Journal of Crohn's & colitis最新文献

Background and aims: To demonstrate that administration of 7500 Trichuris suis ova [TSO] every second week over 24 weeks would reduce the intestinal inflammation in moderate ulcerative colitis.

Methods: A single-centre, randomised, double-blinded, placebo-controlled, phase 2b clinical trial of 7500 Trichuris suis ova every 2 weeks for 24 weeks compared with placebo in moderate activity of ulcerative colitis [Mayo score 6-10] were performed. Primary outcome: clinical remission; secondary outcomes: clinical response at 24 weeks, complete corticosteroid-free clinical remission, endoscopic remission, symptomatic remission at 12 and 24 weeks, and partial Mayo score over time.

Results: In all, 119 patients were randomised to Trichuris suis ova [n = 60] or placebo [n = 59]. At Week 24, clinical remission was achieved in 30% of Trichuris suis ova-treated vs 34% of placebo-treated (risk ratio [RR] = 0.89; 95% confidence interval [CI]: 0.52-1.50; p = 0.80, intention to treat). No difference was found in clinical response in any of the clinical response subgroups. However, in patients who did not need treatment with corticosteroids during the trial, a temporary effect of TSO was seen in the analysis of symptomatic remission at Week 12 [p = 0.01] and the partial Mayo score at Week 14 and Week 18 [p < 0.05 and p = 0.02].

Conclusions: Compared with placebo, Trichuris suis ova administration was not superior in achieving clinical remission at Week 24 in ulcerative colitis or in achieving clinical Mayo score reduction, complete corticosteroid-free clinical remission, or endoscopic remission. However, Trichuris suis ova treatment induced symptomatic temporary remission at Week 12.

Background: Fatigue and psychosocial impairments are highly prevalent in IBD, particularly during active disease. Disturbed brain-gut interactions may contribute to these symptoms. This study examined associations between brain structure, faecal calprotectin, and symptoms of fatigue, depression, and anxiety in persons with Crohn's disease [CD] in different disease states.

Methods: In this prospective observational study, n = 109 participants [n = 67 persons with CD, n = 42 healthy controls] underwent cranial magnetic resonance imaging, provided stool samples for analysis of faecal calprotectin, and completed questionnaires to assess symptoms of fatigue, depression, and anxiety. We analysed differences in grey matter volume [GMV] between patients and controls, and associations between regional GMV alterations, neuropsychiatric symptoms, and faecal calprotectin.

Results: Symptoms of fatigue, depression, and anxiety were increased in patients with CD compared with controls, with highest scores in active CD. Patients exhibited regionally reduced GMV in cortical and subcortical sensorimotor regions, occipitotemporal and medial frontal areas. Regional GMV differences showed a significant negative association with fatigue, but not with depression or anxiety. Subgroup analyses revealed symptom-GMV associations for fatigue in remitted but not in active CD, whereas fatigue was positively associated with faecal calprotectin in active but not in remitted disease.

Conclusion: Our findings support disturbed brain-gut interactions in CD which may be particularly relevant for fatigue during remitted disease. Reduced GMV in the precentral gyrus and other sensorimotor areas could reflect key contributions to fatigue pathophysiology in CD. A sensorimotor model of fatigue in CD could also pave the way for novel treatment approaches.

Introduction: Overall, 30-40% patients with acute severe ulcerative colitis [ASUC] fail intravenous [IV] steroids, requiring medical rescue therapy/colectomy. Low baseline albumin predicts steroid non-response, and exclusive enteral nutrition [EEN] has been shown to improve steroid response and albumin levels. Albumin infusion, due to its anti-inflammatory and antioxidant properties, might further improve steroid response in ASUC, which was evaluated in the present study.

Methods: In this open-label, randomised, controlled trial, patients with ASUC were randomised in 1:1 ratio to either albumin + standard of care [SOC] + EEN [Albumin arm] or SOC + EEN [SOC arm], over January 2021-February 2023. Both arms received 5 days of EEN with 400 mg IV hydrocortisone/day. Patients in the Albumin arm were administered 5 days of 20% weight/volume [w/v] intravenous albumin [100 ml]. Primary outcome was first, steroid failure [need for rescue medical therapy or colectomy] and second, proportion of patients with adverse events.

Results: In all, 61 patients [albumin: 30, SOC: 31][mean age 31.6 ± 0.4 years, male 57.4%], were included. Baseline characteristics were comparable. There was no difference in steroid failure between Albumin and SOC arms (10/30 [33.33%] vs 13/31[41.94%], p = 0.49). No adverse events were reported with albumin infusions. Colectomy rate [10% vs 9.68%, p = 1], response to salvage medical therapy [88.89% vs 76.92%, p = 0.62] and median [interquartile range] duration of hospitalisation [10.5 [7-16] vs 10 [7-20], p = 0.43] were also comparable. The long-term composite outcome of colectomy and re-admission rates was numerically higher in the Albumin than the SOC arm [37.04% vs 17.86%, p > 0.05], although this did not reach statistical significance.

Conclusion: There was no benefit of intravenous albumin infusion as an adjunct to IV steroids and EEN in patients with ASUC.

Background and aims: The effectiveness of transition programs from paediatric to adult healthcare in adolescents with inflammatory bowel disease is not clear, as prospective studies using validated outcome measures for transition are lacking. This study aimed to develop and validate a quantitative Transition Success Score, and to apply it in a multicenter setting to assess the effectiveness of transitional care.

Methods: The Top 10 outcome items related to successful transition, identified through an international Delphi study with IBD stakeholders, were integrated into a generic questionnaire, the Transition Success Score. In a prospective, multicenter study, Transition Success Score was scored by adult healthcare providers, young adult patients and caregivers, 9-15 months after transfer of care.

Results: In seven Dutch hospitals, 160 patients completed the Transition Success Score. The mean score was 25 (range 17-27), 25.6% of patients achieving maximum score. Hypothesis testing for construct validity revealed significant associations with characteristics related to transitional care, such as knowledge, independence, and quality of life (p <0.005). Structural validation indicated the score was most effective at discerning lower levels of transition success. Internal consistency was acceptable (0.64). High disease burden, exacerbation during or after transfer, and certain personality profiles were associated with lower scores.

Conclusions: The Transition Success Score serves as a quantitative tool to evaluate the effectiveness of transitional care interventions and to identify inflammatory bowel disease patients at risk of encountering challenges during the transition to adult healthcare.

Background and aims: Achieving deep remission, encompassing clinical, endoscopic, and biological remission, is the goal in managing Crohn's disease (CD). The role of histological remission remains unclear. This study aimed to examine the impact of histological inflammation on clinical relapse risk in CD and explore the relationship between histology, endoscopic scores, and biomarkers.

Methods: Patients from the prospective STORI cohort underwent ileocolonoscopy with CDEIS calculation and 2 biopsies from the most inflamed or previously inflamed areas. Histological scores (Robarts, Geboes, modified Geboes, Nancy, and IBD-DCA) were determined by two independent pathologists in a central reading process. Histological remission was defined by specific score thresholds. Clinical relapse, defined by CDAI >250 or a CDAI increase of 70 points over two weeks, was monitored for at least one year.

Results: Out of 115 patients included in STORI, 160 biopsies (44 ileal and 116 colonic) from 76 patients were analyzed. Histological remission rates were 46% (Nancy), 55% (Robarts), 61% (Geboes), and 41% (IBD-DCA). During follow-up, 35 patients (46%) experienced a clinical relapse: 37% with histological remission and 56% without, based on the Nancy score. Among the mucosal healing (MH) subgroup (45 patients), 34% with histological remission and 44% without relapsed (p=0.18). Histological scores did not predict clinical relapse. Only faecal calprotectin (FC) was a significant predictor in multivariate analysis (p=0.029).

Conclusion: Despite correlations with endoscopy and biomarkers, histological scores did not predict clinical relapse in CD patients in remission. Thus, these scores are not recommended for clinical practice to assess relapse risk in CD.

Background and aims: Normalization of high-sensitivity C-reactive protein [hs-CRP] and fecal calprotectin [FCP] are suggested Crohn's disease [CD] intermediate treatment targets. This analysis evaluates achievement of biomarker normalization and the relationship between improvements in biomarker concentrations and clinical and endoscopic outcomes among patients treated with risankizumab.

Methods: This post hoc analysis included patients with moderately to severely active CD and elevated baseline hs-CRP [> 5 mg/L] or FCP [> 250 µg/g] concentrations from the 12-week ADVANCE and MOTIVATE induction studies, and the 52-week FORTIFY maintenance study. We assessed the proportion of patients achieving biomarker normalization, defined as hs-CRP ≤ 5 mg/L and FCP ≤ 250 µg/g, and the association between achieving biomarker normalization and improved clinical and endoscopic outcomes.

Results: Among 748 patients with elevated baseline hs-CRP or FCP concentrations, higher proportions of patients treated with risankizumab vs placebo achieved normalization of hs-CRP [week 12: placebo, 17.5%; risankizumab 600 mg, 48.5%; week 52: placebo, 29.5%; risankizumab 180 mg, 45.2%; risankizumab 360 mg, 40.8%] and FCP [week 12: placebo, 9.1%; risankizumab 600 mg, 26.0%; week 52: placebo, 28.0%; risankizumab 180 mg, 43.0%; risankizumab 360 mg, 44.0%; nominal p < 0.05 vs placebo for all comparisons]. Achievement of both clinical or endoscopic outcomes and improvement of biomarker concentrations occurred at higher rates among patients treated with risankizumab vs placebo, regardless of prior exposure to biologic therapies.

Conclusions: Risankizumab treatment led to sustained normalization of inflammatory biomarkers with improved clinical and endoscopic results.

The incidence of inflammatory bowel disease [IBD] is rising most rapidly among children and adolescents. Paediatric-onset IBD is associated with a more extensive and severe disease course compared to adult-onset IBD. At a young age, screening for underlying genetic and immunological disorders is important and may impact treatment management. Early and effective treatment is crucial to reach disease remission and prevent complications of ongoing active disease. In children with Crohn's disease, exclusive enteral nutrition is an effective induction therapy. Other promising dietary therapies, such as the Crohn's disease exclusion diet, are emerging. Within paediatric IBD, anti-tumour necrosis factor therapy is the only approved biological thus far and additional treatment options are crucially needed. Other biological therapies, such as vedolizumab and ustekinumab, are currently prescribed off-label in this population. A specific challenge in paediatric IBD is the unacceptable and major delay in approval of drugs for children with IBD. A guided transfer period of paediatric patients to adult care is associated with improved disease outcomes and is required. Major knowledge gaps and challenges within paediatric IBD include the aetiology, diagnostics, and monitoring of disease, tailoring of treatment, and both understanding and coping with the physical and psychological consequences of living with IBD. Challenges and research gaps in paediatrics should be addressed without any delay in comparison with the adult field, in order to ensure a high quality of care for all patients with IBD, irrespective of the age of onset.

There are growing numbers of older people with inflammatory bowel diseases [IBD]. These older patients are more likely to have other comorbidities and polypharmacy, which can make recognizing and treating IBD complex. Frailty is a newer concept in the IBD field, and we are beginning to recognize the importance of this as a marker of biological age and its association with risk of adverse IBD-related outcomes. In this review article we aim to provide practical insight into the specific challenges facing older patients and their clinicians at each stage of the patient journey. We also discuss the latest understanding of the impact of frailty for these patients with IBD and highlight areas for future research.