Inflammatory Intestinal Diseases最新文献

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.

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.

Introduction: Upadacitinib (UPA), a Janus kinase inhibitor approved for the treatment of Crohn's disease (CD), has demonstrated high efficacy in clinical trials; however, real-world data on its outcomes remain limited. This study evaluated UPA outcomes in patients with CD in a real-world setting.

Methods: We retrospectively analyzed patients who initiated UPA treatment between June 2023 and June 2024. The primary endpoints were clinical response and remission at 12 and 54 weeks. The secondary endpoints included changes in the C-reactive protein (CRP) levels, serum albumin levels, and perianal fistula response.

Results: Thirteen patients (mean age, 32.0 years; 92.3% male; mean disease duration, 114.1 months) were included. At baseline, three (23.1%) patients used oral corticosteroids, and 11 (84.6%) had undergone prior biologic therapy, with nine (81.8%) exposed to anti-tumor necrosis factor-alpha antibodies. The mean follow-up period was 53.1 weeks, and the 54-week continuation rate was 83.3%. The clinical response rates were 46.2% and 53.8%, and the remission rates were 69.2% and 84.6% at 12 and 54 weeks, respectively. The mean Crohn's Disease Activity Index scores decreased from 226.8 at baseline to 73.7 at 54 weeks, and the average CRP and albumin levels improved correspondingly. Among the 7 patients (53.8%) with draining perianal fistulas, six (85.7%) achieved cessation of pus discharge by week 8 (mean, 4.4 weeks). No significant adverse events were observed.

Conclusion: UPA appears to be an effective treatment for CD and may facilitate the early resolution of perianal fistulas, supporting its role in managing perianal disease.

Introduction: De novo inflammatory bowel disease (IBD) is a rare but clinically significant complication after solid organ transplantation (SOT), with incidence higher than that in the general population. Its pathogenesis, diagnostic challenges, and optimal management remain poorly defined. We describe 6 cases of de novo IBD following liver or heart transplantation and evaluate therapeutic outcomes with selective biologics targeting the IL-23 pathway.

Methods: Six SOT recipients (3 liver, 3 heart) developed new-onset ulcerative colitis-type (UC-type, n = 3) or Crohn's disease-like (CD-like, n = 3) IBD after a median of 47.5 months post-transplantation. None had pre-transplant intestinal symptoms; colonoscopy was negative before transplantation in 2 UC-type cases. Alternative etiologies - including cytomegalovirus colitis, drug-induced colitis, and post-transplant lymphoproliferative disorder - were rigorously excluded. Treatments included systemic corticosteroids, mirikizumab, ustekinumab, or risankizumab. Median follow-up was 15.6 months.

Results: Corticosteroids induced remission in 2 UC-type cases, while one steroid-refractory UC-type case and all CD-like cases achieved clinical improvement and endoscopic response or remission with IL-23-targeted biologics. No opportunistic infections, severe biologic-related adverse events, or graft rejection were observed.

Conclusions: De novo IBD emerged years after SOT, with variable phenotypes despite baseline immunosuppression. IL-23 pathway inhibitors demonstrated favorable efficacy and safety in this vulnerable population, representing a promising strategy warranting further prospective evaluation.

Introduction: This final long-term extension (LTE) analysis assessed long-term efficacy and safety of ustekinumab (UST) in the Asian patient subpopulation with ulcerative colitis (UC) in the UNIFI study.

Methods: Patients who completed 44 weeks of subcutaneous (SC) UST maintenance and agreed to enter the LTE continued maintenance therapy (UST 90 mg SC every 8 weeks [q8w] or 12 weeks [q12w] or placebo). The LTE lasted from week (WK) 44 through WK 220 (final safety visit), with the final efficacy visit at WK 200. At WK 56, randomized patients could receive a dose adjustment. Descriptive outcomes, such as symptomatic remission, full Mayo score outcomes, endoscopic improvement, and safety, were assessed.

Results: Forty-one randomized patients entered the LTE at WK 44 and continued UST treatment (UST 90 mg SC q12w, 46.3% [19/41] or q8w, 53.7% [22/41]) through WK 188. Symptomatic remission was maintained through WK 200 (62.5% and 37.9% of patients in the UST 90 mg SC q12w and q8w groups, respectively). At WK 200, 78.9% and 50.0% of patients in the UST 90 mg SC q12w and q8w groups, respectively, were in corticosteroid-free symptomatic remission. Full Mayo clinical remission/response rates at WK 200 were 58.8%/94.1% and 75.0%/100.0% in UST 90 mg SC q12w and q8w groups, respectively (observed). Endoscopic healing rates at WK 200 in the UST 90 mg SC q12w and q8w groups were 70.6% and 91.7%, respectively (observed). No unexpected safety concerns were observed.

Conclusions: Despite the small sample size which limited data interpretation, long-term UST 90 mg SC treatment is safe and efficacious in Asian patients with moderately to severely active UC demonstrating clinical benefit, consistent with the global population. In addition, Asian patients with relatively stable clinical condition may benefit from UST 90 mg SC when administered in a q12w treatment regimen given its sustained efficacy and low discontinuation rates.

Introduction: 5-Aminosalicylic acid (5-ASA, mesalamine) is the cornerstone for maintaining remission in mild-to-moderate ulcerative colitis (UC), with several formulations available. Nonadherence to mesalamine is associated with increased relapse risk; however, large-scale real-world data comparing adherence and relapse among different formulations remain limited. This study aimed to evaluate adherence and relapse risk among four 5-ASA formulations using a large Japanese healthcare database.

Methods: Using a Japanese nationwide claims database, we retrospectively analyzed UC patients who were prescribed any of four oral 5-ASA formulations - time-dependent mesalamine, pH-dependent mesalamine, multi-matrix system (MMX) mesalamine, or salazosulfapyridine - between 2008 and 2022. Adherence was assessed using the proportion of days covered (PDC), and relapse was defined as UC-related hospitalization or escalation of therapy. A Cox proportional hazards model was used to identify factors associated with relapse.

Results: Among 13,876 eligible patients, MMX mesalamine showed the highest adherence (mean PDC: 91.6%) and the lowest relapse rate (2.9%), while salazosulfapyridine had the highest relapse rate (14.8%). In multivariate analysis, pH-dependent mesalamine (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.51-0.72) and MMX mesalamine (HR, 0.53; 95% CI, 0.35-0.78) significantly reduced relapse risk compared to time-dependent mesalamine, whereas salazosulfapyridine (HR, 1.51; 95% CI, 1.32-1.73) significantly increased relapse risk.

Conclusion: MMX mesalamine was associated with the highest adherence and lowest relapse rates among the four 5-ASA formulations. These findings emphasize the importance of formulation choice in UC management.

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.

Background: Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is a chronic lifelong condition that affects the colon to a variable extent. Current treatments for IBD include aminosalicylate-based drugs, corticosteroids, antibiotics, immunomodulators, biologics, other small-molecule drugs, and surgical intervention. Nonetheless, treatment options are variably effective, associated with serious side effects, and often leave individuals at risk of relapse.

Summary: In this narrative review, we explore emu oil (EO), a naturally sourced agent, that may be utilised to broaden therapeutic options in IBD. The anti-inflammatory, antioxidant, reparative, and protective properties of EO have been attributed to its unique blend of fatty acids and non-triglyceride fraction. To date, several preclinical trials of orally administered EO have demonstrated these properties in a range of intestinal inflammatory conditions, showing reduced inflammation and mucosal damage, together enhancing intestinal healing.

Key messages: While EO remains an interesting candidate for future investigations, current knowledge is limited to animal models and its clinical relevance is yet to be defined. Well-designed clinical trials will be essential to determine the safety and efficacy of EO before it can be considered as a potential adjunct to conventional therapy for IBD.

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.