Natural History of Pediatric Patients With Crohn’s Disease Treated With Mesalamine Therapy
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ABSTRACT:
SUBMITTER: Young D
PROVIDER: S-EPMC10684219 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
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Project description:Background & aimsLittle is known about the effects of discontinuing mesalamine therapy for patients with Crohn's disease (CD) who initiate therapy with an anti-tumor necrosis factor (anti-TNF) agent. We analyzed data from 2 national population cohorts to compare outcomes of patients with CD already on mesalamine therapy who started treatment with an anti-TNF agent and then either stopped or continued mesalamine.MethodsThe primary outcome was any adverse clinical event, defined as a composite of new corticosteroid use or CD-related hospitalization or surgery. We collected data from the Truven MarketScan (IBM, Armonk, NY) health claims database in the United States and the Danish health registers. Our analysis included patients with CD who started anti-TNF therapy after at least 90 days of oral mesalamine therapy. Patients were classified as stopping mesalamine if therapy was discontinued within 90 days of starting anti-TNF. We performed multivariable Cox regression models controlling for demographics, clinical factors, and health care utilization. Adjusted hazard ratios with 95% CIs were calculated, comparing stopping mesalamine with continuing mesalamine.ResultsA total of 3178 patients with CD were included in our final analysis (2960 in the United States and 218 in Denmark). Stopping mesalamine after initiating anti-TNF therapy was not associated with an increased risk of adverse clinical events in the US cohort (adjusted hazard ratio, 0.89; 95% CI, 0.77-1.03; P = .13) or in the Danish cohort (adjusted hazard ratio, 1.13; 95% CI, 0.68-1.87; P = .63). Similar results were obtained from sensitivity analyses of concomitant immunomodulator use and duration of mesalamine treatment before initiation of anti-TNF therapy.ConclusionsIn a retrospective analysis of 2 national databases, we found that stopping mesalamine therapy for patients with CD who were starting anti-TNF therapy did not increase their risk of adverse clinical events. These results should be validated in a prospective study.
| S-EPMC7015801 | biostudies-literature
Project description:The Relationship between Fecal Bile Acids and Microbiome Community Structure in Pediatric Crohn’s Disease
| PRJEB35587 | ENA
Project description:Previously, we conducted an epigenome-wide study of DNA methylation (~850K sites) in peripheral blood at diagnosis and during follow-up from the RISK pediatric Crohn’s disease inception cohort and data are deposited in GEO with an access number GSE112611. We further followed up this study and identified here the genetic influence on ~850K DNAm sites (mQTL) in peripheral blood as well as newly added 41 ileal biopsies. All the ileal biopsies DNAm data are collected from the subset of primary 238 pediatric CD cohort that contains the peripheral blood DNAm data in GSE112611. Comparing the mQTL effect sizes among 164 CD cases at baseline, 164 CD cases at 3 years follow-up, 74 healthy controls and 41 ileal biopsies confirms that genetic influence on DNAm sites are strongly consistent among these groups. This study further concludes that the mQTLs are largely not disease-specific or inflammation-specific or tissue-specific.
2019-08-17 | GSE135905 | GEO
Project description:Microbial dysbiosis has been suggested to be involved in the pathogenesis of Crohn's disease (CD); however, many studies of gut microbial communities have been confounded by environmental and patient-related factors. In this study, the microbial flora of fecal samples from 19 children newly diagnosed with CD and 21 age-matched controls were analyzed using high-throughput sequencing to determine differences in the microbial composition between CD patients and controls. Analysis of the microbial composition of specific bacterial groups revealed that Firmicutes percentages were significantly lower in CD patients than in controls and that this was due largely to changes in the class Clostridia. Bacteroidetes and Proteobacteria percentages were higher and significantly higher in CD patients than in controls, respectively. Both the detection frequencies of Bacteroidetes and Firmicutes correlated (positively and negatively, respectively) with the calculated pediatric Crohn's disease activity index scores of patients. Upon further analysis, differences in the microbial compositions of patients with mild disease and moderate to severe disease were identified. Our findings indicate that a combination of different bacterial species or a dynamic interplay between individual species is important for disease and is consistent with the dysbiosis hypothesis of CD.
| S-EPMC3457451 | biostudies-literature
Project description:About 40% IBD patients treated with anti-TNF antibodies do not respond to therapy. Baseline biomarkers of response are therefore of interest. By combining computational deconvolution of gene expression and meta-analysis approaches we identified cellular biomarkers in tissue (validated in 2 cohorts by IHC of biopsies), and investigated associated gene biomarkers in blood. This dataset provides data from the validation cohort III (blood).
2018-02-01 | GSE107865 | GEO
Project description:Little is known about the metabolic response of pediatric Crohn's disease (CD) patients to partial enteral nutrition (PEN) therapy and the impact of disease activity and inflammation. We analyzed plasma samples from a nonrandomized controlled intervention study investigating the effect of partial enteral nutrition (PEN) on bone health and growth throughout one year with untargeted metabolomics using high-performance liquid chromatography (HPLC) coupled with high-resolution mass spectrometry (HRMS). Thirty-four paired samples from two time points (baseline and 12 months) were analyzed. Patients (median age: 13.9 years, range: 7-18.9 years, 44% females) were in remission or had mild disease activity. The intervention group received a casein-based formula for 12 months, providing ~25% of estimated daily energy requirements. Sparse partial least squares discriminant analysis (splsda) was applied for group discrimination and identifying sources of variation to identify the impact of PEN. We also investigated the correlation of metabolites with inflammation markers, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fecal calprotectin. After 12 months, our results show substantial difference between PEN and non-PEN groups in the metabolome of CD patients in remission or with mild disease activity. Inflammatory markers were associated with individual compounds and chemical classes such as isoprenoids and phospholipids. Identified compounds comprise metabolites produced by human or bacterial metabolism, as well as xenobiotics recognized as flavoring agents and environmental contaminants and their biotransformation products. Further longitudinal studies that also include patients with higher disease activity are warranted to evaluate the suitability of these metabolic biomarkers for predicting disease activity.
| S-EPMC7985853 | biostudies-literature
Project description:Background and aims5-aminosalicylates (5-ASA) are frequently used in the management of Crohn's disease (CD). We used a de-identified administrative claims database to compare patterns and outcomes of continuing versus stopping 5-ASA in patients with CD who escalated to anti-metabolite monotherapy.MethodsPatients with CD on 5-ASA who were new users of anti-metabolite monotherapy and followed for at least 12 months from OptumLabs® Data Warehouse. Three patterns of 5-ASA use were identified: stopped 5-ASA, short-term 5-ASA (use for < 6 months after starting anti-metabolites), or persistent 5-ASA (use for > 6 months after starting anti-metabolites). Outcomes (need for corticosteroids, risk of CD-related hospitalization and/or surgery, treatment escalation to biologic therapy) were compared using Cox proportional hazard analysis adjusting for key covariates, with a 12-month immortal time period.ResultsOf 3036 patients with CD who were new-users of anti-metabolite monotherapy, 667 (21.9%), 626 (20.6%), and 1743 (57.4%) stopped 5-ASA, used 5-ASA transiently or persistently, respectively. Compared to patients who stopped 5-ASA after starting anti-metabolites, persistent 5-ASA use was associated with a higher risk of corticosteroid use (HR, 1.24 [1.08-1.42]), without an increase in risk of CD-related hospitalization (HR, 1.21 [0.98-1.49]), CD-related surgery (HR, 1.28 [0.90-1.80]) or treatment escalation (HR, 0.85 [0.62-1.20]). Sensitivity analyses using a 3-month window after initiation of anti-metabolites to classify patients as continuing vs. stopping 5-ASA showed similar results. Residual confounding by disease severity could not be excluded.Conclusion5-ASAs are frequently continued long-term even after escalation to anti-metabolite therapy in patients with CD but offer no clinical benefit over stopping 5-ASA.
| S-EPMC9117569 | biostudies-literature
Project description:This study aimed to identify a biomarker predicting response to ustekinumab therapy. Therefore, we used transcriptomic data (colonic and ileal tissue, CD4 T-cell and CD14 monocytes), which we integrated through Multi-Omics Factor Analysis.
2023-10-31 | E-MTAB-7799 | biostudies-arrayexpress
Project description:ObjectivesCurrently, there is no consensus on how to score Crohn's disease (CD) activity assessed by intestinal-ultrasound (IUS) in children. This study aimed to design an easy-to-use IUS score for disease activity in pediatric CD.MethodsChildren undergoing ileo-colonoscopy for CD assessment underwent IUS the day before ileo-colonoscopy, assessed with simple endoscopic score for CD (SES-CD). IUS features were compared to the SES-CD on segmental level. Multiple regression analyses, separately for terminal ileum (TI) and colon, were done to assess predictors of disease activity and to develop a model.ResultsIn 74 CD patients (median 15 years, 48% female), 67 TI and 364 colon segments were assessed. Based on ROC-curves, bowel wall thickness (BWT) was categorized into low (1point: 2-3 mm (TI), 1.6-2 mm (colon)), medium (2points: 3.0-3.7 mm (TI) and 2.0-2.7 mm (colon)) and high (3points: >3.7 mm (TI) and >2.7 mm (colon)). In TI, only BWT was retained in the model (high BWT:OR 11.50, p<0.001). In colon, BWT (high BWT:OR 8.63, p<0.001) and mesenteric fat (1point. OR:3.02, p<0.001) were independent predictors. A PCD-US cut-off of 1 resulted in a sensitivity of 82% (95%CI: 65-93%) and 85% (95% CI 80-89%) and a cut-off of 3 in a specificity of 88% (72-97%) and 92% (87-96%) for TI and colon, respectively. Inter-observer agreement was moderate for TI and colon (K:0.42, K:0.49, respectively).ConclusionsThe PCD-US score is an easy-to-use and reliable score to detect or rule out CD activity on segmental level in children. External validation is needed before applying this score in clinical practice.
| S-EPMC10097488 | biostudies-literature
Project description:Subarachnoid neurocysticercosis (SUBNCC) is usually caused by an aberrant proliferative form of Taenia solium causing mass effect and arachnoiditis. Thirty of 34 SUBNCC patients were treated with extended cysticidal and anti-inflammatory regimens and followed up a median of 4.2 years posttreatment (range: 15 for ≥ 4 years, 20 ≥ 2 years, 26 > 1 year, and 3 < 1 year). The median ages at the time of first symptom, diagnosis, and enrollment were 29.7, 35.6, and 37.9 years, respectively; 58.8% were male and 82.4% were Hispanic. The median time from immigration to symptoms (minimum incubation) was 10 years and the estimated true incubation period considerably greater. Fifty percent also had other forms of NCC. Common complications were hydrocephalus (56%), shunt placement (41%), infarcts (18%), and symptomatic spinal disease (15%). Thirty patients (88.2%) required prolonged treatment with albendazole (88.2%, median 0.55 year) and/or praziquantel (61.8%; median 0.96 year), corticosteroids (88.2%, median 1.09 years), methotrexate (50%, median 1.37 years), and etanercept (34.2%, median 0.81 year), which led to sustained inactive disease in 29/30 (96.7%) patients. Three were treated successfully for recurrences and one has continuing infection. Normalization of cerebral spinal fluid parameters and cestode antigen levels guided treatment decisions. All 15 patients with undetectable cestode antigen values have sustained inactive disease. There were no deaths and moderate morbidity posttreatment. Corticosteroid-related side effects were common, avascular necrosis of joints being the most serious (8/33, 24.2%). Prolonged cysticidal treatment and effective control of inflammation led to good clinical outcomes and sustained inactive disease which is likely curative.
| S-EPMC6947806 | biostudies-literature