Inflammatory Intestinal Diseases最新文献

Introduction: Upadacitinib and tofacitinib, oral Janus kinase inhibitors, have demonstrated efficacy and safety in ulcerative colitis (UC) in clinical trials. However, real-world comparative data are limited. We conducted a systematic review and meta-analysis of studies directly comparing upadacitinib to tofacitinib in UC management.

Methods: We conducted a systematic search of multiple databases through August 2025 for studies comparing upadacitinib and tofacitinib for UC management. The primary outcome was steroid-free clinical remission (SFCR) at weeks 8-14. Secondary outcomes included SFCR at later timepoints, clinical and endoscopic remission, biochemical remission, treatment discontinuation, colectomy, and safety. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random effects model. Heterogeneity was assessed using the I ²% statistic.

Results: Ten retrospective studies with 2,021 patients (879 upadacitinib and 1,142 tofacitinib) were analyzed. Upadacitinib was associated with significantly higher SFCR at weeks 8-14 (OR 1.98; 95% CI: 1.32-3.97; I ² = 30%), 48-60 weeks (OR 2.32; 95% CI: 1.50-3.58; I ² = 0%), and at the end of study follow-up (OR 3.60; 95% CI: 1.73-3.92; I ² = 0%). Rates of endoscopic and biochemical remission did not differ significantly. Treatment discontinuation was less frequent with upadacitinib (OR 0.51; 95% CI: 0.34-0.77; I ² = 22%). Overall safety was comparable, except for higher odds of acne with upadacitinib (OR 4.30; 95% CI: 1.86-9.95; I ² = 0%).

Conclusion: Upadacitinib may be more effective than tofacitinib in achieving and sustaining SFCR, with better treatment persistence and similar overall safety. Larger, prospective head-to-head trials are needed to validate these findings.

Introduction: Ulcerative colitis (UC) is a diffuse, nonspecific inflammatory disease of unknown etiology. Although corticosteroids are essential for inducing remission in moderate to severe UC, steroid dependence and refractoriness remain significant clinical obstacles. Predicting which patients will develop steroid dependence or refractoriness remains challenging. Furthermore, difficult-to-treat (D-to-T) cases - those unresponsive to advanced therapies - have emerged as additional therapeutic concerns. This study aimed to identify factors associated with refractory UC, including steroid-dependent, steroid-refractory, and D-to-T presentations.

Methods: A total of 216 patients with UC who received treatment at Sapporo Medical University Hospital between April 2017 and December 2023 were retrospectively analyzed. Patients were classified into four groups: steroid-naive (SN), steroid-free (SF), steroid-dependent (SD), and steroid-refractory (SR). D-to-T cases were identified within the SD and SR groups. Patient background characteristics were obtained from electronic medical records. Variables analyzed included sex, age of onset, disease duration, alcohol consumption, smoking status, disease phenotype, extraintestinal manifestations (EIMs), and cytomegalovirus (CMV) and Clostridioides difficile infection status.

Results: Significant differences were observed in the prevalence of EIM and CMV reactivation across the four groups (p < 0.001 for EIM; p < 0.001 for CMV). The prevalence of EIM was significantly higher in the SR group compared with the SN group (45.5% vs. 7.7%, p = 0.002) and the SF group (45.5% vs. 4.5%, p < 0.001). CMV reactivation was more frequent in the SR group than in the SN group (36.4% vs. 1.3%, p < 0.001) and the SF group (36.4% vs. 4.5%, p < 0.004). Multivariable analysis revealed that, in comparison with the SN group, the SD group was independently associated with EIM (odds ratio [OR] = 4.59, 95% confidence interval [CI]: 1.35-15.6) and CMV reactivation (OR = 12.5, 95% CI: 1.31-119). Compared to the SF group, the SD group was associated with EIM (OR = 5.71, 95% CI: 1.44-22.7). The SR group was independently associated with EIM (OR = 12.8, 95% CI: 2.51-64.9) and CMV reactivation (OR = 65.1, 95% CI: 4.39-964) compared to the SN group. Compared to the SF group, the SR group was associated with EIM (OR = 16.4, 95% CI: 2.95-90.8) and CMV reactivation (OR = 17.0, 95% CI: 2.03-142). There are also significant associations between D-to-T status and both EIM (p < 0.01) and CMV reactivation (p = 0.037).

Conclusions: Among patients with UC, the presence of EIM and CMV reactivation was significantly associated with steroid dependence, steroid refractoriness, and resistance to biologic and molecular-targeted therapies.

Introduction: Vedolizumab (VDZ) has been available for Japanese patients with ulcerative colitis (UC). However, real-world data regarding the long-term efficacy and safety of VDZ in Japanese patients with active UC remain limited. This study aimed to evaluate the long-term outcomes of VDZ and identify prognostic factors in Japanese patients with UC.

Methods: This retrospective multicenter cohort study was conducted at six hospitals and one clinic in Hokkaido, Japan. A total of 172 patients with UC who received VDZ treatment between November 2018 and October 2022 were included. Treatment persistence rates at 52, 104, and 156 weeks were evaluated. The median follow-up duration was 51 weeks (range: 1-156). Clinical response, clinical remission, and mucosal healing rates were assessed at weeks 6 and 52. Prognostic factors for treatment response were analyzed using univariate and multivariate logistic regression analyses.

Results: The cumulative treatment persistence rates at weeks 52, 104, and 156 were 68.1%, 58.1%, and 50.7%, with 64, 32, and 17 patients remaining on VDZ at those respective weeks. Clinical response and remission rates at week 6 were 63.3% and 52.3%, while clinical remission, corticosteroid-free remission, and mucosal healing rates at week 52 were 59.3%, 53.9%, and 52.3%, respectively. Multivariable analysis identified male sex and absence of prior anti-tumor necrosis factor (TNF) exposure as factors associated with clinical response at week 6 (odds ratio [OR] 2.17, p = 0.045; OR 2.26, p = 0.046). Clinical response at week 6 was strongly associated with clinical remission at week 52 (OR 14.5, p < 0.01). Among patients previously treated with anti-TNF agents, those with secondary loss of response had significantly higher remission rates at week 52 than did those with primary non-response (p < 0.01). Adverse events were observed in 6 patients, with one case leading to treatment discontinuation; no severe adverse events were reported.

Conclusions: VDZ demonstrated favorable long-term treatment persistence, efficacy, and safety in Japanese patients with UC. The efficacy of VDZ may vary depending on prior anti-TNF therapy outcomes, particularly the reasons for discontinuation. These findings provide valuable insights for optimizing treatment strategies in UC patients, although further prospective studies are warranted.

Introduction: Ustekinumab (UST) is increasingly used in Crohn's disease patients with prior tumor necrosis factor-α inhibitor (TNFi) failure. However, whether to switch to another biologic or continue TNFi therapy at the time of surgery remains an important unresolved clinical question.

Methods: Among patients who underwent intestinal resection during TNFi therapy at our hospital from January 2008 to February 2022, 39 patients continued TNFi after surgery (TNFi continuation group) and 15 patients switched to UST after surgery (UST switch group) were included. Clinical and endoscopic recurrence rates were compared over long-term follow-up.

Results: This retrospective cohort study showed that the cumulative 2-year clinical recurrence-free rate was 82.6% in the TNFi continuation group and 60.0% in the UST switch group, with no statistical difference in the cumulative clinical recurrence-free rate between the two groups (log-rank test; p = 0.863). The follow-up endoscopy showed that postoperative endoscopic recurrence (PER) was observed in 14 of 34 patients (38.2%) in the TNFi group and 8 of 14 patients (57.1%) in the UST switch group, with no statistical difference between the two groups (p = 0.3384). Absence of PER at follow-up correlated with better long-term clinical outcomes. A medical claims database analysis confirmed no significant difference in the cumulative clinical recurrence-free rate (p = 0.232) or subsequent intestinal surgery-free rate (p = 0.554) between the TNFi continuation group and the UST switch group.

Conclusion: In patients undergoing surgery during TNFi treatment, there was no statistically significant difference between postoperative UST switching and TNFi continuation.

Introduction: Vedolizumab (VDZ) is a gut-selective integrin antagonist approved for the treatment of ulcerative colitis. While its efficacy and safety have been demonstrated in clinical trials, real-world data on long-term treatment persistence and factors associated with loss of response are limited.

Methods: We conducted a retrospective single-center observational study to evaluate the persistence of treatment and factors influencing loss of response in 59 patients with ulcerative colitis treated using VDZ. Clinical outcomes, endoscopic findings, and the impact of concomitant immunomodulator or 5-aminosalicylic acid use were analyzed.

Results: Thirty-two patients (54.2%) had achieved clinical remission at week 24 and 27 (45.8%) had not. The cumulative VDZ persistence rate at 3 years was 39.7%. Patients who had achieved endoscopic improvement at 24 weeks exhibited a significantly higher persistence rate. The incidence of adverse events was low (1.7%). The impact of immunomodulator and 5-aminosalicylic acid co-administration on treatment persistence was minimal.

Conclusion: Endoscopic improvement at week 24 was a key predictor of long-term VDZ persistence.

Introduction: Inflammatory bowel disease (IBD) burdens patients and healthcare systems, often due to frequent emergency department (ED) visits. Comprehensive programs that connect members to providers with disease-specific expertise may improve IBD management and reduce emergency care needs.

Methods: This study evaluates the impact of a virtual condition management program on ED utilization among commercially insured members with IBD using claims data from 2017 to 2024. Propensity scores were estimated, with inverse probability of treatment weighting applied to balance baseline covariates (i.e., age, sex, prior healthcare utilization, and Charlson Comorbidity Index [CCI] scores). Weighted negative binomial regression estimated the association between program engagement and ED visit frequency, controlling for baseline characteristics. Sensitivity analyses using weighted logistic regressions evaluated the likelihood of any, gastrointestinal (GI)-related, and non-emergent ED visits post-eligibility.

Results: Engagement was significantly associated with reduced ED utilization. Members who chose to engage experienced a 45.7% reduction in ED visits, on average, compared to unengaged (p = 0.007). Males had significantly lower visits (p = 0.012), higher CCI scores were associated with fewer visits (p = 0.005), and prior ED use was strongly associated with visit frequency (p < 0.001). Sensitivity analyses reinforced these findings as engaged members had significantly lower odds of any (odds ratio [OR]: 0.50; p = 0.003), GI-related (OR: 0.46; p = 0.014), and non-emergent (OR: 0.41; p = 0.722) visits.

Conclusions: Engagement with a care management program was associated with reduced ED visitation and lower likelihoods of any, non-emergent, and GI-related visits. Virtual programs offering condition-specific expertise may improve disease management and decrease reliance on ED services for patients with chronic GI diseases.

Background: Fecal microbiota transplantation (FMT) is an emerging therapeutic strategy for inflammatory bowel disease (IBD). Every step of the FMT process, from donor recruitment and patient selection to pretreatment protocols, administration techniques, and post-FMT interventions, can significantly influence treatment outcomes. These components are interrelated, and even subtle differences in methodology may affect the overall efficacy of FMT for IBD. This review aimed to outline the current clinical experience and findings regarding FMT for IBD during the application process.

Summary: Donor screening has traditionally focused on safety. In recent years, although safety remains essential, increasing attention has been paid to the donor selection efficacy. Particularly, identifying patients who are most likely to benefit from FMT is crucial because timely and appropriate patient selection can prevent delays in effective treatment. Pretreatment strategies and FMT procedures remain hot topics of current research. Approaches, such as antibiotic pretreatment, may enhance microbial engraftment; however, the optimal antibiotic combination remains unclear. Bowel lavage is commonly used to reduce the microbial burden and facilitate donor microbiota colonization, whereas corticosteroid pretreatment has shown conflicting results. There are various routes of administration, and oral capsules are gaining popularity owing to their safety and patient acceptability. Stool preparation factors, including the use of single versus pooled donors, anaerobic processing, and storage form (fresh, frozen, or freeze-dried), can significantly influence microbial viability and clinical outcomes. Repeated FMTs tend to be more effective than single infusions; nonetheless, the optimal frequency remains unclear. Post-FMT interventions, such as dietary modifications and supplementation with prebiotics, such as pectin and alginic acid, are also promising strategies.

Key messages: Despite encouraging results, variations in treatment protocols, donor characteristics, and host factors continue to obscure the definitive predictors of FMT success. Further randomized controlled trials and mechanistic studies are required to standardize these procedures and optimize their long-term efficacy.

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

[This corrects the article DOI: 10.1159/000547076.].

Introduction: Up to 85% of pediatric patients affected by Crohn's disease experience growth failure. This study aims to elucidate the effects of anti-tumor necrosis factor (TNF) biologics on patient growth.

Methods: This retrospective analysis examined height, height velocity and weight in pediatric patients with Crohn's disease from the Swiss Inflammatory Bowel Disease Cohort Study between 2007 and 2020 (n = 97). Z-scores were determined according to age and gender of a healthy pediatric population. Growth of patients treated with anti-TNF biologics and immunomodulators was analyzed by linear regression over 5 years and compared within each subgroup by paired Student t tests 1 year (T1), 2 years (T2), and 5 years (T5) after treatment initiation.

Results: Mean height and weight z-scores at diagnosis were -0.3 ± 1.3 and -1.0 ± 1.6, respectively (age at diagnosis 11.1 ± 2.7 years, 52.0% male). Initial treatment was led by azathioprine (58.3%) and infliximab (19.8%). Patients treated with biologics exhibited significant height increase at T1 (p = 0.022), with an overall flat height evolution (y = 0.00x - 0.31), whereas significant weight increase was maintained at T5 (p = 0.0005, y = 0.13x - 0.50). Patients on immunomodulators showed a height increase (y = 0.15x - 0.20) and a significant weight increase at T2 (p = 0.0047, y = 0.10x - 0.41). Height velocity z-scores showed a significant increase across both genders. Factors contributing to a decreased height z-score included male sex, age 10 and below at diagnosis, a concomitant corticosteroid treatment and a top-down treatment strategy.

Conclusion: Our findings indicate that anti-TNF biologics are associated with significant short-term height and long-term weight gains in pediatric patients with Crohn's disease, similar to those observed with immunomodulators.