Journal of Crohn's & colitis最新文献

Background and aims: Our objective was to compare the efficacy of novel biologics (like vedolizumab and ustekinumab), anti-tumour necrosis factor agents (anti-TNFs), and immunomodulators (IMMs) in preventing postoperative recurrence (POR) of Crohn's disease (CD).

Methods: We searched PubMed, Embase, and the Cochrane Library databases up to December 2023 to identify placebo-controlled, no-treatment-comparison, or positive-controlled studies for the prevention of POR in CD. Endoscopic and clinical recurrence were the primary and secondary endpoint for the efficacy assessment. We conducted traditional direct and Bayesian network meta-analyses to evaluate the preventive effects of selected drugs. Additionally, we ranked interventions based on their scores under the Surface Under the Cumulative Ranking curve (SUCRA).

Results: A total of 17 studies involving 2786 patients were included. In the direct meta-analysis, anti-TNFs, vedolizumab, and IMMs showed greater efficacy in preventing endoscopic POR, compared to controls (placebo or no treatment). When it came to preventing clinical POR, anti-TNFs and IMMs outperformed controls. The network meta-analysis revealed that the risk of endoscopic POR was considerably lower in patients receiving anti-TNFs, vedolizumab, and ustekinumab compared to controls. Regarding the reduction of clinical POR, only anti-TNFs showed significant efficacy compared to controls. Vedolizumab and anti-TNFs were ranked as the most effective strategies in preventing endoscopic and clinical recurrence, respectively.

Conclusions: According to direct and network meta-analysis, in CD patients after surgical resection, novel biologics, especially vedolizumab, were quite effective in decreasing the risk of endoscopic POR, whereas anti-TNFs appeared to perform best in reducing the risk of clinical POR.

Background and aims: Corticosteroids are widely used in managing inflammatory bowel disease [IBD]. While adverse events [AEs] of corticosteroids are well recognised, current understanding of corticosteroid-related AE burden in IBD remains incomplete.

Methods: AE reports for prednisone/prednisolone and budesonide were extracted from the Food and Drug Administration Adverse Event Reporting System [FAERS] and VigiBase databases. Total and frequently reported AEs were tabulated, and AEs of special interest were compared with reports for all drugs using proportional reporting ratio criteria. Database reports were compared with AEs reported in a patient survey capturing corticosteroid exposure and AE recall.

Results: In FAERS and VigiBase, 344,140 and 42,836 AEs were reported, respectively, in patients with IBD; among these, 10,157 [3.0%] and 11,391 [26.6%], respectively, were related to prednisone/prednisolone or budesonide. AEs associated with corticosteroid use in IBD increased over time. Adrenal insufficiency, Cushingoid complications, osteonecrosis, osteoporosis, diabetes and pancreatitis were disproportionately reported for corticosteroids. Among 9229 patients who responded to the survey, 6434 [69.7%] reported corticosteroid exposure. AEs were more frequently recalled by patients exposed to prednisone [61.9%] vs budesonide [27.4%; p = 0.0001]. The most commonly recalled AEs differed from those reported in the pharmacovigilance databases and included weight gain, sleep problems, mood disturbance and skin changes. Younger patients and those with mental health disorders were more likely to recall suicidal thoughts/attempts.

Conclusions: AEs associated with IBD-related corticosteroid use were frequent. Patients reported AEs affecting quality of life, while clinicians disproportionately reported AEs based on objective diagnostic criteria.

Background and aims: Microbiota transplant therapy is an emerging treatment for ulcerative colitis. One proposed mechanism for the benefit of microbiota transplant therapy is through engraftment of donor microbiota. However, the kinetics of engraftment are unknown. We identified SourceTracker as an efficient method both to determine engraftment and for the kinetic study of engrafting donor taxa to aid in determining the mechanism of how this therapy may treat ulcerative colitis.

Methods: Ulcerative colitis patients were treated with either encapsulated (drug name MTP-101C) or placebo capsules daily for eight weeks followed by a four-week washout period. Amplicon sequence data from donors and patients were analyzed using the Bayesian algorithm SourceTracker.

Results: Twenty-seven patients were enrolled, 14 to the placebo group and 13 to the microbiota transplant therapy group. Baseline Shannon and Chao1 indices negatively correlated with week 12 donor engraftment for patients treated with active drug capsules but not for placebo patients. SourceTracker engraftment positively correlated with the week 12 distance from donors measured using the Bray-Curtis similarity metric in treated patients but not with placebo. We identified engrafting taxa from donors in our patients as well as quantified the proportion of donor similarity or engraftment during weeks one through eight (active treatment) and week 12, four weeks after the last dose.

Conclusion: SourceTracker can be used as a simple and reliable method to quantify donor microbial community engraftment and donor taxa contribution in patients with ulcerative colitis and other inflammatory conditions treated with microbiota transplant therapy.

Background: Fecal microbiota transplantation (FMT) is an experimental treatment for ulcerative colitis (UC). We aimed to study microbial families associated with FMT treatment success.

Methods: We analyzed stools from 24 UC patients treated with four FMTs weekly after randomization for pretreatment during three weeks with budesonide (n = 12) or placebo (n = 12). Stool samples were collected nine times pre-, during, and post FMT. Clinical and endoscopic response was assessed 14 weeks after initiation of the study using the full Mayo score. Early withdrawal due to worsening of UC symptoms was classified as non-response.

Results: Nine patients (38%) reached remission at week 14, and 15 patients had a partial response or non-response at or before week 14. With a Dirichlet Multinomial Mixture model we identified five distinct clusters based on the microbiota composition of 180 longitudinally collected patient samples and 27 donor samples. A Prevotellaceae-dominant cluster was associated with poor response to FMT treatment. Conversely, the families Ruminococcaceae and Lachnospiraceae were associated with a successful clinical response. These associations were already visible at the start of the treatment for a subgroup of patients and were retained in repeated measures analyses of family-specific abundance over time. Responders were also characterized by a significantly lower Simpson dominance compared to non-responders.

Conclusions: The success of FMT treatment of UC patients appears to be associated with specific gut microbiota families, such as control of Prevotellaceae. Monitoring the dynamics of these microbial families could potentially be used to inform treatment success early during FMT.

Background: The management of inflammatory bowel disease [IBD] patients with concurrent liver transplantation is challenging, and data regarding the safety and efficacy of Janus kinase [JAK] inhibitors with anti-rejection medications are required. We report the experience of all liver transplant recipients receiving tofacitinib and/or upadacitinib for IBD across three states in Australia.

Methods: All liver transplant recipients from the Australian states of Victoria, New South Wales, and Tasmania, who required tofacitinib or upadacitinib for the treatment of IBD, were identified using prospectively maintained liver transplant databases. Patients were followed up until medication cessation or last follow-up. Clinical safety and efficacy data were collected.

Results: Eight patients [median age 30 years] were included, seven of whom received first-line JAK inhibition with tofacitinib. All patients had failed one or more biologic therapies prior to commencing JAK inhibition, including six patients who had failed two or more agents. JAK inhibition was continued for a median of 17 months, with 143 patient-months of combined follow-up. The anti-rejection medication tacrolimus was prescribed in all patients. Overall, seven [88%] patients achieved clinical remission, including all three patients who were switched from tofacitinib to upadacitinib. One patient required colectomy after 1 month of treatment. There were no other cases of serious infection, venous thromboembolism, or major adverse cardiovascular events during follow-up.

Conclusions: As the largest case series to date, these data indicate that combining JAK inhibition with transplant anti-rejection medication may be a safe and clinically effective method of treating IBD in patients with prior biologic failure.

Background and aims: Psychological symptoms are associated with poorer ulcerative colitis [UC]-related outcomes. However, the majority of research is cross-sectional. We aimed to identify subgroups based on the longitudinal evolution of GI symptom levels and health-related quality of life [HRQoL], and to disentangle the directionality of effects between GI symptom levels and psychological distress.

Methods: Self-reported gastrointestinal [GI] symptom severity, HRQoL, inflammatory biomarkers, and psychological distress were assessed in 98 newly diagnosed UC patients at disease onset and yearly for 3 consecutive years. Latent class growth analysis was used to determine subgroups based on longitudinal trajectories of symptom severity and HRQoL, and baseline predictors of trajectory group membership were determined. Cross-lagged structural equation models were used to disentangle temporal relationships between psychological functioning and symptom severity.

Results: Patients with higher initial psychological distress had increased probability of maintaining higher levels of diarrhoea and abdominal pain. Conversely, patients with lower initial levels of diarrhoea and abdominal pain had higher chances of maintaining lower levels of psychological distress. Higher levels of C-reactive protein at baseline predicted greater improvements in mental health after anti-inflammatory treatment. Reductions in diarrhoea and abdominal pain preceded reductions in psychological symptoms over time.

Conclusions: Baseline psychological distress is predictive of increased GI symptom severity and reduced mental HRQoL over time, suggesting early assessment of psychological symptoms may identify patients who may have worse disease trajectories. Abdominal pain predicted increased psychological distress, but not the other way around. Intervening on abdominal pain may help prevent or reduce future psychological distress.

Magnetic resonance enterography [MRE] and intestinal ultrasound [IUS] have developed rapidly in the past few decades, emerging as the primary non-invasive options for both diagnosing and monitoring Crohn's disease [CD]. In this review, we evaluate the pertinent data relating to the use of MRE and IUS in CD. We summarise the key imaging features of CD activity, highlight their increasing role in both the clinical and the research settings, and discuss how these modalities fit within the diagnostic pathway. We discuss how they can be used to assess disease activity and treatment responsiveness, including the emergence of activity scores for standardised reporting. Additionally, we address areas of controversy such as the use of contrast agents, the role of diffusion-weighted imaging, and point-of-care ultrasound. We also highlight exciting new developments, including the applications of artificial intelligence. Finally, we provide suggestions for future research priorities.