Intestinal Research最新文献

Background/aims: Previous literature suggests that the response of patients with ulcerative colitis to vedolizumab may be affected by previous biologic therapy exposure. This real-world study evaluated vedolizumab treatment effectiveness in biologicnon- naïve patients.

Methods: This was a multicenter, retrospective, observational chart review of records from 16 hospitals in Japan (December 1, 2018, to February 29, 2020). Included patients who had ulcerative colitis, were aged ≥ 20 years, and received at least 1 dose of vedolizumab. Outcomes included clinical remission rates from weeks 2 to 54 according to prior biologic exposure status and factors associated with clinical remission up to week 54.

Results: A total of 370 eligible patients were included. Clinical remission rates were significantly higher in biologic-naïve (n=197) than in biologic-non-naïve (n=173) patients for weeks 2 to 54 of vedolizumab treatment. Higher clinical remission rates up to week 54 were significantly associated with lower disease severity (partial Mayo score ≤ 4, P= 0.001; albumin ≥ 3.0, P= 0.019) and the duration of prior anti-tumor necrosis factor α (anti-TNFα) therapy (P= 0.026). Patients with anti-TNFα therapy durations of < 3 months, 3 to < 12 months, and ≥ 12 months had clinical remission rates of 28.1%, 32.7%, and 60.0%, respectively (P= 0.001 across groups).

Conclusions: The effectiveness of vedolizumab in biologic-non-naïve patients was significantly influenced by duration of prior anti-TNFα therapy. (Japanese Registry of Clinical Trials: jRCT-1080225363).

Background/aims: Patients with ulcerative colitis (UC) in remission commonly restrict thir lifestyle to prevent relapse; however, the effectiveness and impact on quality of life (QOL) is unclear. This study investigated whether lifestyle restrictions are associated with relapse reduction and assessed their impact on QOL.

Methods: This multicenter, prospective cohort study was conducted in Japan (2018-2021) via the YOURS registry, enrolling patients with UC in clinical remission. Patients were followed for 2 years. A baseline questionnaire evaluated lifestyle restrictions in diet, work/study/housework, and physical exercise. QOL was assessed by Disease Impact Scale every 3 months during the first year of follow-up. Associations of lifestyle restrictions with relapse and QOL were assessed by Cox regression analysis and linear mixed-effects models, respectively.

Results: Among 911 patients in clinical remission for > 90 days, 63% had adopted dietary avoidance; 47%, work/study/housework avoidance; and 8%, physical exercise avoidance. Overall, 216 patients relapsed. Lifestyle restrictions were not associated with reduced risk of relapse (multivariableadjusted hazard ratios [95% confidence interval]: dietary avoidance, 1.08 [0.81-1.44]; and work/study/housework avoidance, 1.14 [0.87-1.50]); physical exercise avoidance was associated with increased relapse (multivariable-adjusted hazard ratio, 1.58; 95% confidence interval, 1.02-2.44). All lifestyle restrictions were associated with impaired QOL (P <0.01).

Conclusions: Lifestyle restrictions were not associated with relapse reduction in patients with UC; however, they were associated with impaired QOL. Clinicians should engage in evidence-based discussions with patients with UC in remission regarding lifestyle restrictions (UMIN Clinical Trials Registry; UMIN000031995).

Background/aims: Pouchitis is a common complication in patients with ulcerative colitis (UC) following colectomy with ileal pouch-anal anastomosis (IPAA). Recent studies have identified a novel autoantibody against integrin αvβ6 in patients with UC, correlated with disease activity. This study aimed to assess the association between serum anti-integrin αvβ6 antibody levels and pouch inflammation in patients with postoperative UC.

Methods: Serum anti-integrin αvβ6 antibodies were measured using enzyme-linked immunosorbent assay in patients after IPAA, patients with UC, and controls.

Results: We examined sera from 71 subjects, including 28 patients who underwent IPAA, 23 controls, and 20 patients with mild and moderate-to-severe UC. Post-IPAA, patients with UC had higher median anti-integrin αvβ6 levels than that of controls (P<0.001) but lower than that of patients with active UC (P=0.001). Patients with pouchitis had higher antibody levels than those without (P=0.047). The receiver operating characteristics curve for anti-integrin αvβ6 showed an area under the curve of 0.724. The pouchitis activity index endoscopic sub-score was correlated with antibody levels (r= 0.48, P=0.011).

Conclusions: Serum anti-integrin αvβ6 antibody levels remain elevated in patients with UC even after total colectomy, and were significantly higher in patients with pouchitis than in those without. This antibody could be a novel and useful biomarker for the diagnosis of pouchitis and assessment of disease activity.

Background/aims: Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). However, its efficacy, safety, and the appropriate dosage have not been extensively investigated in the Japanese population.

Methods: This phase 2, multicenter, randomized, double-blind, placebo-controlled dose-ranging, 12-week trial was carried out among Japanese patients with moderately to severely active UC. Patients were randomized 1:1:1 to receive etrasimod 1 mg once daily (QD), etrasimod 2 mg QD, or placebo. The primary efficacy endpoint was the proportion of patients achieving clinical remission at week 12. Secondary efficacy endpoints and treatmentemergent adverse events (TEAEs) were also investigated. Efficacy endpoints were presented as proportions of patients achieving each outcome.

Results: Overall, 17, 19, and 18 patients received etrasimod 1 mg QD, etrasimod 2 mg QD, and placebo, respectively. One patient receiving etrasimod 1 mg (6.7%), 5 patients receiving etrasimod 2 mg (26.3%), and no patients receiving placebo (0%) achieved clinical remission. More patients receiving etrasimod versus placebo achieved secondary endpoints, except endoscopic normalization, at week 12. TEAEs were experienced by 9 patients receiving etrasimod 1 mg (52.9%), 13 patients receiving etrasimod 2 mg (68.4%), and 10 patients receiving placebo (55.6%). None of the TEAEs were serious and none experienced by patients receiving etrasimod led to treatment discontinuation.

Conclusions: Overall, etrasimod 2 mg QD for up to 12 weeks appeared efficacious and safe in these Japanese patients with moderately to severely active UC. All TEAEs were mild to moderate in severity. (ClinicalTrials.gov: NCT05061446).

Background/aims: Accurate assessment of disease activity is crucial for effective management and treatment of ulcerative colitis (UC). This study evaluated the correlation between clinical, endoscopic, and histologic measures of disease activity in UC.

Methods: Clinical, biochemical, endoscopic, and histologic disease activity was studied in 347 patients with UC. Agreements among various histologic classification systems, namely the Geboes Score (GS), Continuous GS, Nancy Index (NI), and Robarts Histopathology Index (RHI), were analyzed. The predictive accuracy of fecal calprotectin (FC) for endoscopic and histologic remission was assessed.

Results: We demonstrate a fair to moderate correlation between clinical, endoscopic, and histologic measures of disease activity in UC. There was a robust concordance among GS, Continuous GS, NI, and RHI in distinguishing between patients in histologic remission or activity. The NI detected 75% of patients who met the remission criteria according to the RHI, whereas the RHI identified all patients in remission as defined by the NI. FC levels below 150 μg/g had >70% accuracy in predicting endoscopic remission. FC levels below 150 μg/g showed ≥80% accuracy, and FC levels below 100 μg/g demonstrated ≥ 85% accuracy in predicting histologic remission, regardless of the scoring index applied. Elevated FC levels were associated with both acute and chronic inflammatory infiltrates in biopsy samples.

Conclusions: FC is a reliable predictor of histologic remission, with higher accuracy at lower thresholds. The GS, Continuous GS, NI, and RHI demonstrate comparable performance. FC could help stratify patients' need for colonoscopy for the assessment of endoscopic and histologic remission.

Background/aims: In today's age, celiac disease (CD) is no longer solely characterized by chronic diarrhea in a malnourished child. Obesity is gradually being acknowledged as part of CD's clinical course. Both conditions have been linked to alterations of gut microbiome. Given the difficulty of strict gluten-free diet adherence, there is a need for less restrictive adjunctive therapies. We aimed to investigate the prevalence of obesity in patients diagnosed with CD with the goal of developing new therapeutic approaches.

Methods: Baseline data from the National Institute of Health's All of Us Research Program, was used to evaluate the relationship between CD and obesity. A retrospective cohort study was conducted where groups of individuals with CD and without CD were matched by age range and health surveys. Statistical analysis with odds ratios (OR) with 95% confidence intervals (CI) were reported.

Results: The prevalence of obesity was 32.6% in the CD group compared to 18.4% in the control group (OR, 2.111; 95% CI, 1.914-2.328; P< 0.0001). Women accounted for a greater population of patients with CD and obesity. The largest percentage of patients with CD and obesity were older than 65 years. The highest percentage of individuals in both the experimental and control groups were white, followed by African Americans.

Conclusions: Our data shows a significant association between CD and increased prevalence of obesity. These results warrant further investigation into microbial changes and dietary exposures that affect the pathogenesis of both diseases.

Background/aims: Bowel urgency is an important symptom for quality of life determination in patients with ulcerative colitis (UC). Few clinical studies have focused on bowel urgency as an efficacy endpoint. Budesonide foam enema has shown efficacy for clinical and endoscopic improvement in mild-to-moderate UC. We evaluated the improvement of clinical symptoms (bowel urgency), safety, and treatment impact of twice-daily budesonide foam enema on the quality of life in patients with UC.

Methods: This open-label, multicenter, prospective observational study comprised a 4-week observation period assessing the effectiveness and safety of twice-daily budesonide foam enema. Mild-to-moderate UC patients who had bowel urgency were included. Patients collected data daily in an electronic patient-reported outcome system or logbooks. The primary endpoint was the rate of resolution of bowel urgency at the end of the 4-week observation period. The rate of bowel incontinence was also assessed.

Results: Sixty-one patients were enrolled. Of patients with a final evaluation, the rate of resolution of bowel urgency was 58.5% (31/53; 95% confidence interval, 44.1%-71.9%). Bowel urgency decreased over time, with a significant difference observed on day 7 versus day 0. Bowel incontinence showed a decreasing trend from day 5, with a significant difference confirmed on day 12 versus day 0. The clinical remission rate was 64.4% (38/59; 95% confidence interval, 50.9%-76.4%). One adverse event not related to budesonide rectal foam occurred.

Conclusions: The findings suggest that bowel urgency can be improved early with twice-daily budesonide foam enema. No new safety signals were observed.