Crohn's & Colitis 360最新文献

Background: Transabdominal intestinal ultrasound (IUS) is a promising, non-invasive tool for monitoring ulcerative colitis (UC). This modality has the advantage of assessing intestinal inflammation transmurally, suggesting that UC can be considered a transmural disease. Determining what transabdominal IUS findings indicate in terms of histopathology would improve its value in assessing disease activity. However, associations between sonographic and histopathological findings have not yet been established for active UC. To address this gap, we investigated patients with active UC who underwent colectomy following IUS examination.

Methods: Patients who underwent total colectomy for severe active UC within 1 week of undergoing transabdominal IUS at our facility between December 2020 and March 2023 were consecutively included in this study. Sonographic and histopathological findings were compared for each colonic segment in these patients.

Results: Four patients underwent IUS 3-6 days before colectomy, which was performed due to insufficient response to medical treatment. IUS findings, particularly loss of bowel stratification and increased color Doppler signals, were associated with severe inflammation and vascular proliferation in the transmural colon, including the subserosa. Thickened muscularis propria was also observed in inflamed colonic segments; this may have contributed to the increased bowel wall thickness according to IUS.

Conclusions: This is the first report comparing IUS findings and transmural pathological features in active UC. It provides an imaging atlas and clinical insights into the role of IUS in determining transmural histopathological inflammatory status in patients with active UC.

Background: Patient-reported outcomes (PRO) are key outcome measures in inflammatory bowel disease (IBD) trials. Typically, missing PRO data are imputed as treatment failures, even for patients completing trials with objective endpoints such as endoscopic data corroborating treatment effectiveness. This study investigated whether the final trial readout would change if PRO data imputation were more aligned with clinical practice.

Methods: Post-hoc analyses from two negative ulcerative colitis phase 3 etrolizumab trials: LAUREL and HICKORY. Non-responder imputation (NRI), last observation carried forward (LOCF), and hybrid methods using multiple imputation were utilized to handle missing PRO data for study completers. Treatment effects (TE) on clinical remission were compared. Monte Carlo simulations were used to evaluate the performance of various imputation methods.

Results: Among completers, 15% in LAUREL and 11% in HICKORY had missing PRO data at the end of the maintenance period. The majority of patients with only PRO missing were in etrolizumab arms, especially for endoscopic responders. NRI resulted in a 3%-5% decrease in TE estimates compared to LOCF and hybrid methods. Monte Carlo simulations confirmed that NRI can underestimate TEs and reduce power. While LOCF can mitigate this bias and power loss, the hybrid method produces the most unbiased and robust results.

Conclusions: Appropriately handling missing PRO data in patients completing treatment can reduce bias and improve the validity and reliability of efficacy analysis, potentially enhancing the ability of detecting therapeutic effects. This strategy should be considered in future clinical trials of IBD.

Clinical trial registration: LAUREL (NCT02165215) and HICKORY (NCT02100696).

Background: Janus kinase inhibitors (JAKi), including tofacitinib and upadacitinib, are small-molecule medications effective in treating inflammatory bowel disease (IBD) and other immune-mediated disorders. In adult IBD clinical trials for JAKi, acne is a commonly reported adverse event. There are currently no data on the prevalence of acne in pediatric patients with IBD treated with JAKi. In this manuscript, we sought to estimate the local prevalence, characteristics, and treatment patterns of JAKi-induced acne among pediatric patients with IBD.

Methods: We completed a retrospective chart review of children (age <18 years) treated with JAKi for IBD at Children's Hospital Colorado from 2019 to 2024. Demographics, IBD characteristics, and acne characteristics and treatment patterns were extracted from the electronic medical record.

Results: Twelve of 60 (20%) patients treated with JAKi for IBD subsequently developed acne during JAKi treatment, three times greater than rates observed in adult randomized controlled trials. Over 50% of patients were referred to dermatology. The most common treatments used were topical retinoids (4 patients), benzoyl peroxide wash (3 patients), topical clindamycin (3 patients), and oral isotretinoin (2 patients). One patient required JAKi discontinuation given the severity of acne, while another had improved acne with decreased dosing.

Conclusions: In this single-center cohort study, acne was a common adverse event among pediatric patients taking JAKi for IBD. Referral and treatment patterns in our cohort varied greatly, which demonstrates the need for a multidisciplinary approach and larger prospective studies to discern the prevalence, characteristics, and treatment response of JAKi-induced acne to inform risks and benefits.

Background: Erythema nodosum (EN) is an inflammatory condition marked by tender, red nodules, typically on the extensor limbs. Though often linked to IBD activity, its association with objective markers like inflammatory labs or endoscopic findings remains unclear. This study examined the relationship between EN and objective inflammation in IBD patients.

Methods: At a tertiary clinic with over 6500 patients, individuals with active EN were identified. Patients with active EN were identified, and symptomatic disease activity was assessed. Objective assessments included endoscopy, cross-sectional imaging (CT/MRI), fecal calprotectin, and CRP. Descriptive statistics compared objective and subjective disease activity in relation to EN.

Results: Of 169 patients with documented EN, 95 had at least one objective assessment within our timeframe and were included. The mean age at EN presentation was 32 years; most had Crohn's disease (80%) and were female (75%). Among CD patients, 93% had colonic involvement and 32% had penetrating disease. A total of 77 (74%) patients had gastrointestinal symptoms at the time of EN presentation, and 84 (81%) had objective evidence of active disease. Endoscopy was performed in 66% of cases, with 58 patients (84%) showing active inflammation. Among CD patients, 53% had mucosal ulcerations, while 67% of UC patients had severe disease (Mayo E3).

Conclusions: In this cohort, most patients presenting with EN had both symptomatic and objective signs of intestinal inflammation. These findings support the use of objective testing in IBD patients with EN and suggest EN may indicate a more severe or complicated disease course.

Introduction: Enteroclysis provides a whole picture of mucosal and wall-structural information that is advantageous in assessing small intestinal Crohn's disease (CD). Leucine-rich alpha-2-glycoprotein (LRG) is an acute-phase protein that has been shown to be increased in active CD. We sought to explore the association of LRG with the presence of typical CD findings in enteroclysis.

Methods: Patients with small intestinal CD whose serum LRG and C-reactive protein (CRP) were measured within 30 days before or after enteroclysis were selected, and were categorized by the presence of longitudinal ulcer, cobblestone appearance, and stricture/narrowing. Levels of LRG were compared by the type and the extent of lesions. Detection performances of LRG and CRP were compared for the presence of each type of lesion.

Results: Serum LRG levels were significantly higher in patients who had enteroclysis findings than patients with no findings (23.5 ± 9.2 vs. 12.8 ± 3.0 μg/dL, P < .00001). The level of LRG was not affected by disease extent or history of bowel resection. LRG over 16.3 μg/dL had good detection accuracy for the presence of CD lesions with an area under the receiver operating characteristic curve of 0.85 (95% confidence interval: 0.75-0.95). The association of LRG with the presence of CD-specific lesions was significantly higher than CRP, especially for the presence of stricture/narrowing (AUC: 0.82 vs. 0.67, P = .005) and longitudinal ulcer (AUC: 0.93 vs. 0.80, P = .017).

Conclusion: Elevation of serum LRG is associated with the presence of typical CD lesions in the small intestine that may be found in entericlysis.

Background: The conceptual context of wellbeing for people living with inflammatory bowel disease (IBD) is complex and encompasses many dimensions. Here, we employed a wholly patient-led analysis to provide a unique "patient first" narrative on wellbeing and IBD.

Methods: Our report draws on data from a Wellbeing Survey led by the Glasgow and Edinburgh IBD Science team as part of the MUSIC IBD cohort study (www.musicstudy.uk) with over 1375 IBD respondents in 2023 from the United Kingdom and globally. Our public and patient involvement (PPI) group utilized unstructured patient-reported experiences and conducted a high-level topic analysis and based their own lived experience of IBD to explore and assimilate the 415 free-text responses on the priorities and unmet needs of our IBD participants. Within the PPI group, a transparent structure of patient-led analysis, identification of key topic areas, discussion, and finally writing was agreed at the start of the project with minimal input from the clinical team.

Results: The analysis provided an in-depth exploration of several key themes affecting wellbeing in IBD patients. Of interest, the PPI group discussed and explored themes such as "what does remission mean?," access to care, expectations of self-management, mental and women's health. The patient narratives highlighted the variability of IBD experiences, the interconnectedness of these issues, and the importance of holistic, patient-centric approaches to care. The findings emphasize the necessity for improved support, both within and beyond healthcare settings. The findings are written and presented by our PPI group to provide viewpoints that resonate directly with people living with IBD.

Conclusion: Our patient-led research approach demonstrates that allowing patients to lead in analysis ("taking the reins") and reporting provides deeper and impactful insights into IBD experiences. By shifting the lens of analysis via the patient when integrating their perspectives into wellbeing. This study thus, advocates for a patient-dominant approach to research and care, which can provide unique insights into ways to improve outcomes and to address the complexities of living with IBD.

Background: Fatigue is a common and disabling symptom in pediatric inflammatory bowel disease (IBD), often persisting even during clinical remission and reflecting a multifactorial origin. Despite its significant impact on patients' lives, it remains under-recognized. The IMPACT-III and IMPACT-III-P questionnaires facilitate fatigue assessment within a biopsychosocial framework of health-related quality of life (HRQOL).

Methods: In this multicenter study supported by the Spanish Society of Pediatric Gastroenterology, Hepatology and Nutrition (SEGHNP), 382 patients aged 10-17 years and their caregivers from 37 hospitals completed the IMPACT-III and IMPACT-III-P questionnaires between February 2021 and June 2023. Fatigue-related items were analyzed, and predictive models were developed using univariate and multivariate logistic regression.

Results: A total of 370 patient questionnaires were included in the analysis. The median age at diagnosis was 11.3 years (interquartile range [IQR] 8.7-13.3), and at assessment, 14.4 years (IQR 12.4-16.1). Males represented 56% of the cohort, and 61.1% had Crohn's disease. Treatments included immunosuppressants (44.6%), 5-ASA (33.7%), biologics (30.8%), corticosteroids (6%), and other therapies (27.8%). Fatigue was reported by 81.1% of patients, including 77.5% of those in clinical remission. Severe fatigue was significantly associated with female sex, older age, active disease, and dietary treatment. Conversely, absence of fatigue was independently associated with male sex, earlier pubertal stage, and not receiving biologics. Notable discrepancies were observed between patient and caregiver perceptions of energy levels. Fatigue correlated with significantly lower HRQOL scores across all IMPACT-III domains. In Crohn's disease, the strongest impacts were observed in the social and systemic domains, whereas in ulcerative colitis, emotional and physical domains were more affected. Patients without severe fatigue consistently scored higher in all domains.

Conclusion: Fatigue is a highly prevalent and multifactorial symptom in pediatric IBD, with a marked negative impact on quality of life, even in clinical remission. The IMPACT-III and IMPACT-III-P questionnaires are valuable tools for its assessment and highlight the need for routine, systematic evaluation of fatigue to guide holistic and individualized management strategies.

Background: At the end of the past century, infliximab (IFX), the first-in-class biological therapy approved in inflammatory bowel disease (IBD), dramatically modified the therapeutic armamentarium. The recent development of subcutaneous (SC) formulations of IFX offers a promising alternative, with the potential to improve patient convenience, adherence, and overall outcomes. This review explores the clinical evidence supporting the initiation of SC IFX and the transition from intravenous (IV) to SC IFX.

Methods: Comprehensive review using MEDLINE (source PUBMED).

Results: Comparative studies have shown that SC IFX is associated with higher IFX serum concentration levels than IV, fewer neutralizing antibodies and similar levels of remission. Real-world studies have confirmed that switching from IV to SC IFX 120 mg is well accepted with a low risk of relapse. The ease of at-home administration has been associated with improved patient satisfaction and reduced healthcare burdens. The adoption of SC IFX could profoundly change the therapeutic landscape, offering a more patient-centered approach to long-term disease control but some questions remain, particularly about the place of IFX in certain populations.

Conclusion: In this article, we reviewed the known and unknown data on SC IFX to provide a comprehensive summary and assist IBD physicians in integrating this knowledge into everyday clinical practice.

Background: Recent advances in biomarkers have identified at-risk cohorts for inflammatory bowel disease (IBD), and potential interception strategies to prevent disease onset are in progress. We sought to understand patient and family members' views on IBD prevention, as they are key stakeholders in future adoption of prevention recommendations.

Methods: A workgroup of patient advocacy organizations and researchers adapted a survey for completion by the IBD community residing in the United States. All responses were anonymous. Descriptive results, and comparisons, were undertaken of pooled responses.

Results: One thousand five hundred forty-five respondents completed the survey. Most respondents (93%, n = 1,421) would be interested in taking a test to predict their or their family's risk of developing IBD in the future. Almost all respondents were interested in taking preventative treatment to prevent IBD; 40% expressed an unconditional interest in the treatment, but 59% reported it would be dependent on the risks and effectiveness of the treatment. Lifestyle measures were the most preferred option to prevent IBD. There was no significant difference in proportion of patients who were willing to take a test or prevention treatment based on relationship to IBD (have IBD, first-degree relative of someone who has IBD, or parent of someone with IBD).

Conclusions: Most people affected by IBD in the United States agree with taking proactive measures to prevent IBD. A lifestyle intervention (diet, exercise) is favored over a pharmaceutical approach by these respondents. Relationship to IBD did not influence the magnitude of the agreement.

Introduction: Treat-to-target (TTT) for patients with inflammatory bowel disease (IBD) involves treating to clinical and endoscopic remission. Despite control of clinical symptoms, many patients may not achieve endoscopic remission. Real-world prevalence and patient acceptance of staying on current advanced therapy vs switching in this scenario is not well defined. The aim of this study are to report real-world prevalence of symptomatic and endoscopic/radiologic discordance and patient and provider preferences regarding stay or switch advanced therapy in this setting.

Methods: In the QUOTIENT trial, we performed screening exercises to estimate the prevalence of symptomatic and endoscopic/radiologic discordance using detailed screening logs for eligible patients. Sites completed screening exercises to identify what proportion of patients are eligible to participate in the QUOTIENT trial and willingness to participate.

Results: A total of 761 patients were screened for QUOTIENT with complete data. Of patients in corticosteroid-free symptomatic remission on an advanced therapy, 12% had moderate-to-severe endoscopic inflammation. The most common reason for declining to participate was patients' preference to stay on current advanced therapy (39%). Only 11% preferred switching to advanced therapy as a reason to decline participation.

Conclusions: Among patients with IBD who have achieved corticosteroid-free symptomatic remission on advanced therapies, real-world rates of achieving endoscopic remission or mild endoscopic activity are significantly higher than suggested by clinical trials. We observed a strong patient preference to stay on their current advanced therapy, rather than switching to an alternative agent, which contrasts with the providers' framework for treat-to-target.