Journal of Crohn's & colitis最新文献

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.

Background and aims: Assessment of fibrosis in intestinal strictures in Crohn's disease (CD) could contribute to clinical decision-making. Our recent studies demonstrated that endoscopic photoacoustic (PA) imaging can quantify the progression of intestinal fibrosis based on its collagen content and its mechanical stiffness. The aim of this study was to evaluate the feasibility and diagnostic reliability of a PA-ultrasound balloon catheter in assessing intestinal fibrosis.

Methods: Acute colonic colitis or chronic inflammation with fibrosis was induced in rabbits using intrarectal trinitrobenzene sulfonic acid. The affected distal colon was assessed through PA imaging in vivo and microelastometry ex vivo. Quantitative measurements were derived from the images and compared with histopathology. We also examined the feasibility of the catheter in a human subject with CD strictures.

Results: Quantitative PA imaging measurements in vivo detected an increased collagen/hemoglobin ratio of 1.42 arbitrary units (P < .001) in the chronic high fibrosis rabbit group compared to the acute colitis/low fibrosis and normal groups. The imaging results in vivo also showed an increased relative tissue stiffness of 4.27 kPa (P < .001) in the high fibrosis group compared to the low fibrosis and normal groups, which agrees with ex vivo microelastometer measurements. The human subject study demonstrates sufficient light penetration and signal-to-noise ratio for assessing intestinal fibrosis during a standard ileo-colonoscopy procedure.

Conclusion: Our novel imaging catheter shows reliability in differentiating the changes in molecular components and mechanical properties during the progression of intestinal fibrosis. This catheter-based approach is fully compatible with clinical colonoscopy procedures.

Background and aims: Inflammatory bowel disease (IBD) often affects multiple relatives, pointing toward shared genetic and/or environmental factors. This study evaluates the importance of known IBD risk variants, and of genetic determinants of smoking in such multiplex families.

Methods: We studied 65 IBD multiplex families, comprising 146 Crohn's disease (CD), 33 ulcerative colitis (UC), and 111 unaffected relatives. All families had at least 3 affected first-degree relatives. Common variant and rare variant polygenic risk scores (PRS and rvPRS) in these individuals were calculated and compared to 2040 sporadic IBD cases (1198 CD, 842 UC) and 598 unrelated controls. Associations for PRS, rvPRS, and smoking PRS were assessed using univariable and multivariable models.

Results: Within multiplex families, unaffected relatives had lower PRS than affected relatives (P = 0.01), but still higher scores than unrelated controls (P = 0.01). Interestingly, rvPRS did not differ between affected and unaffected relatives. PRS and rvPRS showed substantial heterogeneity across families; for example 10 families (2 for rvPRS) had PRS below unrelated controls, while 27 (6 for rvPRS) scored above sporadic cases. No correlation was found between PRS and rvPRS at the individual or family level. Smoking-related PRS were not associated with familial IBD.

Conclusions: Multiplex IBD families show diverse genetic architecture, with almost half showing a high burden of common and/or rare risk variants. While genetic predispositions to smoking influences IBD risk in sporadic cases, it provides limited insights into familial IBD. These findings highlight the genetic complexity within multiplex families and the need for tailored research approaches such as risk stratification and genetic screening strategies.

Advanced combination treatment (ACT)-the combination of two advanced agents such as biologics or small molecules-has emerged as a promising strategy in the management of inflammatory bowel disease refractory to conventional treatment, with severe extraintestinal manifestations, or with coexisting immune-mediated inflammatory diseases. ACT including complementary mechanisms of action aims to overcome the therapeutic ceiling observed with monotherapy. Its rationale is supported by preclinical and mechanistic data demonstrating synergistic immunological effects when distinct inflammatory pathways are targeted simultaneously. Although observational studies report pooled clinical and endoscopic remission rates of approximately 60% and 30%, respectively, the quality of evidence remains very limited. Most studies are retrospective, heterogeneous in patient populations and treatment regimens, and often report outcomes in aggregate, precluding firm conclusions regarding the efficacy of specific drug combinations. The two and only randomized controlled trials available to date have shown acceptable safety profiles but limited or no clear superiority of ACT over monotherapy. Safety data are reassuring, with no significant increase in serious adverse events. The optimal duration of ACT remains uncertain; while de-escalation to monotherapy following deep remission is feasible in selected patients, relapse rates vary, emphasizing the need for individualized treatment decisions and long-term follow-up. High treatment costs also pose a barrier to widespread adoption of ACT, though biosimilars may help offset these concerns. In summary, ACT may represent a potentially valuable therapeutic option in selected high-risk or treatment-resistant patients with inflammatory bowel disease; however, its true clinical benefit remains uncertain and requires confirmation through robust, well-powered randomized controlled trials.