Journal of Crohn's & colitis最新文献

Background and aims: Intestinal ultrasound (IUS) is increasingly used to monitor treatment efficacy in inflammatory bowel disease (IBD) trials. However, standardized definitions for response, remission, and optimal assessment timing remain undefined. An international expert consensus meeting was held to establish IUS endpoints for clinical trials.

Methods: A panel of 35 international gastroenterologists and radiologists participated in a modified Delphi process, reviewing the literature and developing consensus statements. Agreement was defined as at least 75% consensus.

Results: Consensus was reached on 150 statements across four domains: general IBD (30 statements), luminal Crohn's disease (CD) (43), perianal CD (51), and ulcerative colitis (UC) (26). For luminal CD and UC, ultrasound response was defined by: (1) a ≥25% reduction in bowel wall thickness (BWT) from baseline, or (2) multifactorial improvement, combining BWT reduction with ≥1 grade decrease in color Doppler signal (CDS) or another IUS parameter. Assessments were set at weeks 4-8 for the colon and week 12 for the terminal ileum. Ultrasound remission in luminal CD was defined as: (1) BWT normalization (≤3 mm) or (2) normalization of multiple parameters, including BWT, CDS, and all other IUS parameters. Similar remission criteria were proposed for UC, but the sigmoid BWT normal range (3-4 mm) remained uncertain. The bowel ultrasound score (BUSS) for CD and the Milan ultrasound criteria (MUC) for UC were supported as standardized scoring systems for trials.

Conclusion: This consensus provides standardized IUS definitions to enhance consistency in IBD trials, supporting the integration of IUS in future research.

Background and aims: This study aims to evaluate the real-life durability of biologic therapies and to identify factors associated with biologic persistence in pediatric inflammatory bowel disease (IBD).

Methods: We analyzed data from the IBD-registry of the Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition (SIGENP) of patients initiating biologics between 2009 and 2022 and ≥1-year follow-up.

Results: A total of 1184 patients (747 with Crohn's disease [CD], 437 with ulcerative colitis or IBD unclassified [UC/IBD-U]) were included, accounting for 1709 treatment courses. The median follow-up was 43 months (interquartile range 28-64). Overall, 33% received a second-line biologic, 9% third-line, and 2% fourth-line. First-line biologic durability was significantly lower in UC/IBD-U vs CD, with inferior persistence at 1, 2, and 3 years (61%, 51%, and 44% vs 88%, 75%, and 67%; hazard ratios [HR]: 1.5, 95% confidence interval [CI] 1.2-1.9, P = .002). In CD, infliximab had inferior durability then adalimumab (72%, 59%, and 50% vs 91%, 82%, and 77%; HR 2.0, 95% CI, 1.5-2.7, P < .0001). In both CD and UC/IBD-U, age <6 years was a risk factor for treatment discontinuation (HR 1.8, 95% CI, 1.2-2.7, P < .01) while therapeutic drug monitoring (TDM) emerged as protective (HR 0.5, 95% CI, 0.4-0.7, P < .0001). Combination with an immunomodulator had no significant impact on durability (HR 0.9, 95% CI, 0.8-1.2, P = .54).

Conclusions: Biologic persistence varied by disease type and biologic agent. TDM was associated with longer treatment durability, while combination therapy had a limited effect. Further prospective studies are needed to refine biologics optimization strategies in pediatric IBD.

Background and aims: Janus kinase inhibitors (JAKi) provide effective treatment for ulcerative colitis (UC), but inadequate response (IR) or intolerance occurs frequently. This study aimed to assess the effectiveness of a second JAKi in a real-world UC cohort.

Methods: A retrospective multicenter cohort study encompassing 19 UK hospitals was undertaken. Primary outcome was clinical remission (Simple Clinical Colitis Activity Index/partial Mayo Score ≤ 1) at weeks 8 and 24, based on available assessments. Biochemical (CRP ≤ 5mg/L and fecal calprotectin ≤ 200µg/g) and endoscopic (Ulcerative Colitis Endoscopic Index of Severity/Mayo Endoscopic Subscore ≤ 1) remission were also assessed.

Results: A total of 131 patients with active UC were included. The majority (60%) had exposure to ≥3 advanced therapies and 50% required corticosteroids at induction. Clinical remission rates were 59% and 51% at weeks 8 and 24. Biochemical and endoscopic remission rates were 61% and 60% at week 8, and 47% and 32% at week 24. All disease activity parameters significantly reduced by week 8 (P < .001). At week 24 no difference was detected in clinical remission rates between those with primary non-response (42%) or secondary loss of response (52%) to their first JAKi (P = .518). Clinical remission did not differ between upadacitinib (54%) and filgotinib (36%), P = .253. Adverse events occurred in 27% of patients, and serious adverse events in 8%.

Conclusions: In this highly refractory cohort with active UC a second JAKi effectively achieved remission following IR to first JAKi. Type of first JAKi failure did not appear to influence clinical remission. No new safety signals were found.

Background and aims: We investigated the correlations between patient-reported outcome measures (PROMs) and other measures of inflammatory bowel disease (IBD) activity.

Methods: A systematic literature review was performed up to June 2022. Searches were conducted in PubMed, Scopus, and Web of Science. A descriptive analysis was performed. The search protocol was registered in PROSPERO (CRD42022383899).

Results: Nineteen studies assessed correlations between PROMs and clinical, endoscopic, and laboratory measures of disease activity in IBD. In Crohn's disease (CD), weak positive correlations were reported for PROMs (eg, the 2 item patient-reported outcome [PRO-2], mobile Health Index [mHI] for CD) and endoscopic scores, more often the Simple Endoscopic Score for CD (SES-CD). In ulcerative colitis (UC), PROMs like PRO-2, the Monitor IBD at Home rectal bleeding item, and the mHI showed weak-to-moderate correlations with the Mayo endoscopic subscore (MES). PROMs also demonstrated limited concordance with laboratory measures such as fecal calprotectin (FCP) and C-reactive protein (CRP) in both CD and UC. The substantial heterogeneity in study designs precluded a structured analysis.

Conclusions: Although current PROMs offer valuable complementary insights into IBD control from the patient's perspective, they cannot replace objective measures of IBD activity. Future research should focus on refining PROMs and generating composite indices to improve their accuracy and usefulness.

Background & aims: Despite debilitating symptoms, no standardized disease severity index exists for microscopic colitis (MC). This gap hinders alignment with U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) standards, which emphasize the importance of patient-reported outcome measures (PROMs) in new therapy approval. This study aimed to validate the Microscopic Colitis Symptom Questionnaire (MCSQ) and develop the Microscopic Colitis Score (MCS), a novel disease severity index.

Method: This prospective, multicenter study included 131 patients with biopsy-confirmed MC (67 remission, 64 active disease). Patients completed MCSQ and health-related quality of life (HRQoL) assessments [IBDQ-32, Short Health Scale (SHS)] at baseline and follow-up. Clustering analysis systematically identified distinct disease severity groups. MCS was developed as a composite score derived from MCSQ.

Results: Factor analysis revealed a three-factor MCSQ model with good internal consistency (Cronbach's alpha = 0.88). Test-retest reliability (intraclass correlation coefficient = 0.88) and responsiveness to treatment (P < .01) of all MCSQ items were high. MCS, ranging from 0 (asymptomatic) to 15 (maximum symptoms), correlated strongly with HRQoL measures such as IBDQ-32 total score (rp=-0.78), IBDQ-32 bowel symptoms (rp=-0.80), and SHS bowel symptoms (rp=0.69). Receiver-operating characteristic curves indicated that MCS could accurately identify patients in remission [as per Hjortswang criteria; area under the curve (AUC) = 0.85], as well as mild (AUC = 0.97), moderate (AUC = 0.93), or severe disease (AUC = 0.96).

Conclusions: MCSQ and MCS are valid, reliable, and responsive tools that meet FDA and EMA standards. Both accurately reflect the diverse symptoms of MC. Compared to the binary Hjortswang criteria, MCS provides a nuanced evaluation of disease activity and holds promise for assessing therapeutic efficacy in future trials.

Glucagon-like peptide-1 receptor agonists are increasingly recognized for their potential dual benefit in inflammatory bowel disease (IBD), offering metabolic advantages alongside emerging anti-inflammatory, immunomodulatory, and gut barrier-enhancing effects. Pre-clinical data demonstrate attenuation of inflammation, preservation of epithelial integrity, and modulation of the microbiome in colitis models. Early retrospective studies in patients with IBD suggest improved clinical outcomes, such as reduced hospitalization and surgery rates, particularly in those with obesity. Glucagon-like peptide-1 receptor agonists are already widely used for obesity and diabetes, including increasing self-administration by patients outside medical supervision. Their impact on drug absorption, safety in gastrointestinal disease, and interactions with existing IBD therapies require further exploration. This review synthesizes the mechanistic rationale, pre-clinical evidence, and clinical data to date, highlighting the potential utility and safety considerations of glucagon-like peptide-1 receptor agonists in IBD and emphasizes the need for robust prospective trials to ascertain their safety and efficacy in this patient population.

Background & aims: Endoscopic healing (EH) is recognized as a long-term treatment goal for patients with ulcerative colitis (UC). We investigated whether transmural healing (TH) in UC as assessed by intestinal ultrasound (IUS) is associated with improved outcomes compared to EH alone.

Methods: We performed a retrospective study in a tertiary center on patients with left-sided or extensive UC on stable maintenance treatment who had EH [Mayo Endoscopic Subscore (MES) ≤1) and an IUS performed within 6 months of an endoscopy with no treatment alterations between IUS and endoscopy. TH was defined as bowel wall thickness (BWT) <3 mm. The primary outcome was relapse-free survival in patients with and without TH.

Results: A total of 61 patients (MES 0: 44.3%; MES 1: 55.7%) with a median follow-up of 20 months were included. On IUS, 72% of patients had TH. Twenty-three patients had a relapse (first-year relapse risk: TH: 7.5% vs no TH: 29.4%, P = .004; MES 0: 3.7% vs MES 1: 20.8%, P = .059). In multivariate Cox regression, female gender [hazard ratio (HR), 2.63; 95% CI 1.05-6.58; P = .039], two or more previous advance therapies (HR, 4.06; 95% CI 1.08-15.28; P = 0.038), and non-TH (HR, 3.99; 95% CI 1.31-12.20; P = .015) were associated with a relapse whereas EH level (MES 0 vs MES 1) was not an associated factor (HR, 1.06; 95% CI 0.32-3.55; P = .924).

Conclusions: In UC patients TH is associated with lower relapse risk compared to EH alone. These findings imply that IUS is a non-invasive, low-cost alternative to endoscopy for stratifying UC patients for risk of relapse.