Inflammatory Intestinal Diseases最新文献

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.

Background: Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a rare hereditary disorder characterized by multiple small intestinal ulcers, chronic anemia, and hypoproteinemia. Initially reported by Okabe et al. [J Jpn Soc Gastroenterol. 1968;65:1114-7] in 1968 as chronic nonspecific multiple ulcers of the small intestine, the condition was later identified as a genetic disorder caused by mutations in the SLCO2A1 gene, which encodes a prostaglandin (PG) transporter. Unlike typical autosomal recessive disorders, CEAS predominantly affects females and is frequently present with extraintestinal manifestations such as digital clubbing, pachydermia, and periostosis.

Summary: This review provides a comprehensive summary of the epidemiology, pathogenesis, clinical features, diagnostic criteria, and management of CEAS, with an emphasis on newly established diagnostic protocols in Japan. CEAS is characterized by multiple shallow circumferential or oblique ulcers in the small intestine, often resembling NSAID-induced enteropathy. Laboratory findings typically include iron deficiency anemia and hypoproteinemia, while urinary PG metabolite levels are significantly elevated. Genetic testing for SLCO2A1 mutations, particularly the c.940 + 1G>A splice site mutation, confirms the diagnosis. While symptomatic management with enteral nutrition, iron supplementation, blood transfusions, and albumin infusion is the mainstay of therapy, definitive treatments remain unavailable. Endoscopic balloon dilation may be useful in cases of intestinal strictures, but surgical intervention is frequently required.

Key messages: (i) CEAS should be considered in cases of chronic iron deficiency anemia and hypoproteinemia with unexplained small intestinal ulcers. (ii) Genetic testing for SLCO2A1 mutations, combined with assessment of small intestinal morphology, is essential for accurate diagnosis. (iii) Current treatment options are limited to symptomatic management and surgical intervention, highlighting the need for further research to develop effective therapies.

Introduction: It remains unclear whether Janus kinase (JAK) inhibitors differ in efficacy and safety between elderly and non-elderly patients with ulcerative colitis.

Methods: We retrospectively compared outcomes between patients who started a JAK inhibitor at ≥65 years (elderly group) and those <65 years (non-elderly group).

Results: Among 228, 215, and 159 patients treated with upadacitinib, filgotinib, and tofacitinib, we identified 14, 36, and 13 elderly patients, respectively. There were no significant differences in efficacy between elderly and non-elderly patients for any of the three JAK inhibitors. The elderly group had a 3-fold higher risk of herpes zoster infection with upadacitinib or tofacitinib compared to the non-elderly group, whereas the risk with filgotinib was less than 3% in both groups. The non-elderly group had a 3-fold higher risk of acne with upadacitinib.

Conclusion: Adverse event risks with JAK inhibitors should be considered by age. Given the limitations of this study, including its retrospective design and small sample size, further studies with larger sample sizes are needed to validate our findings.

Introduction: Crohn's disease (CD) is a chronic inflammatory condition of the digestive tract, characterized by a noncontinuous pattern of transmural inflammation, leading to a significant decline in quality of life and productivity. For biologic-naïve patients, anti-tumor necrosis factor (TNF)-α and anti-interleukin (IL)-12/23 therapies are commonly recommended. This study compares anti-IL-12/23 and anti-TNF-α for clinical remission, corticosteroid-free remission, endoscopic remission, and endoscopic response in biologic-naïve patients.

Methods: We searched PubMed, Google Scholar, VHL, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov for randomized clinical trials and cohort studies. Data were analyzed using odds ratios (ORs) with 95% confidence intervals (CIs). A random-effects model was applied for meta-analysis.

Results: Only 6 out of 5,401 articles were included, involving a total of 1,103 patients. Of these, 636 (57.6%) received anti-TNF-α therapy (infliximab or adalimumab), while 467 (42.4%) received anti-IL-12/23 (ustekinumab) therapy. Within 52 weeks, there were no statistically significant differences found between Ustekinumab and anti-TNF-α in terms of clinical remission (OR: 0.92, 95% CI: 0.55-1.54, p = 0.75), endoscopic remission (OR = 0.583, 95% CI: 0.289-1.176; p = 0.13), corticosteroid-free remission (OR: 1.19, 95% CI: 0.87-1.64, p = 0.28), or endoscopic response (OR = 0.48, 95% CI: 0.147-1.578; p = 0.23).

Conclusion: This meta-analysis found no significant differences in clinical remission, corticosteroid-free remission, endoscopic remission, or endoscopic response within 52 weeks between ustekinumab and anti-TNF-α agents in biologic-naïve CD patients. However, due to study limitations, further high-quality, head-to-head trials are needed to refine treatment selection and optimize outcomes.

Background: Ciclosporin and infliximab have equal short-term efficacy in treating acute severe ulcerative colitis (ASUC). However, data about long-term outcome and switching to a second rescue therapy are limited.

Methods: Patients with steroid-refractory ASUC treated at a tertiary center in Switzerland were retrospectively analyzed regarding the outcome of different rescue therapies. Colectomy-free survival rates at 1, 3, and 5 years were estimated through Kaplan-Meier method. Furthermore, predictors of colectomy, the presence of adverse events at 1 year and mortality during the entire follow-up were assessed.

Results: We analyzed a total of 46 patients who were treated initially with either ciclosporin (n = 31) or infliximab (n = 15) due to steroid-refractory ASUC between January 2010 and July 2021. A total of 13% patients received a second rescue therapy. In sum, 78%, 67%, and 48% were colectomy-free at 1, 3, and 5 years, respectively. Although there was a significant difference between the three arms in colectomy-free survival (p = 0.026), a post hoc analysis could not demonstrate a difference between each individual therapy compared to another. The post hoc analysis indicated a nonsignificant benefit with sequential therapy in comparison to ciclosporin (CsA) regarding the colectomy-free survival (p = 0.087). The outcome between infliximab and CsA was not statistically different (p = 0.149). The number of previous advanced therapies was negatively associated with 1-year colectomy-free survival (p = 0.049). Other variables such as age at hospitalization, sex, dose of steroids, disease duration, and albumin did not correlate with a higher risk of 1-year colectomy.

Conclusions: This real-world single-center analysis confirms the equal efficacy and safety of infliximab and ciclosporin over a follow-up of 5 years. Patients not responding to the first may benefit of a second rescue therapy without increasing the risk of complication or mortality.

[This corrects the article DOI: 10.1159/000545081.].