Introduction: E6011 is a newly developed humanized monoclonal antibody that binds to and neutralizes fractalkine with high specificity and affinity. In a previous phase 1, open-label study, E6011 demonstrated good tolerability and preliminary efficacy in Japanese patients with mild to moderate active Crohn’s disease (CD). Methods: In this early phase 2, double-blind, placebo-controlled study, we examined the efficacy and safety of E6011 in patients with moderate to severe active CD in a 12-week, double-blind period and the long-term efficacy and safety of E6011 in a subsequent open-label period for a maximum of 52 weeks. The primary efficacy endpoint was the percentage of patients who achieved a decrease in the CD activity index (CDAI) by ≥100 points from baseline at week 12. Results: Of the planned 40 participants, enrollment was closed after 25 had been enrolled, primarily because of the delay in patient enrollment during the COVID-19 pandemic. A decrease in CDAI by ≥100 points was achieved in 33.3% (4/12) in the E6011 group and 23.1% (3/13) in the placebo group at week 12, resulting in a posterior difference of 9.6% (95% credible interval −23.7% to 42.7%). The probability of the difference between groups being ≥25% was 18.3%, which did not exceed the prespecified threshold of 50%. E6011 was safe and well tolerated in the 12-week, double-blind period. No new safety issues were reported in patients treated until week 40. Conclusion: E6011 was safe and well tolerated in patients with moderate to severe active CD. Owing to the small sample size in this study, further studies are necessary to accurately evaluate its efficacy.

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.

Introduction: Budesonide, with its high topical steroidal activity, effectively prevents strictures following esophageal endoscopic treatment. However, its effectiveness in preventing restenosis after endoscopic balloon dilation (EBD) in patients with Crohn’s disease (CD) remains unclear. We aimed to evaluate the safety and effectiveness of oral budesonide after EBD in patients with CD. Methods: We conducted a multicenter prospective study of patients with CD who underwent EBD at the University of Osaka and its affiliated hospitals between March 2018 and March 2023 (UMIN000031839, jRCT1051190043). Oral budesonide was administered for 4 weeks after EBD, and patients were followed up for 52 weeks. Safety and effectiveness within 12 and 52 weeks of the procedure were evaluated, with endoscopic evaluation of restenosis at week 52. The stenosis diameter and length were estimated endoscopically and radiographically, respectively. In the historical control study, consecutive patients with CD who underwent EBD between February 2016 and July 2018 were included. The incidence rates of obstructive symptoms and hospitalization at 52 weeks after EBD were retrospectively investigated from the medical records. Results: Overall, 15 patients were analyzed (male, 14 [93.3%]; median age, 44 years [37–49]; disease type, L1, 8 [53.3%]/L3, 7 [46.7%]; stenosis location, jejunum, 1 [6.7%]/ileum, 8 [53.3%]/ileocolonic, 6 [40.0%]; median stenosis diameter, 5 mm [5–6]). No serious complications were observed within 12 or 52 weeks. Twelve (80%) patients showed no symptoms of stenosis within 52 weeks. Of the 14 patients who underwent an endoscopy at week 52, re-EBD was not required in 3 patients (21.4%). The stenosis diameter at week 52 improved significantly compared to the pre-dilation measurements (p = 0.004). Furthermore, the 15 patients treated with budesonide had a significantly lower incidence rates of obstructive symptoms and hospitalization compared to the 19 historical control patients (p = 0.020 and 0.035, respectively). Conclusion: Budesonide administration after EBD can be safely performed in patients with CD and may be effective in preventing restenosis and avoiding hospitalization and intestinal surgery.

Introduction: Patients with inflammatory bowel disease (IBD) have chronic inflammation of the gastrointestinal tract, which confers a higher risk of developing venous thromboembolism (VTE) compared to individuals without IBD. Current guidelines advocate routine VTE prophylaxis for hospitalized IBD patients, but utilization remains inconsistent. This study evaluates the incidence of VTE in hospitalized IBD patients by severity of illness (SOI) to generate real-world evidence that may guide adherence to prophylaxis guidelines and inform future risk-based prevention protocols. Methods: We utilized data from the 2020 National Inpatient Sample (NIS) database, the largest inpatient care database in the USA. All patients aged ≥18 years with primary diagnosis of IBD, identified by ICD-10 codes, were included. SOI was defined using the All Patient Refined Diagnosis Group (APR-DRG) SOI: minor, moderate, major, and extreme. VTE was identified by the ICD-10 codes for deep vein thrombosis (DVT) and pulmonary embolism (PE). Baseline demographics of study participants were obtained. The primary outcome studied was the incidence of VTE graded by disease severity. Logistic regression analysis was used to calculate odds of VTE in study participants based on SOI adjusted for baseline characteristics. Sampling weights were applied to generate nationally representative estimates. Results: A total of 252,485 patients met criteria and were included. The incidence of VTE increased with increasing SOI. The incidence of VTE in patients with minor SOI was low at 0.4% compared to 7.6% in patients with extreme SOI. The incidence of DVT and PE showed similar trends across SOI. The adjusted odds ratios of VTE in patients admitted with moderate, major, and extreme SOI were 2.9 (95% confidence interval [CI]: 2.1–3.9), 10.2 (95% CI: 7.4–13.9), and 20.8 (95% CI: 14.8–29.8) compared to that of patients admitted with minor SOI. Conclusion: Our findings demonstrate a clear relationship between illness severity and VTE risk, reinforcing current guidelines that recommend thromboprophylaxis for all hospitalized IBD patients. Ensuring consistent implementation, especially in patients with severe illness, is essential to preventing avoidable complications.

Introduction: Interleukin (IL)-12/23 and IL-23 inhibitors have emerged as promising therapeutic options for moderate-to-severe Crohn’s disease (CD), but comparative data between agents remain limited. This study aimed to assess and rank the efficacy of IL-12/23 and IL-23 inhibitors across key clinical and endoscopic outcomes using network meta-analysis. Methods: We included randomized controlled trials (RCTs) evaluating IL-12/23 (ustekinumab) and IL-23 inhibitors (risankizumab, mirikizumab, guselkumab, briakinumab, and MEDI2070) versus placebo or each other in adult patients with moderate-to-severe CD. Primary outcomes included clinical and endoscopic remission (assessed at the end of the induction and maintenance phases) and corticosteroid-free clinical remission (assessed at the end of the maintenance phase). Risk ratios (RRs) were estimated using a random-effects model. All analyses were conducted in R using the netmeta package. Surface under the cumulative ranking curve (SUCRA) analysis was used to rank treatments across these endpoints. Results: Fourteen RCTs involving 4,464 patients during the induction phase and 2,601 patients during the maintenance phase were included. Guselkumab achieved the highest clinical remission rate compared to placebo at the end of both the induction phase (RR = 2.62; 95% confidence interval [CI], 2.03–3.39; SUCRA: 91%) and the maintenance phase (RR = 2.37; 95% CI, 1.64–3.42; SUCRA: 85%). In addition, guselkumab was superior to mirikizumab in terms of clinical remission at the end of the induction phase (RR = 1.66; 95% CI, 1.16–2.37). Guselkumab was also the most effective agent for achieving corticosteroid-free clinical remission compared to placebo (RR = 3.06; 95% CI, 1.52–6.16; SUCRA: 78%) at the end of the maintenance phase. Mirikizumab achieved the highest endoscopic remission rate compared to placebo at the end of both the induction phase (RR = 3.52; 95% CI, 1.50–8.27; SUCRA: 78%) and the maintenance phase (RR = 5.84; 95% CI, 2.76–12.37; SUCRA: 88%). Furthermore, mirikizumab, guselkumab, and risankizumab were superior to ustekinumab in terms of endoscopic remission at the end of the maintenance phase. Conclusions: These findings suggest that guselkumab may be a potential first-line therapy for patients presenting with predominant clinical symptoms, offering the additional benefit of reducing corticosteroid use and its associated long-term risks. Conversely, mirikizumab may be the preferred option for patients with persistent mucosal inflammation, owing to its superior efficacy in achieving endoscopic remission.

Background: Mucosal healing is necessary to maintain the long-term remission of ulcerative colitis (UC). Currently, the gold standard for assessing mucosal healing is endoscopic diagnosis. The Mayo Endoscopic Subscore (MES) is the most commonly used index for evaluating endoscopic mucosal healing; however, a certain number of patients may experience relapse during the clinical course of the disease, even at MES 0, where the mucosa appears to be in a state of healing. Therefore, the usefulness of image-enhanced endoscopy, such as narrow-band imaging, linked color imaging, autofluorescence imaging, red dichromatic imaging, texture and color enhancement imaging, and i-Scan, has been increasingly reported in recent years for the diagnosis of complete mucosal healing without recurrence. The importance of histological healing has also been emphasized in recent years. The three main histological scoring systems currently used are the Geboes score, Nancy Histological Index, and Robarts Histologic Index. When combined with MES, these histological assessments have been reported to considerably predict UC relapse. However, the relevance of diagnosing histological activity in patients with MES 0 and endoscopically confirmed mucosal healing remains debatable. Cytokines play an important role in UC pathogenesis, as evidenced by the effectiveness of biologics and small molecules that target specific cytokines in treating refractory cases. Therefore, the concept of “molecular healing” has recently been proposed to describe the regulation of cytokine profiles during mucosal healing in patients with UC. Summary: Specific mucosal cytokine expression correlates with endoscopic severity, predicts UC relapse, and indicates the therapeutic efficacy of biologics. This highlights the growing interest in understanding UC pathogenesis based on cytokine expression. Defining mucosal healing in UC based on mucosal cytokine expression is expected to evolve as a next-generation diagnostic approach. Key Messages: Therefore, accurate diagnosis of mucosal healing in patients with UC is essential. In this review, we describe mucosal healing from the perspective of mucosal gene expression, which has recently gained attention alongside advances in conventional endoscopic and histological diagnostics.

Introduction: There are a limited number of studies that have investigated mesalazine persistence and adherence using administrative/pharmacy claims data that may approximate real-world clinical practice data; therefore, the aim of this study was to compare the adherence to oral mesalazine between different groups of inflammatory bowel disease (IBD) patients in relation to the tablet strength (number of pills per day) dispensed in retail pharmacy. Methods: This was a retrospective cohort study in French patients using the IQVIA Longitudinal Prescription Data, a patient database based on retail pharmacy claims. Results: Of the 21,669 patients with a pharmacy claim for oral mesalazine initiated for IBD between June 2020 and April 2022, after exclusion criteria were applied, 12,122 IBD treatment-naïve patients initiating mesalazine treatment were included. A high-strength (HS) (1,600 mg), medium-strength (MS) (800–1,000 mg), and low-strength (LS) (400–500 mg) mesalazine tablet was dispensed to 1,216, 8,631, and 2,275 patients, respectively. Persistence to medication at 6 months of follow-up was 44.6%, 35.4%, and 25.3% in the HS, MS, and LS group, respectively. After 1 year of follow-up, it was 22.0%, 17.1%, and 11.5% in the HS, MS, and LS groups, respectively. Patient adherence to mesalazine tablets was 41.3% patients in the HS group, 35.5% patients in the MS group, and 28.0% patients in the LS group (p < 0.001). Conclusion: The results showed a consistent higher adherence with the decrease of pill burden. HS tablets were significantly associated with higher persistence and higher adherence to medication compared to the MS and LS tablet group.

Introduction: Biologics and Janus kinase inhibitors have emerged as treatment options for inflammatory bowel disease (IBD); however, Japanese guidelines do not specify priorities for the use of these therapies. Therefore, shared decision-making (SDM) is important for their selection. This study aimed to survey patients with IBD who received SDM from pharmacists regarding their satisfaction and willingness to pay (WTP). Methods: A cross-sectional survey was conducted between January 2020 and June 2024. Patients who visited the IBD Outpatient Clinic at Kameda Clinic and received SDM during this period were surveyed. Patient satisfaction was assessed using the visual analog scale (0–100). WTP was surveyed with four options: JPY 0, JPY 250 (approximately USD 2.5), JPY 500 (approximately USD 5), and over JPY 500. Results: A total of 26 patients completed the questionnaire. The median satisfaction score for SDM was 96 (interquartile range: 90–100). Twenty patients (76.9%) indicated WTP for SDM. Eight patients (30.8%) chose JPY 250, 10 patients (38.5%) chose JPY 500, and 2 patients (7.7%) indicated over JPY 500. Conclusion: This pilot study is the first to demonstrate that SDM by pharmacists is highly satisfactory for patients with IBD. Furthermore, many patients expressed a WTP for SDM as part of counseling. These findings support the involvement of pharmacists, alongside physicians, in the SDM process for IBD treatment.

Background: Eosinophilic esophagitis (EoE) is a chronic inflammatory immune-mediated disease characterized by eosinophilic esophageal inflammation, leading to remodeling, fibrosis, and stricture formation. Esophageal dilation is one of the treatment modalities of dysphagia in fibrostenotic EoE, though it does not address the underlying inflammatory process. The development of biological therapies has raised questions about the ongoing need for mechanical dilation. Summary: Esophageal dilation remains an effective and safe procedure for relieving dysphagia in EoE patients with fibrostenotic changes. New diagnostic modalities like functional lumen imaging probe (FLIP) increase the diagnostic yield of esophageal strictures while evaluating the biomechanical properties of the esophageal wall. Esophageal stricture dilation provides symptoms relief in EoE but has no effect on the inflammation and hence does not prevent disease progression. Recent studies suggest that biological therapies may reverse both the inflammation and the fibrotic remodeling in some patients, potentially reducing the need for dilation. However, in cases of severe fibrosis or narrow-caliber esophagus, dilation remains a cornerstone in the management of EoE. Key Messages: Esophageal dilation is effective for symptomatic improvement in EoE patients with strictures but does not reduce esophageal inflammation. Diagnostic tools like FLIP improve esophageal strictures detection and dilation tailoring. Biologic therapies show promise in targeting esophageal inflammation and fibrosis, but long-term data are needed. Dilation will remain essential for treating the fibrostenotic phenotype of EoE.