scholarly journals Serum MMP-9: a novel biomarker for prediction of clinical relapse in patients with quiescent Crohn’s disease, a post hoc analysis

2019 ◽  
Vol 12 ◽  
pp. 175628481988159 ◽  
Author(s):  
Doron Yablecovitch ◽  
Uri Kopylov ◽  
Adi Lahat ◽  
Michal M. Amitai ◽  
Eyal Klang ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Inflammation ◽  
Area Under The Curve ◽  
Fecal Calprotectin ◽  
Clinical Relapse ◽  
Post Hoc Analysis ◽  
Reactive Protein ◽  
Increased Risk ◽  
Post Hoc

Background: Matrix metalloproteinase-9 (MMP-9) is a novel marker of intestinal inflammation. The aim of this study was to assess if serum MMP-9 levels predict clinical flare in patients with quiescent Crohn’s disease (CD). Methods: This study was a post hoc analysis of a prospective observational study in which quiescent CD patients were included and followed until clinical relapse or the end of a 2-year follow-up period. Serial C-reactive protein (CRP) and fecal calprotectin (FC) levels were measured, and the patients underwent repeated capsule endoscopies (CEs) every 6 months. Small bowel inflammation was quantified by Lewis score (LS) for CE. A baseline magnetic resonance enterography was also performed, and MaRIA score was calculated. Serum MMP-9 levels in baseline blood samples were quantified by ELISA. Results: Out of 58 eligible enrolled patients, 16 had a flare. Higher levels of baseline MMP-9 were found in patients who developed subsequent symptomatic flare compared with patients who did not [median 661 ng/ml, 25–75 interquartile range (IQR; 478.2–1441.3) versus 525.5 ng/ ml (339–662.7), respectively, p = 0.01]. Patients with serum MMP-9 levels of 945 ng/ ml or higher were at increased risk for relapse within 24 months [area under the curve (AUC) of 0.72 [95% confidence interval (CI): 0.56–0.88]; hazard ratio 8.1 (95% CI 3.0–21.9, p < 0.001)]. Serum MMP-9 concentrations showed weak and moderate correlation to baseline LS and FC, respectively ( r = 0.31, p = 0.02; r = 0.46, p < 0.001). No correlation was found between serum MMP-9 to CRP and MaRIA score. Conclusions: Serum MMP-9 may be a promising biomarker for prediction of clinical flare in CD patients with quiescent disease.

scholarly journals Association of Biomarker Cutoffs and Endoscopic Outcomes in Crohn’s Disease: A Post Hoc Analysis From the CALM Study

2020 ◽  
Vol 26 (10) ◽  
pp. 1562-1571 ◽  
Author(s):  
Walter Reinisch ◽  
Remo Panaccione ◽  
Peter Bossuyt ◽  
Filip Baert ◽  
Alessandro Armuzzi ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Surrogate Marker ◽  
Fecal Calprotectin ◽  
Sensitivity Analyses ◽  
End Points ◽  
Predictive Values ◽  
Post Hoc Analysis ◽  
Post Hoc ◽  
Disease Location

Abstract Background CALM was a randomized phase 3 trial in patients with Crohn’s disease (CD) that demonstrated improved endoscopic outcomes when treatment was escalated based on cutoffs for inflammatory biomarkers, fecal calprotectin (FC), C-reactive protein (CRP), and CD Activity Index (CDAI) remission vs CDAI response alone. The purpose of this post hoc analysis of CALM was to identify drivers of treatment escalation and evaluate the association between biomarker cutoff concentrations and endoscopic end points. Methods The proportion of patients achieving CD Endoscopic Index of Severity (CDEIS) &lt;4 and no deep ulcers 48 weeks after randomization was evaluated according to CRP &lt;5 mg/L or ≥5 mg/L and FC &lt;250 μg/g or ≥250 μg/g. Subgroup analyses were performed according to disease location, and sensitivity analyses were conducted in patients with elevated CRP and/or FC at baseline. The association between endoscopic end points and biomarker cutoffs was performed using χ 2 test. Results The proportion of patients who achieved the primary end point CDEIS &lt;4 and no deep ulcers was significantly greater for those with FC &lt;250 µg/g (74%; P &lt; 0.001), with an additive effect for CRP &lt;5 mg/L. The association of FC &lt;250 µg/g with improved endoscopic outcomes was independent of disease location, although the greatest association was observed for ileocolonic disease. Fecal calprotectin &lt;250 µg/g, CRP &lt;5 mg/L, and CDAI &lt;150 gave a sensitivity/specificity of 72%/63% and positive/negative predictive values of 86%/42% for CDEIS &lt;4 and no deep ulcers 48 weeks after randomization. Conclusion This post hoc analysis of CALM demonstrated that a cutoff of FC &lt;250 µg/g is a useful surrogate marker for mucosal healing in CD.

scholarly journals P141 IBUS-SAS for Crohn’s disease ultrasound activity: initial validation and research of the optimal cut-off score

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S226-S227
Author(s):  
G Dragoni ◽  
T Innocenti ◽  
E N Lynch ◽  
C Fiorini ◽  
L Parisio ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Inflammation ◽  
Real Life ◽  
Area Under The Curve ◽  
Mean Value ◽  
Clinical Activity ◽  
Faecal Calprotectin ◽  
Reactive Protein ◽  
International Panel

Abstract Background Intestinal ultrasound (IUS) is being widely accepted as a reliable tool to objectively monitor Crohn’s disease (CD) activity. Recently, an international panel of experts developed an IUS score, called IBUS-SAS (International Bowel Ultrasound Segmental Activity Score). Our aim was to validate this index in a real-life cohort and find a cut-off score that correlates with common lab results of intestinal inflammation. Methods All CD patients referred to our unit for IUS examination between November 2020 and February 2021 were scored with the IBUS-SAS. Clinical activity at the time of presentation using Harvey-Bradshaw Index (HBI) was recorded, with remission defined as HBI&lt;5. Faecal calprotectin (FC) and C-reactive protein (CRP) within 8 weeks from IUS were also included. Upper limits of normal for CRP and FC were set at 0.5 mg/dL and 150 µg/g, respectively. Combined biomarkers remission (CBR) was defined as both negative CRP and FC. Pearson’s correlation (rho = ρ) was performed between IBUS-SAS and the other parameters. ROC analyses were carried out to find a predictive cut-off value of IBUS-SAS for CBR. Results In total, 40 CD patients were included. The characteristics of the cohort are reported in Table 1. In patients in clinical remission, IBUS-SAS was 27.52±17.42 (mean ±SD); in patients with clinical activity, it was 59.23±22.36. In individuals with negative FC, IBUS-SAS mean value was 26.59±16.85; in case of FC &gt;150 µg/g, it was 50.13±22.16. IBUS-SAS score directly correlated with all parameters considered: clinical activity (ρ=0.38, P=0.01), CRP (ρ=0.33, P=0.04) and FC (ρ=0.42, P=0.007). ROC analysis of IBUS-SAS for CBR revealed an area under the curve of 0.92 (95% CI 0.86–0.97), with a sensitivity of 83.3% and a specificity of 91.3% for a cut-off value of 42.9. Conclusion This pilot analysis of IBUS-SAS confirmed its potential to precisely define CD activity, correlating both with clinical scores and biomarkers. An IBUS-SAS cut-off value of 42.9 has demonstrated the highest sensitivity and specificity in predicting normal values of both CRP and FC. A comparison of IBUS-SAS with endoscopic activity and a larger cohort are needed to confirm these findings.

scholarly journals DOP12 Validation of a modified simple ultrasound activity Score for children with Crohn’s Disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S050-S051
Author(s):  
H Ma ◽  
D M Isaac ◽  
A Petrova ◽  
P Almeida ◽  
D Parsons ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activity Index ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Fecal Calprotectin ◽  
Activity Score ◽  
Chi Square ◽  
Minimal Invasiveness ◽  
Reactive Protein

Abstract Background Transabdominal bowel ultrasound (TABUS) is an ideal tool to assess the bowel wall thickness (BWT) of children with Crohn’s disease (CD) due to its minimal invasiveness. Recently the Simple Ultrasound Activity Score for CD (SUS-CD) was developed and validated in adults using the Simple Endoscopic Score for CD (SES-CD). Our aim was to determine how the SUS-CD performed in children at diagnosis in comparison to endoscopy. Methods Pediatric patients (0–18 years old) with suspected inflammatory bowel disease (IBD) were prospectively enrolled through the Edmonton Pediatric IBD Clinic in Alberta, Canada. Patients underwent a baseline TABUS to visualize the intestine (excluding rectum, which is difficult to see with TABUS), blood work and endoscopy. The weighted pediatric CD activity index (wPCDAI) assessed disease activity, and SES-CD assessed endoscopic disease. Modified SUS-CD (excluding rectal sub score) was calculated using BWT scores (0=&lt;3mm, 1=3–4.9mm, 2=5–7.9mm, 3=&gt;8mm) and colour doppler scores (0=no or 1 vessel, 1=2–5 vessels, 2=&gt;5 vessels per cm2) for each segment (terminal ileum, right colon, transverse colon, left colon) and compared to SES-CD. Modified SUS-CD was correlated to wPCDAI score, C-reactive protein (CRP) and fecal calprotectin (FCP). Using SPSS, anova and Chi square were used to assess for an association between TABUS parameters and wPCDAI. Spearman’s rank (rho) and Pearson’s correlation (r) were used to assess for a correlation between modified SUS-CD with SES-CD, wPCDAI, CRP and FCP. Results 40 patients recruited, 35 had CD (mean age 12.6(2.85)) and 5 were normal and scanned for suspected IBD (mean age 12.2(3.75)). Median wPCDAI and SES-CD scores for CD patients were 61(IQR 35.6–77.5) and 15(IQR 7.5–21) respectively. Fat proliferation was associated with severe CD based on wPCDAI (p&lt;0.05). The modified SUS-CD score correlated well with the modified SES-CD score (rho=0.79,r=0.76,p&lt;0.001,R2 linear=0.465). When the BWT threshold was lowered by 0.5mm for each BWT category, correlation improved (rho=0.80,r=0.82,p&lt;0.001,R2 Linear=0.541). Using a similar lower threshold for BWT, a receiver operating characteristic curve analysis revealed an area under the curve of 0.87 and 0.90 for detecting mild endoscopic activity and moderate endoscopic activity, respectively. There was a significant correlation between SUS-CD and wPCDAI score (r=0.56,p&lt;0.01), CRP (r=0.55,p&lt;0.01) and FCP (r=0.56,p&lt;0.01). Conclusion Fat proliferation was associated with more severe CD. The modified SUS-CD correlated well with modified SES-CD score, wPCDAI, CRP and FCP. Correlation improved when BWT threshold in each category was dropped by 0.5mm. These data support the use of TABUS as an effective adjunct to the assessment of pediatric CD.

scholarly journals Sustained Crohn’s Disease Remission with an Exclusive Elemental and Exclusion Diet: A Case Report

2021 ◽  
Vol 3 (3) ◽  
pp. 129-138
Author(s):  
Farhad Mehrtash
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Fecal Calprotectin ◽  
Published Data ◽  
Reactive Protein ◽  
Markers Of Inflammation ◽  
Increased Risk ◽  
Bowel Diseases ◽  
Exclusion Diet ◽  
Standard Medical Treatment

The incidence of inflammatory bowel diseases, such as Crohn’s disease (CD), is increasing worldwide. Despite several new therapeutics to treat CD, many patients fail to respond to their medications and inevitably face surgical resection. While genetics plays a role in CD, environmental factors are potential triggers. Recent research from the past few years suggest that pro-inflammatory foods are associated with an increased risk of CD. Some studies have shown the benefit of including exclusion diets, such as the specific carbohydrate diet (SCD) and exclusive elemental diets, to induce CD remission, but published data is limited. This case study explores how an exclusive elemental and exclusion diet helped induce clinical and biochemical remission and radiologic healing in a young adult male who had failed to achieve remission using standard medical treatment. C-reactive protein (CRP), fecal calprotectin, and magnetic resonance enterography (MRE) served as objective markers of inflammation in this study.

Outcomes of Passable and Non-passable Strictures in Clinical Trials of Crohn’s Disease: A Post-hoc Analysis

2021 ◽  
Author(s):  
Neeraj Narula ◽  
Emily C L Wong ◽  
Parambir S Dulai ◽  
John K Marshall ◽  
Jean-Frederic Colombel ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activity Index ◽  
Disease Activity Index ◽  
Symptom Improvement ◽  
Logistic Regression Models ◽  
Post Hoc Analysis ◽  
Endoscopic Remission ◽  
Post Hoc ◽  
The Impact

Abstract Background and Aims There is paucity of evidence on the reversibility of Crohn’s disease [CD]-related strictures treated with therapies. We aimed to describe the clinical and endoscopic outcomes of CD patients with non-passable strictures. Methods This was a post-hoc analysis of three large CD clinical trial programmes examining outcomes with infliximab, ustekinumab, and azathioprine, which included data on 576 patients including 105 with non-passable strictures and 45 with passable strictures, as measured using the Simple Endoscopic Score for Crohn’s Disease [SES-CD]. The impact of non-passable strictures on achieving clinical remission [CR] and endoscopic remission [ER] was assessed using multivariate logistic regression models. CR was defined as a Crohn’s Disease Activity Index [CDAI] &lt;150, clinical response as a CDAI reduction of ≥100 points, and ER as SES-CD score &lt;3. Results After 1 year of treatment, patients with non-passable strictures demonstrated the ability to achieve passable or no strictures in 62.5% of cases, with 52.4% and 37.5% attaining CR and ER, respectively. However, patients with non-passable strictures at baseline were less likely to demonstrate symptom improvement compared with those with passable or no strictures, with reduced odds of 1-year CR (adjusted odds ratio [aOR] 0.17, 95% CI 0.03–0.99, p = 0.048). No significant differences were observed between patients with non-passable strictures at baseline and those with passable or no strictures in rates of ER [aOR 0.82, 95% CI 0.23–2.85, p = 0.751] at 1 year. Conclusions Patients with non-passable strictures can achieve symptomatic and endoscopic remission when receiving therapies used to treat CD, although they are less likely to obtain CR compared with patients without non-passable strictures. These findings support the importance of balancing the presence of non-passable strictures in trial arms.

Combined evaluation of fecal calprotectin and C-reactive protein as a therapeutic target in the management of patients with Crohn's disease

2021 ◽  
Vol 44 (2) ◽  
pp. 87-95
Author(s):  
Francisco Guilherme Cancela Penna ◽  
Rodrigo Macedo Rosa ◽  
Fernando H. Pereira ◽  
Pedro Ferrari Sales Cunha ◽  
Stella Cristina S. Sousa ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Therapeutic Target ◽  
Fecal Calprotectin ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Combined Evaluation

scholarly journals DOP019 Effect of vedolizumab treatment on extraintestinal manifestations in patients with Crohn’s disease: a GEMINI 2 post hoc analysis

2017 ◽  
Vol 11 (suppl_1) ◽  
pp. S36-S38
Author(s):  
B.G. Feagan ◽  
W.J. Sandborn ◽  
J.-F. Colombel ◽  
S. O’Byrne ◽  
J.M. Khalid ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Extraintestinal Manifestations ◽  
Post Hoc Analysis ◽  
Post Hoc

scholarly journals The New Proactive Approach and Precision Medicine in Crohn’s Disease

Biomedicines ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 193
Author(s):  
Eran Zittan ◽  
Ian M. Gralnek ◽  
Marc S. Berns
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Personalized Medicine ◽  
Precision Medicine ◽  
Unmet Need ◽  
Fecal Calprotectin ◽  
Mucosal Inflammation ◽  
Remission Induction ◽  
Clinical Relapse ◽  
Proactive Approach

The proactive approach to Crohn’s disease (CD) management advocates moving toward algorithmic tight-control scenarios that are designed for each CD phenotype to guide remission induction, maintenance therapy, active monitoring, and multidisciplinary care to manage the complexities of each inflammatory bowel disease (IBD) patient. This requires accurate initial clinical, laboratory, radiological, endoscopic, and/or tissue diagnosis for proper phenotypic stratification of each CD patient. A substantial proportion of patients in symptomatic remission have been reported to demonstrate evidence of active disease, with elevated fecal calprotectin(FC) and C-reactive protein (CRP) levels as a hallmark for mucosal inflammation. Active mucosal inflammation, and elevated CRP and fecal calprotectin (FC) have been shown to be good predictors of clinical relapse, disease progression, and complications in IBD patients. The next frontier of treatment is personalized medicine or precision medicine to help solve the problem of IBD heterogeneity and variable responses to treatment. Personalized medicine has the potential to increase the efficacy and/or reduce potential adverse effects of treatment for each CD phenotype. However, there is currently an unmet need for better elucidation of the inflammatory biopathways and genetic signatures of each IBD phenotype, so personalized medicine can specifically target the underlying cause of the disease and provide maximal efficacy to each patient.

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