Inflammatory Bowel Diseases最新文献

Immunometabolism exerts a bimodal action at the interface of extracellular immune response and intracellular metabolism, putting it at the center of many immune-mediated inflammatory disorders (IMIDs). Research has shown that immunometabolic pathways may act as a dual checkpoint for the inflammatory cycle to return the system to homeostasis by inactivating inflammatory pathways and shifting metabolism in favor of regulatory phenotypes. In addition, immunometabolic targets may act in non-immune cells such as epithelial and mesenchymal cells. Therefore, the therapeutic approach to targeting the uniquely robust mechanisms of immunometabolism may ameliorate aspects of IMIDs that remained to be addressed. Several emerging targets, including mitochondrial regulators (eg NLRX1), membrane-bound receptors (eg PLXDC2), and hormonal peptides (eg GLP-1), illustrate the diverse ways immunometabolism can be leveraged therapeutically. Preclinical models of inflammatory bowel disease (IBD) and other IMIDs have highlighted the bimodal immunoregulatory roles of these pathways. Preliminary clinical data support the potential utility of immunometabolic modulation, particularly in combination with existing therapies, to overcome the current therapeutic ceiling in clinical efficacy. Continued research is needed to validate the efficacy, safety, and mechanistic precision of immunometabolic agents across the spectrum of IMIDs.

Introduction: Rapid symptom relief is an important consideration for patients with ulcerative colitis (UC) experiencing a flare. Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active UC. We evaluated patient-reported symptomatic improvement from patients in the ELEVATE UC program.

Methods: This study was a post-hoc analysis of pooled daily e-diary data from patients with moderately to severely active UC receiving etrasimod or placebo in the phase III ELEVATE UC 52 and ELEVATE UC 12 trials. During the 12-week induction periods, patients self-reported stool frequency and rectal bleeding on days 1-28. Daily symptomatic response and symptomatic remission were calculated (partial modified Mayo Score).

Results: Overall, 787 patients (527 receiving etrasimod, 260 placebo) were included in the analysis. Etrasimod-treated patients had statistically significantly higher rates of symptomatic response and symptomatic remission during the first 28 days of therapy, with adjusted differences (95% CIs) reaching statistical significance from day 2 (5.6% [0.8-10.3], P = .022) to day 11 (4.7% [0.4-9.0], P = .034), respectively. In patients naïve to biologic/Janus kinase inhibitor therapy, symptomatic response was statistically significantly improved with etrasimod vs placebo from day 3 (8.9% [2.3-15.5], P = .008). Symptomatic improvement rates were similar with and without concomitant corticosteroid use.

Conclusions: In this post-hoc analysis, improvements in UC symptoms occurred in patients receiving etrasimod vs placebo from as early as day 2. These findings indicate a rapid onset of symptomatic effect with etrasimod treatment for moderately to severely active UC.

Clinicaltrials.gov numbers: NCT03945188, NCT03996369.

Background: Point-of-care intestinal ultrasound (IUS) is a non-invasive tool to evaluate inflammation in patients with inflammatory bowel disease (IBD). Limited studies have evaluated the role of IUS during routine clinical care. This study investigated the addition of IUS as part of routine clinic visits compared to standardized indices collected in real-world care to evaluate the role of IUS as a treat-to-target measure.

Methods: This cross-sectional study included pediatric patients (<18-years-old) with IBD who underwent IUS as part of clinical care. The primary outcome compared the accuracy of IUS with clinical indices versus clinical indices alone to predict biochemical disease activity using receiver operating characteristics. Secondary outcomes evaluated differences in bowel wall thickness (BWT) based on biochemical disease activity and level of clinical severity.

Results: The study included 92 patients with 136 IUS exams. The addition of IUS markers to clinical parameters improved prediction of biochemical activity in CD (AUC 0.71 versus 0.90; P = .004) and trended toward improvement in UC (AUC 0.83 versus 0.92; P = .067). Patients with active disease had higher BWT than those with quiescent disease. Median BWT for FCP activity was 4.2 mm (IQR: 2.7-5.0 mm) versus 2.0 mm (IQR: 1.6-2.7 mm; P < .001) for FCP remission (≤250µg/g). Optimal BWT thresholds to predict FCP > 250 ranged between 2.3-2.5 mm, based on disease phenotype.

Discussion: Integrating IUS with clinical symptoms during routine clinic visits was superior to shPCDAI alone in predicting CD activity, and may potentially be superior to PUCAI for UC. Incorporating IUS into routine visits may accelerate treatment decisions, thereby advancing an improved point-of-care treat-to-target approach.

Background: Corticosteroids have been fundamental in the management of ulcerative colitis (UC) flares, yet many patients do not respond or become corticosteroid dependent. The evolution of this clinical response across successive treatment courses remains underexplored. In this study we aimed to analyze the dynamics of the corticosteroid response over time and identify associated factors.

Methods: We conducted a retrospective cohort study including adult patients with UC diagnosed between 1975 and 2023 and treated with  ≥2 corticosteroid courses. The treatment response was defined by Partial Mayo Score (PMS) criteria. Transitions between response states across courses were modeled using a Markov approach to estimate probabilities and identify factors associated with response.

Results: Of 571 patients with UC, 201 (35.2%) had received ≥2 corticosteroid courses and were included in the study. Over a -median follow-up of 9.8 years (IQR, 6.4-21.3 years) there were 899 corticosteroid courses (708 [78.8%] with prednisone). During follow-up, 89 patients (44.3%) experienced nonresponse at some point and 84 (41.8%) developed steroid dependence. The probability of maintaining a "non-responsive" status through corticosteroid courses was 37.8% (95% CI, 29.6%-46.8%), while complete response persistence was 79.5% (95% CI, 75.5%-82.9%). Intercurrent enteric infections were identified in 23 (11.4%) patients and were associated with corticosteroid non-response within that flare. Beclomethasone use was associated with non-response in the first cycle compared to prednisone (odds ratio [OR], 8.70; 95% CI, 3.65-20.71). The presence of extraintestinal manifestations (OR, 5.34; 95% CI, 1.39-20.45) and greater disease extension (OR, 1.57; 95% CI, 1.05-2.35) were predictors of complete response to corticosteroids through corticosteroid courses.

Conclusions: Corticosteroid response in UC is a dynamic phenomenon. Over a third of non-responders remain unresponsive in subsequent courses. Extraintestinal manifestations, corticosteroid type, and greater disease extension are associated with an increased likelihood of clinical response to corticosteroids.

Background: Perianal manifestations are common at diagnosis of Crohn's Disease and include perianal fistulas, abscesses, fissures, and inflammatory anal skin tags. Perianal fistulizing Crohn's disease (PFCD), involving fistulas and abscesses, is associated with a poor prognosis in children.This study aimed to identify the factors associated with PFCD at diagnosis. Secondary aims were to: assess factors associated with the severity of PFCD according to the Van Assche score, characterize the prevalence of perianal Crohn's disease in a Canadian cohort, and evaluate its management at diagnosis.

Methods: We collected data from patients aged 4-18 years diagnosed with Crohn's disease between 2009 and 2021 at our IBD center who underwent perineal magnetic resonance imaging within three months of diagnosis. Perianal Crohn's disease was assessed clinically and through MRI results.

Results: Among 489 patients (57.9% male, median age 13.8 years), 229 (46.8%) had perianal Crohn's disease. Perianal fistulizing Crohn's disease was identified in 115 patients (23.5%), including 13.0% without any clinical signs. The median Van Assche score was 13.0 in patients with PFCD versus 2.0 in those without. Male sex, granulomas on intestinal biopsies, and anal fissures were associated with both the presence and increased severity of PFCD.

Conclusion: This study emphasizes the importance of performing perianal MRI early at the diagnosis as occult perianal fistulizing Crohn's disease may be discovered. Male sex, granulomas on intestinal biopsies and anal fissures were associated both with the presence of PFCD and increased severity.

Background: Very early-onset inflammatory bowel disease (VEOIBD) (diagnosed under 6 years of age) has attracted considerable attention in recent years, with monogenic forms providing insight into immune dysregulation. However, the majority of VEOIBD patients have a classical polygenic phenotype and a similar disease course to older children.

Methods: The study sought to assess the incidence trends of VEOIBD in Scotland from 1981 to 2014 and to describe the natural history, phenotype, and treatment burden of VEOIBD in a regional cohort from South-East Scotland (1997-2021).

Results: Nationally, 128 (8.1%) of 1567 incident pediatric inflammatory bowel disease (IBD) patients (<16 years of age at diagnosis) were VEOIBD; 10 (8%) of 128 were diagnosed <2 years of age. The incidence of VEOIBD rose from 0.64 per 100 000 per year (1981-1985) to 2.73 per 100 000 per year (2011-2014) (P = .002), an incidence rate ratio of 4.3 (95% confidence interval, 2.4-8.3). The average annual percentage change was 3.9% (95% confidence interval, 2.1%-5.7%) (P < .05). Crohn's disease was the most common subtype (63%); the median age at diagnosis was 4.4 years. The regional cohort (n = 46) had a median follow-up of 11.9 years. Crohn's disease cases presented with isolated colonic involvement in 47%, with pancolitis present in 64% of ulcerative colitis cases. Treatment exposures included immunosuppression (76%), corticosteroids (67%), and anti-tumor necrosis factor therapies (50%). A total of 11% were on no IBD-specific therapy at last follow-up, 11% required surgery and no patient had a diagnosis of monogenic IBD, cancer, or death.

Conclusions: Scotland has a high incidence of VEOIBD, with monogenic IBD exceptionally rare. Although VEOIBD disease burden is high, treatment outcomes are broadly similar to those diagnosed later in childhood based on previous studies.

Background: Remote healthcare aims to improve the management of inflammatory bowel disease (IBD) patients by reducing hospital visits. This is the first study to assess capillary blood sampling at home for routine measurement of chemistry parameters and complete blood count parameters at several time points for disease monitoring in IBD patients.

Methods: In this prospective, single-center proof-of-concept study, 27 patients with Crohn's disease or ulcerative colitis and an indication for frequent blood monitoring performed capillary blood sampling in the hospital (time point 0 [T0]) and at 2 time points at home (T1 and T2). A successful at home sampling was defined as a blood sample that was (1) transported in <48 hours, (2) of sufficient quality, and (3) a sufficient volume.

Results: A total of 21 patients completed the study (mean age 31 years; 69% Crohn's disease, 31% ulcerative colitis). Seventeen (81%) out of 21 and 20 (95%) out of 21 blood samples were successfully analyzed, at T1 (between 2 and 6 weeks after T0) and T2 (between 6 and 12 weeks after T0), respectively. At T2, 12 (57%) out of 21 patients preferred capillary blood sampling at home over venous sampling at the hospital. Younger patients expressed higher satisfaction rates. Fifteen (71%) out of 21 patients reported a better performance with blood sampling at T2 compared with T1.

Conclusions: This study shows a high success rate for capillary blood sampling at home for routine disease monitoring in IBD patients. Device optimization and identification of patient preferences are needed to effectively integrate blood sampling at home in remote monitoring of IBD patients.