P357 Serological biomarkers of interstitial matrix and basement membrane remodelling correlate to disease activity in Crohn’s disease

Abstract Background In Crohn’s disease (CD) Smad7 is overexpressed in the intestinal mucosa, where it contributes to a sustained production of inflammatory cytokines, increased matrix metalloproteinase (MMP) activity and chronic inflammation through inhibition of the anti-inflammatory actions of TGF-beta. GED-0301, an anti-sense oligodeoxynucleaotide complementary to the mRNA of Smad7, inhibits the translation and synthesis of the Smad7 protein. We investigated exploratory biomarkers of collagen degradation by MMPs (C1M, C3M, C4M) and collagen formation (PRO-C3, PRO-C4 and PRO-C5) and their association with endoscopic remission in CD patients treated with GED-0301. Methods 63 CD patients were randomized (1:1:1) to 4, 8 or 12 weeks oral, blinded GED-0301 160 mg daily (ClinicalTrials.gov no: NCT02367183). Simple endoscopic score for CD (SES-CD) (centrally read) was used to evaluate disease activity. Remission was defined as a SES-CD≤4 score at week 12. 54 CD patients completed the 12-week induction phase. Serum biomarkers measured by competitive ELISA se included C1M, C3M, C4M, PRO-C3, PRO-C4, PRO-C5 at baseline, week 4, week 8 and week 12. Spearman rho correlation was applied to evaluate the association with biomarkers and SES-CD score. Results Seven patients (11%) achieved a SES-CD≤4 at week 12. At baseline and at week 12 the biomarkers, C1M (baseline: r=0.36, P=0.005; wk12: r=0.47, P=0.0007), C3M (baseline: r=0.46, P=0.0002; wk12: r=0.28, P=0.047), C4M (baseline: r=0.40, P=0.002; wk12: r=0.36, P=0.011) PRO-C4 (baseline: r=0.36, P=0.004; wk12: r=0.35, P=0.013), and PRO-C5 (baseline: r=0.30, P=0.022) correlated with SES-CD (table 1). Remitters at baseline showed a numerically lower serum levels of C1M (54ng/mL vs. 65ng/mL), C3M (14.7ng/mL vs. 16.5ng/mL), PRO-C4 (241ng/mL vs. 299ng/mL) and PRO-C5 (442ng/mL vs. 660ng/mL) compared to non-remitters. The biomarkers C1M (P<0.05), C4M (P<0.05) and PRO-C5 (P<0.05) were significantly suppressed in remitters at week 12 compared to non-remitters (figure 1). The same biomarkers also demonstrated sustained suppression of serum concentrations at week 4, 8 and 12 (C1M: 21.6% decrease from baseline at week 12; C4M: 15% decrease from baseline at week 12; PRO-C5: 26.6% decrease from baseline at week 12) in remitters compared to non-remitters. Conclusion Biomarkers of tissue remodeling correlated with the SES-CD scores of CD patients treated with mongersen. Patients s who achieved remission based on endoscopic criteria showing greater suppression of these biomarkers relative to non-remitters. Collectively, these data suggest that biomarkers of tissue remodeling may be useful to monitoring disease activity and mucosal changes in CD patients.

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Induction of β-defensin expression in Crohn's disease: Activity relate expression profile and subtype selective upregulation in gastrointestinal tissues

Gastroenterology ◽

10.1016/s0016-5085(01)81588-2 ◽

2001 ◽

Vol 120 (5) ◽

pp. A320-A320

Author(s):

A DEWEERTH ◽

M BLAEKER ◽

A REISSER ◽

M SCHULZ

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Expression Profile ◽

Crohn’S Disease Activity ◽

Subtype Selective

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P112 STUDY OF THE PROTEOMIC PROFILE IN PATIENTS WITH CROHN’S DISEASE, ITS CORRELATION WITH DIAGNOSIS AND DISEASE ACTIVITY

Gastroenterology ◽

10.1053/j.gastro.2017.11.158 ◽

2018 ◽

Vol 154 (1) ◽

pp. S58

Author(s):

Salah Badr El-Din ◽

Ezzat Ahmed ◽

Doaa Header ◽

Pacint Moez ◽

Mohamed Ibrahim

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Proteomic Profile

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

Nuklearmedizin ◽

10.1055/s-0038-1629438 ◽

1988 ◽

Vol 27 (03) ◽

pp. 83-86 ◽

Cited By ~ 3

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.

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Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in inflammatory bowel disease receiving adalimumab: PLANET study

Journal of Gastroenterology ◽

10.1007/s00535-021-01793-0 ◽

2021 ◽

Author(s):

Shinichiro Shinzaki ◽

Katsuyoshi Matsuoka ◽

Hiroki Tanaka ◽

Fuminao Takeshima ◽

Shingo Kato ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Bowel Disease ◽

Fecal Calprotectin ◽

Potential Biomarker ◽

Adalimumab Therapy ◽

Adalimumab Treatment ◽

Inflammatory Bowel

Abstract Background This multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease activity in inflammatory bowel disease (IBD). Methods Patients with moderate-to-severe IBD initiated on adalimumab therapy were enrolled herein. Serum LRG, C-reactive protein (CRP), and fecal calprotectin (fCal) levels were measured at week 0, 12, 24, and 52. Colonoscopy was performed at week 0, 12, and 52 for ulcerative colitis (UC), and at week 0, 24, and 52 for Crohn’s disease (CD). Endoscopic activity was assessed using the Simple Endoscopic Score for Crohn’s Disease (SES-CD) for CD and the Mayo endoscopic subscore (MES) for UC. Results A total of 81 patients was enrolled. Serum LRG levels decreased along with improvements in clinical and endoscopic outcomes upon adalimumab treatment (27.4 ± 12.6 μg/ml at week 0, 15.5 ± 7.7 μg/ml at week 12, 15.7 ± 9.6 μg/ml at week 24, and 14.5 ± 6.8 μg/ml at week 52), being correlated with endoscopic activity at each time point (SES-CD: r = 0.391 at week 0, r = 0.563 at week 24, r = 0.697 at week 52; MES: r = 0.534 at week 0, r = 0.429 at week 12, r = 0.335 at week 52). Endoscopic activity better correlated with LRG compared to CRP and fCal on pooled analysis at all time points (SES-CD: LRG: r = 0.636, CRP: r = 0.402, fCal: r = 0.435; MES: LRG: r = 0.568, CRP: 0.389, fCal: r = 0.426). Conclusions Serum LRG is a useful biomarker of endoscopic activity both in CD and UC during the adalimumab treatment.

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Letter: assessment of histological disease activity in Crohn's disease clinical trials—a step in the right direction, but further optimisation needed

Alimentary Pharmacology & Therapeutics ◽

10.1111/apt.16450 ◽

2021 ◽

Vol 54 (4) ◽

pp. 541-542

Author(s):

Andrew H. Tsoi ◽

Anand Murugasu ◽

Mayur Garg

Keyword(s):

Clinical Trials ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

The Right

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Relevance of monitoring transmural disease activity in patients with Crohn’s disease: current status and future perspectives

Therapeutic Advances in Gastroenterology ◽

10.1177/17562848211006672 ◽

2021 ◽

Vol 14 ◽

pp. 175628482110066

Author(s):

Rune Wilkens ◽

Kerri L. Novak ◽

Christian Maaser ◽

Remo Panaccione ◽

Torsten Kucharzik

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Symptom Control ◽

Current Status ◽

Clinical Relapse ◽

Cross Sectional ◽

Treatment Targets ◽

Endoscopic Remission ◽

Transmural Inflammation

Treatment targets of inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD) have evolved over the last decade. Goals of therapy consisting of symptom control and steroid sparing have shifted to control of disease activity with endoscopic remission being an important endpoint. Unfortunately, this requires ileocolonoscopy, an invasive procedure. Biomarkers [C-reactive protein (CRP) and fecal calprotectin (FCP)] have emerged as surrogates for endoscopic remission and disease activity, but also have limitations. Despite this evolution, we must not lose sight that CD involves transmural inflammation, not fully appreciated with ileocolonoscopy. Therefore, transmural assessment of disease activity by cross-sectional imaging, in particular with magnetic resonance enterography (MRE) and intestinal ultrasonography (IUS), is vital to fully understand disease control. Bowel-wall thickness (BWT) is the cornerstone in assessment of transmural inflammation and BWT normalization, with or without bloodflow normalization, the key element demonstrating resolution of transmural inflammation, namely transmural healing (TH) or transmural remission (TR). In small studies, achievement of TR has been associated with improved long-term clinical outcomes, including reduced hospitalization, surgery, escalation of treatment, and a decrease in clinical relapse over endoscopic remission alone. This review will focus on the existing literature investigating the concept of TR or residual transmural disease and its relation to other existing treatment targets. Current data suggest that TR may be the next logical step in the evolution of treatment targets.

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