scholarly journals P302 Diagnostic accuracy of a serum-based biomarker panel for endoscopic activity in ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S304-S304
Author(s):  
A HOLMER ◽  
B Boland ◽  
S Singh ◽  
H Le ◽  
J Neill ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Diagnostic Accuracy ◽  
Operating Characteristic ◽  
Mucosal Inflammation ◽  
Serum Samples ◽  
Receiver Operating Characteristic Curves ◽  
Biomarker Panel ◽  
Endoscopic Remission

Abstract Background The endoscopic healing index (EHI, Monitr, Prometheus Biosciences, San Diego, CA) is a serum-based biomarker panel available for identifying mucosal inflammation in Crohn’s disease.[1] We aimed to study its performance for identifying mucosal inflammation in ulcerative colitis. Methods EHI was analysed on serum samples paired with endoscopies from adult patients (≥18 years) participating in a prospective biobank (June 2014 to December 2017). Area under receiver operating characteristic curves (AUROC) were used to assess the accuracy of EHI for endoscopic improvement (EI; Mayo endoscopic sub-score [MES] 0–1) and endoscopic remission (ER; MES 0). Sensitivity for EHI was calculated using a cut-off previously identified for Crohn’s disease which optimised performance for ruling out endoscopic activity (20 points). Alternative cut-offs were explored. Results A total of 114 patients were included, with an overall prevalence of 56% and 44% for EI and ER. The AUROC was 0.79 (95% CI 0.70–0.87) for EI and 0.70 (95% CI 0.61–0.80) for ER. A cut-off of 20 points had a sensitivity of 94% (95% CI 83–99%) for ruling out moderate to severe (MES 2–3) endoscopic activity, and a sensitivity of 84% (95% CI 72–92%) for ruling out mild to severe (MES 1–3) endoscopic activity. A cut off of 40 points or higher had > 90% specificity for ruling in moderate to severe (MES 2–3) or mild to severe (MES 1–3) endoscopic activity. (Table 1) Conclusion EHI has favourable accuracy in identifying the presence of mucosal inflammation in patients with ulcerative colitis. Although it was not developed and validated for ulcerative colitis, further validation is warranted. Reference

scholarly journals P281 A serum biomarker panel can accurately identify the presence of mucosal ulcers in patients with Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S292-S293
Author(s):  
A HOLMER ◽  
B Boland ◽  
S Singh ◽  
J Neill ◽  
H Le ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mucosal Inflammation ◽  
Routine Practice ◽  
Operating Characteristics ◽  
Serum Samples ◽  
Ulcer Size ◽  
Biomarker Panel ◽  
Disease Characteristics ◽  
Point Increase

Abstract Background Ulcer healing is the primary endoscopic treatment target in Crohn’s disease (CD) in routine practice. A novel serum-based biomarker panel named endoscopic healing index (EHI, Monitr, Prometheus Biosciences, San Diego, CA) was developed and validated for identifying mucosal inflammation as assessed by the simple endoscopic score for CD (SES-CD).1 We aimed to define the operating characteristics of EHI in routine practice for mucosal ulcers specifically. Methods EHI was analysed on serum samples paired with endoscopies from adult patients (≥18 years) participating in a prospective biobank (June 2014 to December 2018). Patients with an ileal pouch-anal anastomosis or an ileostomy were excluded. The performance of EHI for endoscopic disease activity was evaluated for subcomponents of SES-CD scores (0–60) including ulcer presence and size, extent of ulcerated surface, extent of affected surface, and presence of strictures. Diagnostic performance was assessed using previously identified cut-offs for optimal EHI performance in CD for ruling out endoscopic activity (20 points) and ruling in endoscopic activity (50 points). Logistic regression was performed to identify confounders of EHI (patient factors, disease characteristics) and for the strength of association between EHI and ulcers (presence, size). Results A total of 205 CD patients were included in the analysis (50% male, median age 37 years). EHI values were significantly higher with increasing ulcer size (p < 0.001). An EHI cut-off of 20 points exhibited modest sensitivity for ruling out any ulcers (85%, 95% CI 77–91), and large (0.5–20 mm) or very large (>20 mm) ulcers specifically (92%, 95% CI 84–97). An EHI cut-off of 50 points had modest specificity for ruling in the presence of any ulcers (85%, 95% CI 76–92), and large or very large ulcers specifically (87%, 95% CI 79–92). After accounting for the total extent of inflamed mucosa, extent of strictured mucosa, and disease location, each 20-point increase in EHI was independently associated with an incremental 1.7-fold increased probability for the presence of a large or very large ulcer (aOR 1.7, 95% CI 1.1–2.6). Conclusion EHI values were associated with ulcer size independent of inflammatory or stricture burden, and accurately identified the presence of ulcers and large or very large ulcers specifically. A cut-off of 50 points can reliably rule in the presence of ulcers and allow for treatment adjustment without endoscopy. A cut-off of 20 points can reliably rule out the presence of ulcers and signal completion of treatment adjustment algorithms. Reference

Identification of Target Golimumab Levels in Maintenance Therapy of Crohn’s Disease and Ulcerative Colitis Associated With Mucosal Healing

2019 ◽  
Vol 26 (5) ◽  
pp. 766-773 ◽  
Author(s):  
Karen Boland ◽  
Tomer Greener ◽  
Boyko Kabakchiev ◽  
Joanne Stempak ◽  
Jenna Tessolini ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Operating Characteristic ◽  
Mucosal Healing ◽  
Clinical Practices ◽  
Target Drug ◽  
Endoscopic Remission ◽  
Trough Levels ◽  
Selection Of

Abstract Introduction Golimumab is approved as a therapy for ulcerative colitis (UC) patients. Recent data also demonstrate efficacy in Crohn’s disease (CD); however, little is known about target drug levels to achieve endoscopic remission. Methods We performed a retrospective analysis of IBD patients on maintenance golimumab. Median trough levels were compared using Kruskal-Wallis test, and logistic regression was used to construct a probabilistic model to determine sensitivity and specificity of levels predicting mucosal healing. Results Fifty-eight patients on maintenance golimumab were included (n = 39 CD, n = 19 UC/IBD-unclassified [IBDU]). Forty percent (n = 23) were cotreated with an immunomodulator, 95% (n = 55) of patients were anti-TNF experienced, and 15.5% (n = 9) had 3 or more prior biologic therapies. Forty-four percent of patients achieved mucosal healing with endoscopic response in a further 26% of patients. Clinical remission was recorded in 41% of patients, and 82% had clinical response. Patients were treated with doses generally higher than the approved maintenance dose. In CD patients, median golimumab trough levels were higher in patients with mucosal healing (8.8 μg/mL vs 5.08 μg/mL, P = 0.03). After calculation of a receiver operating characteristic (ROC) curve for mucosal healing vs nonresponse, a trough level >8 μg/mL was associated with mucosal healing, with 67% sensitivity, 88% specificity, and a likelihood ratio of 3:4. Conclusion Treatment with golimumab was associated with mucosal healing in 44% of all IBD patients. Higher golimumab levels were associated with mucosal healing in CD. These findings support the need for prospective studies to determine target golimumab levels in IBD, which may impact current clinical practices in relation to selection of maintenance dosing.

scholarly journals Targeted 1H NMR metabolomics and immunological phenotyping of human fresh blood and serum samples discriminate between healthy individuals and inflammatory bowel disease patients treated with anti-TNF

2021 ◽  
Author(s):  
Sara Notararigo ◽  
Manuel Martín-Pastor ◽  
Juan E. Viñuela Roldán ◽  
Adriano Quiroga ◽  
J. Enrique Dominguez-Munoz ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Clinical Practice ◽  
Crohn's Disease ◽  
T Lymphocyte ◽  
Fresh Blood ◽  
Serum Samples ◽  
Nmr Metabolomics ◽  
Inflammatory Bowel

Abstract Inflammatory bowel disease is a multifactorial etiology, associated with environmental factors that can trigger both debut and relapses. A high level of tumor necrosis factor-α in the gut is the main consequence of immune system imbalance. The aim of treatment is to restore gut homeostasis. In this study, fresh blood and serum samples were used to identify biomarkers and to discriminate between Crohn’s disease and ulcerative colitis patients under remission treated with anti-TNF. Metabolomics based on Nuclear Magnetic Resonance spectroscopy (NMR) was used to detect unique biomarkers for each class of patients. Blood T lymphocyte repertories were characterized, as well as cytokine and transcription factor profiling, to complement the metabolomics data. Higher levels of homoserine-methionine and isobutyrate were identified as biomarkers of Crohn’s disease with ileocolic localization. For ulcerative colitis, lower levels of creatine-creatinine, proline, and tryptophan were found that reflect a deficit in the absorption of essential amino acids in the gut. T lymphocyte phenotyping and its functional profiling revealed that the overall inflammation was lower in Crohn’s disease patients than in those with ulcerative colitis. These results demonstrated that NMR metabolomics could be introduced as a high-throughput evaluation method in routine clinical practice to stratify both types of patients related to their pathology. Key messages NMR metabolomics is a non-invasive tool that could be implemented in the normal clinical practice for IBD to assess beneficial effect of the treatment. NMR metabolomics is a useful tool for precision medicine, in order to sew a specific treatment to a specific group of patients. Finding predictors of response to IFX would be desirable to select patients affected by IBD. Immunological status of inflammations correlates with NMR metabolomics biomarkers.

Predicting endoscopic remission in Crohn’s disease by the modified multiplier SES-CD (MM-SES-CD)

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323799
Author(s):  
Neeraj Narula ◽  
Emily C L Wong ◽  
Jean-Frederic Colombel ◽  
William J Sandborn ◽  
John Kenneth Marshall ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Assessment Tool ◽  
Training Dataset ◽  
Mucosal Inflammation ◽  
Youden Index ◽  
Active Therapy ◽  
Testing Dataset ◽  
Endoscopic Remission

Background and aimsThe Simple Endoscopic Score for Crohn’s disease (SES-CD) is the primary tool for measurement of mucosal inflammation in clinical trials but lacks prognostic potential. We set to develop and validate a modified multiplier of the SES-CD (MM-SES-CD), which takes into consideration each individual parameter’s prognostic value for achieving endoscopic remission (ER) while on active therapy.MethodsIn this posthoc analysis of three CD clinical trial programmes (n=350 patients, baseline SES-CD ≥ 3 with confirmed ulceration), data were pooled and randomly split into a 70% training and 30% testing cohort. The MM-SES-CD was designed using weights for individual parameters as determined by logistic regression modelling, with 1-year ER (SES-CD < 3) being the dependent variable. A cut point score for low and high probability of ER was determined by using the maximum Youden Index and validated in the testing cohort.ResultsBaseline ulcer size, extent of ulceration and presence of non-passable strictures had the strongest association with 1-year ER as compared with affected surface area, with differential weighting of individual parameters across disease segments being observed during logistic regression. The MM-SES-CD was generated using this weighted regression model and demonstrated strong discrimination for ER in the training dataset (area under the receiver operator curve (AUC) 0.83, 95% CI 0.78 to 0.94) and in the testing dataset (AUC 0.82, 95% CI 0.77 to 0.92). In comparison to the MM-SES-CD scoring model, the original SES-CD score lacks accuracy (AUC 0.60, 95% CI 0.55 to 0.65) for predicting the achievement of ER.ConclusionsWe developed and internally validated the MM-SES-CD as an endoscopic severity assessment tool to predict one-year ER in patients with CD on active therapy.

scholarly journals Immunolocalization of leptin and leptin receptor in colorectal mucosa of ulcerative colitis, Crohn’s disease and control subjects with no inflammatory bowel disease

2020 ◽  
Author(s):  
Flavia Merigo ◽  
Alessandro Brandolese ◽  
Sonia Facchin ◽  
Federico Boschi ◽  
Marzia Di Chio ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Lamina Propria ◽  
Leptin Receptor ◽  
Gastrointestinal Symptoms ◽  
Lymphatic Vessels ◽  
Mucosal Inflammation ◽  
Colorectal Mucosa ◽  
Inflammatory Bowel

Abstract The expression of leptin and leptin receptor (Ob-R) has been partially elucidated in colon of patients with inflammatory bowel diseases (IBDs), even though leptin is involved in angiogenesis and inflammation. We previously reported overexpression of GLUT5 fructose transporter, in aberrant clusters of lymphatic vessels in lamina propria of IBD and controls. Here, we examine leptin and Ob-R expression in the same biopsies. Specimens were obtained from patients with ulcerative colitis (UC), Crohn’s disease (CD) and controls who underwent screening for colorectal cancer, follow-up after polypectomy or with a history of lower gastrointestinal symptoms. Immunohistochemistry revealed leptin in apical and basolateral membranes of short epithelial portions, Ob-R on the apical pole of epithelial cells. Leptin and Ob-R were also identified in structures and cells scattered in the lamina propria. In UC, a significant correlation between leptin and Ob-R in the lamina propria was found in all inflamed samples, beyond non-inflamed samples of the proximal tract, while in CD, it was found in inflamed distal samples. Most of the leptin and Ob-R positive areas in the lamina propria were also GLUT5 immunoreactive in inflamed and non-inflamed mucosa. A significant correlation of leptin or Ob-R expression with GLUT5 was observed in the inflamed distal samples from UC. Our findings suggest that there are different sites of leptin and Ob-R expression in large intestine and those in lamina propria do not reflect the status of mucosal inflammation. The co-localization of leptin and/or Ob-R with GLUT5 may indicate concomitance effects in colorectal lamina propria areas.

scholarly journals Serum adipokines as non-invasive biomarkers in Crohn’s disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Lorena Ortega Moreno ◽  
Ancor Sanz-Garcia ◽  
Marina J. Fernández de la Fuente ◽  
Ricardo Arroyo Solera ◽  
Samuel Fernández-Tomé ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Area Under The Curve ◽  
Healthy Controls ◽  
High Concentration ◽  
Serum Samples ◽  
Receiver Operating Characteristic Curves ◽  
Non Invasive ◽  
Healthy Control

Abstract Adipose tissue secretes molecules that can promote activity in Crohn’s disease. We aimed to evaluate the role of serum adipokines as possible biomarkers in Crohn’s disease. Serum samples were obtained from 40 patients with endoscopically active or quiescent Crohn’s disease and 36 healthy controls. Serum leptin, ghrelin, resistin and adiponectin levels were analysed by Multiplex in a Luminex 200 system technology. Receiver Operating Characteristic curves were performed to evaluate the adipokines discriminatory capacity. A logistic regression adjusted by possible confounders (i.e. gender, age, BMI) was performed for those adipokines that showed an area under the curve > 0.7. No differences were found in age, gender or BMI among groups. Distribution for serum resistin was different among the three groups of study, and only this adipokine showed an area under the curve of 0.75 comparing actives patients and healthy control groups. Resistin median concentration was selected as a cut-off for a logistic regression analysis; odds ratio along its 95% confidence interval adjusted by gender, age, and BMI yielded a value of 5.46 (1.34–22.14) comparing actives patients and healthy controls. High concentration of serum resistin is probably associated to activity, being this association independent of gender, age or BMI.

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