At the early stage of mucosal inflammation in patients with inflammatory Bowel Diseases
(IBD), neutrophils flood into intestinal mucosa, phagocytose pathogenic microbes, and
promote mucosal healing and resolution of inflammation. However, large numbers of
neutrophils infiltrating in the inflamed mucosa and accumulating in the epithelium cause
damage of mucosal architecture, compromised epithelial barrier and production of
inflammatory mediators. Novel neutrophil-related serum markers are emerging in the
literature and are valid candidates to surrogate markers for mucosal healing (MH). NGAL
is an anti-bacterial protein, whereas MMP-9 is a protein with enzymatic activity towards
extracellular matrix (ECM) and non-ECM components, and is involved in cell signaling.
By formation of a complex between NGAL and MMP-9, NGAL is thought to protect MMP-9 from
autodegradation. Cathelicidin LL37 is the 37 amino acids C-terminal part of human
cationic antimicrobial protein (hCAP)18 and acts as an antimicrobial protein (AMP). It is
found in lysosomes of macrophages and polymorphonuclear leukocytes (PMNs) as well as
keratinocytes and plays a role in the early host response against invading pathogens via
its broad-spectrum anti-microbial activity. The expression of LL37 was found to be
increased in the inflamed mucosa of patients with UC and CD3. Moreover, increased colonic
LL37 expression in macrophages and epithelium was observed during colitis in UC patients.
Chitinase 3 like 1 (CHI3L1), also known as YKL-40, is a 39 kDa secreted glycoprotein
member of the glycosyl hydrolase 18 family although it does not show chitotriosidase
activity. It is secreted by macrophages and neutrophils and acts as a growth factor for
vascular endothelial cells and fibroblasts.
In previous retrospective single-site study, consisting of serum samples and endoscopic
evaluation before and after anti-TNFa treatment from 176 moderate-to-severe UC patients
and 75 healthy controls, showed that the combined use of these markers is statistically
significant and can accurately correlate with the Mayo endoscopic subscore (MES) and
identify endoscopic response to infliximab (IFX) and adalimumab (ADM. An algorithm, the
Ulcerative Colitis Response Index (UCRI), a unit-less index ranging from 0 (likely a
responder) to 10 (likely a non-responder) was constructed and identified accentually the
anti-TNFa non-responders' patients as measured by endoscopic assessment MES ≥2.
Glycominds, LLC (the "Sponsor") in support of the Crohn's and Colitis Foundation (CCF)
IBD Venture will conduct this prospective multicenter longitudinal study in the U.S.
Following screening and patient enrollment based on the inclusion and exclusion criteria
Imaging, blood (serum) and fecal samples will be collected at certain predefined time
points from bio naïve (naïve) and from anti-TNFa previously exposed (exposed) active (MES
>2) UC patients that will start an anti-TNFa treatment or switch from one anti-TNFa type
to another (infliximab-IFX or biosimilars, adalimumab-ADM, golimumab-GOM) at time of
recruitment. Collected blood and stool samples will be used to determine the accuracy and
prediction value of the UCRI biomarker panel and algorithm in comparison with endoscopic
healing (measured as end point of MES ≤ 2) and in comparison to fecal Calprotectin. The
IFX/ADM/GOM treatment decision and endoscopic evaluations before and after treatment
initiation/switching will be done according to current clinical practice and Sponsor will
not have any influence or responsibilities on those decisions.
