scholarly journals Ranking microbiome variance in inflammatory bowel disease: a large longitudinal intercontinental study

Gut ◽  
2020 ◽  
pp. gutjnl-2020-321106 ◽  
Author(s):  
Adam G Clooney ◽  
Julia Eckenberger ◽  
Emilio Laserna-Mendieta ◽  
Kathryn A Sexton ◽  
Matthew T Bernstein ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Rational Design ◽  
Geographic Location ◽  
16S Rrna Gene Sequencing ◽  
Inactive Disease ◽  
Rrna Gene ◽  
Time Points ◽  
Inflammatory Bowel

ObjectiveThe microbiome contributes to the pathogenesis of inflammatory bowel disease (IBD) but the relative contribution of different lifestyle and environmental factors to the compositional variability of the gut microbiota is unclear.DesignHere, we rank the size effect of disease activity, medications, diet and geographic location of the faecal microbiota composition (16S rRNA gene sequencing) in patients with Crohn’s disease (CD; n=303), ulcerative colitis (UC; n = 228) and controls (n=161), followed longitudinally (at three time points with 16 weeks intervals).ResultsReduced microbiota diversity but increased variability was confirmed in CD and UC compared with controls. Significant compositional differences between diseases, particularly CD, and controls were evident. Longitudinal analyses revealed reduced temporal microbiota stability in IBD, particularly in patients with changes in disease activity. Machine learning separated disease from controls, and active from inactive disease, when consecutive time points were modelled. Geographic location accounted for most of the microbiota variance, second to the presence or absence of CD, followed by history of surgical resection, alcohol consumption and UC diagnosis, medications and diet with most (90.3%) of the compositional variance stochastic or unexplained.ConclusionThe popular concept of precision medicine and rational design of any therapeutic manipulation of the microbiota will have to contend not only with the heterogeneity of the host response, but also with widely differing lifestyles and with much variance still unaccounted for.

scholarly journals P60 Efficacy of switching to infliximab biosimilar (Remsima®) in paediatric inflammatory bowel disease (PIBD): a 2-Year retrospective evaluation

2020 ◽  
Vol 105 (9) ◽  
pp. e37.2-e38
Author(s):  
Fatima Yaqub ◽  
Joanne Crook ◽  
John Fell
Keyword(s):  
Inflammatory Bowel Disease ◽  
Treatment Failure ◽  
Disease Activity ◽  
Patient Outcomes ◽  
Bowel Disease ◽  
Adverse Reactions ◽  
Double Blind ◽  
Time Points ◽  
Parallel Group ◽  
Inflammatory Bowel

AimTo evaluate patient outcomes 2 years post switching Infliximab therapy from Infliximab originator molecule Remicade® to biosimilar Remsima®.MethodsPatients with PIBD who experienced induction with Remicade® therapy, were <18 years old at last follow-up and were receiving active treatment with Remsima® 2 years post switching were selected to be included for evaluation. Outcome measures included monitoring disease activity and treatment failure at baseline (before switching) and at selected time points up to 2 years post-switch. Disease activity was assessed looking at a range of parameters: disease activity scores; trough infliximab levels; haematological markers (HGB, platelets, WBC); LFTs (bilirubin, ALT, ALP); inflammatory markers (ESR, CRP) and faecal calprotectin levels. Patients who failed therapy were assessed for adverse reactions and infliximab antibody formation. Data was analysed with the Cochran Q test, repeated measures ANOVA test and Friedman test; with post-hoc Bonferroni and Wilcoxon Signed-Ranks tests if appropriate.ResultsData was available for 18 patients after exclusion criteria were applied. There was a significant increase in trough infliximab levels by the end of the period from an average of 5 ug/L to 12 ug/L at 2 years. The average dose/kg increased over 2 years by 1.5 mg/kg. Disease activity markers showed no changes between time points except a decrease in ALP levels from baseline to 1 year, but values remained within normal ranges. Four patients were discontinued from Remsima® due to side effects or loss of efficacy. The average time to treatment failure on Remsima® was 38 months (~19/20 doses). Three out of four patients developed infliximab antibodies, 2 of these patients went on to suffer adverse reactions; 1 exhibited joint pain which settled weeks after each infusion and the other developed an immediate infusion reaction in the form of a rash with urticaria on the 3rd infusion of Remsima®.ConclusionInfliximab biosimilars, such as Remsima®, were approved for use in PIBD by the EMA after studies in adult populations with rheumatic diseases.1 2 Induction studies have shown efficacy in PIBD but data on switching is limited and short-term.3 4 Our data shows no significant differences in clinical patient outcomes over a 2-year period in a cohort switched from Remicade® to Remsima®. In fact, a significant increase in trough infliximab levels in patients remaining on Remsima® suggests efficacy in producing therapeutic levels in PIBD patients. Increased levels may be explained by dose intensification used by the PIBD multi-disciplinary team (MDT), reflecting careful dose optimisation strategies used at this trust throughout the time period. Patients losing response were not unexpected and are likely not due to the biosimilar switch but rather due to the length of time the patients were on treatment. The small sample size and retrospective nature of this study mean larger cohort studies are required over prolonged time periods to confirm these findings. PIBD MDTs should continue to monitor patients for adverse reactions, particularly in those who develop infliximab antibodies.ReferencesPark W, Hrycaj P, Jeka S, et al. A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study. Ann Rheum Dis 2013;72:1605–1612.Yoo DH, Hrycaj P, Miranda P, et al. Extended report: a randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when co-administered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study. Ann Rheum Dis 2013;72:1613.Sieczkowska J, Jarzębicka D, Banaszkiewicz A, et al. Switching Between Infliximab Originator and Biosimilar in Paediatric Patients with Inflammatory Bowel Disease. Preliminary Observations. J Crohn’s Colitis 2016;10:127–132.Sieczkowska J, Jarzębicka D, Meglicka M, et al. Experience with biosimilar infliximab (CT-P13) in paediatric patients with inflammatory bowel diseases. Therap Adv Gastroenterol 2016;9:729–735.

scholarly journals Evaluation of Serum Leucine-Rich Alpha-2 Glycoprotein as a New Inflammatory Biomarker of Inflammatory Bowel Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Tetsuhiro Yoshimura ◽  
Keiichi Mitsuyama ◽  
Ryosuke Sakemi ◽  
Hidetoshi Takedatsu ◽  
Shinichiro Yoshioka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Mononuclear Cells ◽  
Inflammatory Marker ◽  
Inactive Disease ◽  
Healthy Controls ◽  
Laboratory Parameters ◽  
Inflammatory Bowel

Studies on serum leucine-rich alpha-2 glycoprotein (LRG) in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are scarce; the methods for estimating disease activity are less established, particularly for CD. This study is aimed at evaluating the utility of serum LRG as a potential inflammatory marker for IBD and to investigate the LRG gene expression in peripheral blood mononuclear cells (PBMCs) as a possible source of serum LRG. Overall, 98 patients with UC and 96 patients with CD were prospectively enrolled and clinically evaluated; 92 age-matched individuals served as the healthy controls. The blood samples were analyzed for serum LRG levels and routine laboratory parameters. Disease activity was assessed clinically and endoscopically. Finally, LRG gene expression in the PBMCs from a different cohort (41 patients with UC, 34 patients with CD, and 30 healthy controls) was examined. The serum LRG levels were higher during active disease than during inactive disease; additionally, serum LRG levels were positively correlated with clinical disease activity, C-reactive protein (CRP) levels, and other laboratory parameters in patients with UC and CD and with endoscopic disease activity in UC. UC and CD showed comparable areas under the curve (AUC) values for determining clinical remission and differentiating between endoscopic remission associated with LRG and CRP. The levels of LRG mRNA were also increased in PBMCs from patients with UC and CD and reflected disease activity. These data suggest that serum LRG, originated partially from PBMCs, is an inflammatory marker in UC and CD. A large-scale well-designed study should be conducted in the future to more accurately reveal the clinical significance of LRG in patients with IBD.

scholarly journals High Abundance of Proteobacteria in Ileo-Anal Pouch Anastomosis and Increased Abundance of Fusobacteria Associated with Increased Pouch Inflammation

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 237 ◽  
Author(s):  
Andreas Munk Petersen ◽  
Hengameh Chloé Mirsepasi-Lauridsen ◽  
Marianne K. Vester-Andersen ◽  
Nikolaj Sørensen ◽  
Karen Angeliki Krogfelt ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Activity Index ◽  
Fecal Calprotectin ◽  
Inactive Disease ◽  
E Coli ◽  
Α Diversity ◽  
Inflammatory Bowel

Low diversity intestinal dysbiosis has been associated with inflammatory bowel disease, including patients with ulcerative colitis with an ileo-anal pouch anastomosis. Furthermore, specific Escherichia coli phylogroups have been linked to inflammatory bowel disease. Our aim was to characterize the differences among microbiota and E. coli phylogroups in active and inactive pouchitis. Disease activity was assessed using the modified pouch disease activity index and by fecal calprotectin. Microbiota diversity was assessed by 16S rDNA MiSeq sequencing. E. coli phylogroup was determined after triplex PCR. Twenty patients with ulcerative colitis with an ileo-anal pouch anastomosis were included, 10 of whom had active pouchitis. Ileo-anal pouch anastomosis patients had an increased abundance of Proteobacteria colonization compared to patients with ulcerative colitis or Crohn’s disease and healthy controls, p = 1.4·10−5. No differences in E. coli phylogroup colonization could be determined between cases of active and inactive disease. No significant link was found between α-diversity and pouch inflammation. However, higher levels of Fusobacteria colonization were found in patients with a pouch with a fecal calprotectin level above 500, p = 0.02. In conclusion, patients with a pouch had an increased Proteobacteria abundance, but only Fusobacteria abundance was linked to inflammation.

scholarly journals Long-term safety and effectiveness of etanercept in JIA: an 18-year experience from the BiKeR registry

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Giulia Armaroli ◽  
Ariane Klein ◽  
Gerd Ganser ◽  
Michael J. Ruehlmann ◽  
Frank Dressler ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Continuous Treatment ◽  
Inactive Disease ◽  
Minimal Disease Activity ◽  
Serious Infections ◽  
Inflammatory Bowel ◽  
Minimal Disease

Abstract Background At present, etanercept represents the most commonly prescribed biologic agent for juvenile idiopathic arthritis (JIA) treatment. Children and adolescents with JIA are often treated with etanercept over long periods, sometimes even into adulthood. The objectives of this analysis were to determine the long-term safety of etanercept compared to a biologic-naïve cohort and to assess the long-term treatment response upon continuous etanercept exposure using data from the German biologics registry (BiKeR). Methods JIA patients newly exposed to etanercept were documented in the BiKeR registry from January 2001 to March 2019, and baseline characteristics, effectiveness, and safety parameters were analysed. Response to treatment was assessed according to 10-joint Juvenile Arthritis Disease Activity Score (JADAS10), JADAS-defined minimal disease activity and remission, JIA-American College of Rheumatology (ACR) improvement criteria, and ACR-inactive disease definition. Safety assessments were based on adverse event (AE) reports. Results A total of 2725 new etanercept users with a diagnosis of JIA were registered. Of these, etanercept was received as a first-line biologic by 95.8% and as monotherapy without concomitant methotrexate by 31.5%. After nine years on continuous treatment, 68.1% of patients presented minimal disease activity, 43.1% JADAS-defined remission on drug, and 36.6% ACR-inactive disease. JIA-ACR30/50/70/90 response rates were still 82/79/71/54% after nine years of treatment. Overall, 2053 AEs (34.3/100PY), including 226 serious AEs (SAE, 3.8/100PY), were observed upon etanercept, compared to 1345 AEs [35.6/100PY; p = 0.3] and 52 SAEs (1.4/100PY; p = 0.0001) in the biologic-naïve cohort. Respective exposure-adjusted rates for etanercept and biologic-naïve patients were 0.9/100PY and 0.2/100PY (p = 0.0001) for serious infections, 0.4/100PY and 0.1/100PY (p = 0.01) for zoster reactivation, 0.3/100PY and 0.03/100PY (p = 0.015) for inflammatory bowel disease, and 1.9/100PY and 1.4/100PY (p = 0.09) for uveitis. Three and two malignancies were documented in the etanercept and biologic-naïve groups, as well as three and one deaths, respectively. Conclusions No new safety signal was observed, especially no increased risk for malignancies or autoimmune disorders other than inflammatory bowel disease. However, SAEs and serious infections, though infrequent, were more often reported on etanercept than in biologic-naïve patients. In addition, etanercept demonstrated a long-term maintenance of clinical benefits up to nine years of continuous treatment.

Localization and Activity of Inflammatory Bowel Disease Using 111ln Leukocyte Imaging

1988 ◽  
Vol 27 (03) ◽  
pp. 83-86 ◽  
Author(s):  
B. Briele ◽  
F. Wolf ◽  
H. J. Biersack ◽  
F. F. Knapp ◽  
A. Hotze
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Cell Uptake ◽  
Disease Extent ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Leukocyte Imaging

A prospective study was initiated to compare the clinically proven results concerning localization/extent and activity of inflammatory bowel diseases with those of 111ln-oxine leukocyte imaging. All patients studied were completely examined with barium enema x-ray, clinical and laboratory investigations, and endoscopy with histopathology. A total of 31 leukocyte scans were performed in 15 patients (12 with Crohn’s disease, 3 with ulcerative colitis). The scans were graded by comparing the cell uptake of a lesion (when present) and a bone marrow area providing a count ratio (CR). The inflammatory lesions were correctly localized on 26 leukocyte scans, and in 21 scans the scintigraphically estimated extent of disease was identical to endoscopy. In 5 cases the disease extent was underestimated, 4 scans in patients with relapse of Crohn’s disease were falsely negative, and in one patient with remission truly negative. The scintigraphically assessed disease activity was also in a good agreement with clinical disease activity based on histopathology in all cases. We conclude that leukocyte imaging provides valuable information about localization and activity of inflammatory bowel disease.

scholarly journals Predicting disease course in ulcerative colitis using stool proteins identified through an aptamer-based screen

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sanam Soomro ◽  
Suresh Venkateswaran ◽  
Kamala Vanarsa ◽  
Marwa Kharboutli ◽  
Malavika Nidhi ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Fecal Calprotectin ◽  
Disease Monitoring ◽  
Disease Course ◽  
Lipocalin 2 ◽  
Time Points ◽  
Inflammatory Bowel ◽  
Stool Samples

AbstractIn the search for improved stool biomarkers for inflammatory bowel disease (IBD), an aptamer-based screen of 1129 stool proteins was conducted using stool samples from an IBD cohort. Here we report that of the 20 proteins subsequently validated by ELISA, stool Ferritin, Fibrinogen, Haptoglobin, Hemoglobin, Lipocalin-2, MMP-12, MMP-9, Myeloperoxidase, PGRP-S, Properdin, Resistin, Serpin A4, and TIMP-1 are significantly elevated in both ulcerative colitis (UC) and Crohn’s disease (CD) compared to controls. When tested in a longitudinal cohort of 50 UC patients at 4 time-points, fecal Fibrinogen, MMP-8, PGRP-S, and TIMP-2 show the strongest positive correlation with concurrent PUCAI and PGA scores and are superior to fecal calprotectin. Unlike fecal calprotectin, baseline stool Fibrinogen, MMP-12, PGRP-S, TIMP-1, and TIMP-2 can predict clinical remission at Week-4. Here we show that stool proteins identified using the comprehensive aptamer-based screen are superior to fecal calprotectin alone in disease monitoring and prediction in IBD.

scholarly journals Utility of routinely collected electronic health records data to support effectiveness evaluations in inflammatory bowel disease: a pilot study of tofacitinib

2021 ◽  
Vol 28 (1) ◽  
pp. e100337
Author(s):  
Vivek Ashok Rudrapatna ◽  
Benjamin Scott Glicksberg ◽  
Atul Janardhan Butte
Keyword(s):  
Inflammatory Bowel Disease ◽  
Pilot Study ◽  
Disease Activity ◽  
Real World ◽  
Bowel Disease ◽  
P Value ◽  
Health Records ◽  
Real World Evidence ◽  
Inflammatory Bowel

ObjectivesElectronic health records (EHR) are receiving growing attention from regulators, biopharmaceuticals and payors as a potential source of real-world evidence. However, their suitability for the study of diseases with complex activity measures is unclear. We sought to evaluate the use of EHR data for estimating treatment effectiveness in inflammatory bowel disease (IBD), using tofacitinib as a use case.MethodsRecords from the University of California, San Francisco (6/2012 to 4/2019) were queried to identify tofacitinib-treated IBD patients. Disease activity variables at baseline and follow-up were manually abstracted according to a preregistered protocol. The proportion of patients meeting the endpoints of recent randomised trials in ulcerative colitis (UC) and Crohn’s disease (CD) was assessed.Results86 patients initiated tofacitinib. Baseline characteristics of the real-world and trial cohorts were similar, except for universal failure of tumour necrosis factor inhibitors in the former. 54% (UC) and 62% (CD) of patients had complete capture of disease activity at baseline (month −6 to 0), while only 32% (UC) and 69% (CD) of patients had complete follow-up data (month 2 to 8). Using data imputation, we estimated the proportion achieving the trial primary endpoints as being similar to the published estimates for both UC (16%, p value=0.5) and CD (38%, p-value=0.8).Discussion/ConclusionThis pilot study reproduced trial-based estimates of tofacitinib efficacy despite its use in a different cohort but revealed substantial missingness in routinely collected data. Future work is needed to strengthen EHR data and enable real-world evidence in complex diseases like IBD.

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