variants and 1-year relapse. The predictive ability of V6 Ab for relapse was assessed using ROC analysis. Results For all four ITGAV SNPs, carriers of variant alleles exhibited significantly higher serum V6 Ab levels compared with wild-type individuals. Among 49 patients with a partial Mayo score of 0 or 1, 14 (28.6%) experienced relapse within 1 year. The relapse group showed significantly higher frequencies of rs3768777, rs10174098, and rs1448427 variants than the non-relapse group. The predictive performance of V6 Ab levels for relapse yielded an area under the ROC curve of 0.78 (95% confidence interval: 0.64–0.89). At a threshold of 6.58 U/mL, sensitivity, specificity, and negative predictive value were 1.00, 0.54, and 1.00, respectively. Conclusion ITGAV gene polymorphisms determined inter-individual variation in V6 Ab levels, with variant carriers exhibiting higher antibody titers and increased risk of relapse. Low V6 Ab levels were a reliable indicator for excluding relapse. The combined use of antibody titers with ITGAV SNP information may facilitate precision stratification of patients with UC in remission or with mild disease.

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.

Introduction: Moderate-to-severe ulcerative colitis (UC) is commonly treated with oral corticosteroids. However, in cases of oral corticosteroid failure, no clear consensus exists on whether to transition to intravenous corticosteroids (IVCS) or initiate advanced therapies. The aim of this study was to evaluate whether responsiveness to oral corticosteroids is associated with differences in the efficacy of IVCS. Methods: This multicenter cohort study (conducted at 10 facilities) included patients with moderate-to-severe UC who were transitioned to IVCS after failure of oral corticosteroid therapy. The patients were categorized into the partial responder and nonresponder groups based on their response to oral corticosteroids, as measured by improvements in their PRO-2 scores. The primary outcome was clinical remission at day 30, defined as a total PRO-2 score ≤1 with a rectal bleeding subscore of 0. Logistic regression was used to estimate the odds ratio (OR) of achieving clinical remission. Results: A total of 123 patients with UC were included, with 41 and 82 patients in the partial responder and nonresponder groups, respectively. Clinical remission at day 30 was achieved in 41.4% of the partial responders and 18.3% of the nonresponders (multivariable-adjusted OR, 0.35 [95% CI: 0.15–0.83]; p = 0.017). The nonresponder group had a higher risk of requiring advanced therapies within 90 days than the partial responder group (multivariable-adjusted OR, 2.48 [95% CI: 1.09–5.66]; p = 0.030). Conclusions: In patients with UC and oral corticosteroid failure, responsiveness to oral corticosteroids may be associated with differences in IVCS efficacy.

[This corrects the article DOI: 10.1159/000546858.].

Introduction: Both mesalazine and ozanimod are oral treatment options for patients with moderately active ulcerative colitis (UC). Methods: Comparative analysis comparing efficacy endpoints of an 8-week non-inferiority induction study (TP0503) with 3.2 g/day mesalazine (n = 321) to the True North 10-week induction study of 1 mg/day ozanimod (n = 281). We compared the efficacy of oral mesalazine (Asacol) as monotherapy and ozanimod (Zeposia) as add-on therapy to mesalazine, without concomitant corticosteroids, following induction treatment in mesalazine-exposed but immunomodulator- and advanced therapy-naïve UC patients. Endpoints from the non-inferiority study were re-calculated using the definitions from the True North study. Results: The two cohorts had similar age (45 ± 14 years vs. 44 ± 13.5 years) and baseline disease severity (total Mayo score; 8.5 ± 0.8 vs. 8.6 ± 1.1) for mesalazine- and ozanimod-treated patients, respectively. No differences were observed in patients achieving clinical response (reduction from baseline in the 3-component Mayo score [sum of rectal bleeding subscore/RBS, stool frequency subscore/SFS, and Mayo endoscopic score/MES) of ≥2 points and ≥35%, and a reduction from baseline in the RBS of ≥1 point or an absolute RBS ≤1} (58% vs. 58%; p = 0.917) and clinical remission (RBS = 0, SFS ≤1 [and decreases of ≥1 point from baseline SFS], and MES ≤1) (22% vs. 28%; p = 0.074) treated with mesalazine (at 8 weeks) and ozanimod (at 10 weeks), respectively. A higher percentage of patients treated with ozanimod achieved endoscopic improvement (MES ≤1 without friability) compared to mesalazine (38% vs. 29%, p = 0.018). Conclusion: Among individuals previously exposed to mesalazine, a similar effect on clinical efficacy was observed between patients treated with mesalazine and those treated with ozanimod.

Introduction: It is crucial to predict the effectiveness of advanced therapies before their administration in ulcerative colitis (UC). Only a few studies have revealed predictive histological factors. Here, we sought to determine whether conventional histology of pretreatment endoscopic biopsy specimens can predict the response to integrin inhibitors. Methods: In the present single-center retrospective study, we examined histopathological findings before initiating an integrin inhibitor. Primary response (PR) was defined as a ≥3-point decrease in the partial Mayo score at 14 weeks. Logistic regression was used to identify the factors predictive for a PR. Results: We analyzed 21 biological and Janus kinase inhibitor-naïve patients with UC. The median baseline Mayo score was 7 (IQR, 6–8), and the C-reactive protein was 0.36 (IQR, 0.11–0.74). Histological findings included large lymphoid follicles (LF) in 61.9% (13/21), basal plasma cell infiltration in 52.4% (11/21), and eosinophilic infiltration (EO) in 42.9% (9/21). PR at 14 weeks was achieved in 57.1% (12/21). Among PR patients, LF was present in 91.7% (11/12), BP in 41.7% (5/12), and EO in 25.0% (3/12). PR was observed in 76.9% (10/13) of LF-positive patients vs. 12.5% (1/8) of LF-negative patients (p = 0.01). LF was significantly associated with the response to integrin inhibitors, whereas BP and EO were not. Conclusion: The presence of LF in biopsy specimens predicts the response to integrin inhibitors in patients with UC. Conventional histological examinations may aid in predicting therapeutic responses to advanced therapies.

Background: For both men and women, family planning, including decisions regarding marriage and childbearing, is a significant life event that contributes to overall “happy life.” Patients with chronic diseases such as inflammatory bowel disease face not only concerns about common pregnancy-related complications but also disease-specific challenges, including the potential effects of medications on the fetus and the risk of disease exacerbation during pregnancy. In response to these concerns, patients may occasionally make misguided decisions, such as the self-discontinuation of necessary treatment, increasing the risk of adverse health outcomes for both maternal health and fetal development. Summary: Preconception care aims to address these concerns by providing guidance to mitigate factors that may negatively impact maternal and fetal health. This includes optimizing behavioral, personal, and environmental determinants of health. In this review article, we discuss the role of preconception care in supporting an optimized pregnancy, safe delivery, and healthy postpartum period for the patients wishing to have babies. Key Messages: Proper preconception counseling can improve the pregnancy outcomes. Healthcare professionals play a crucial role in preconception care by providing patients with accurate medical knowledge and guidance, enabling them to make informed decisions and ensuring a safe and well-prepared pregnancy and childbirth.

Background: Eosinophils and eosinophil infiltration are the hallmark for the diagnosis of eosinophilic esophagitis (EoE), which represents the most common cause of solid food dysphagia in young adults. However, the role of eosinophils in the pathogenesis of EoE has been increasingly questioned. Summary: It is now well accepted that EoE is a Th2-mediated disorder with a myriad of inflammatory processes being involved rather than a single cell disease. In recent years, several nuances of EoE, so-called EoE variants, have been described, among which are EoE-like esophagitis, nonspecific esophagitis, lymphocytic esophagitis, and potentially also mast-cell esophagitis. These variants appear to have distinct molecular fingerprints sharing pronounced traits of EoE. Of note, there is a considerable flux between the variants (with frequent transitions) and eventual progression to EoE over time. Thus, EoE variants and EoE appear to be a spectrum disorder, where EoE only represents the most extreme phenotype. Key Messages: This review summarizes current knowledge about these different variants and discusses future directions and open questions.

Introduction: No real-world studies have compared efficacy of ustekinumab (UST) and risankizumab (RZB) for the treatment of Crohn’s disease (CD). Methods: We retrospectively collected the data of patients with CD treated with UST or RZB between May 2017 and March 2024 at the Institute of Science Tokyo and analyzed clinical remission rate at weeks 8 and 28 using Harvey-Bradshaw Index (HBI), with remission defined as a HBI ≤4. Result: A total of 111 patients who were treated with UST and 29 patients treated with RZB were included in the analysis. RZB had higher efficacy both at weeks 8 (82.8% vs. 62.2%, p = 0.0465) and 28 (79.3% vs. 56.8%, p = 0.0321) than UST in the full study cohort, and at weeks 8 (55.6% vs. 18.4%, p = 0.0352) and 28 (66.7% vs. 18.4%, p = 0.0083) in the patients with clinically active disease and anti-TNFα exposed patients. During the observation period, 1 patient with RZB (3.45%) experienced an adverse event that required hospitalization, and 1 patient in the UST group (0.900%) experienced an adverse event that led to treatment discontinuation. Conclusion: RZB may offer greater short-term efficacy than UST, with an acceptable safety profile in real-world settings.