Neutrophil-Related Serum Markers Accurately Detect Mucosal Healing in Ulcerative Colitis

Ulcerative colitis
ulcerative colitis, inflammatory bowel disease, IBD, UC
Prospective studies are needed to validate the Ulcerative Colitis Response Index algorithm as a surrogate marker panel for mucosal healing, with the ultimate goal being to avoid unnecessary endoscopic evaluations.

A recent publication in the Journal of Crohn’s and Colitis reports the development of a novel Ulcerative Colitis Response Index (UCRI) that accurately detects mucosal healing after treatment with anti-tumor necrosis factor (anti-TNF).

Although other biomarkers have previously been developed, they are not sensitive or specific enough for patients with UC to avoid endoscopic evaluations to assess mucosal healing. Therefore, de Bruyn and colleagues developed the UCRI as a surrogate marker, aiming to avoid the need for endoscopic evaluation.

To make the index, the investigators combined novel serum neutrophil-related markers, neutrophil gelatinase B-associated lipocalin and matrix metalloproteinase-9 (NGAL-MMP-9 complex), the human antimicrobial protein cathelicidin LL-37 (LL-37), and chitinase 3-like 1 (CHI3L1), which acts as a growth factor for vascular endothelial cells and fibroblasts, with C-reactive protein (CRP), and neutrophil count.

To calculate the UCRI’s discriminative power to detect mucosal healing in patients with UC after anti-TNF treatment, the study authors obtained serum samples from 176 treated patients with UC (infliximab, 145; adalimumab, 31) at baseline and after initiating treatment (median, 9.5 weeks). Samples from healthy control participants were also included in the study (n=75). Markers and the UCRI were tested with receiver operating characteristic analysis (area under the curve [AUC]).

Before treatment, all patients had active disease according to the Mayo endoscopic subscore (≥2), and mucosal healing was defined as a subscore of ≤1. At baseline, all neutrophil-related markers (NGAL-MMP-9 complex, LL37, and CHI3L1) were significantly higher in patients with UC compared with the healthy control individuals.

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After initiating treatment, the infliximab cohort had significantly decreased levels of CRP, NGAL-MMP-9, CHI3L1, and neutrophil count, and when comparing patients with or without mucosal healing, all marker levels were significantly lower in healers than in nonhealers.

Although most differences in serum marker levels before and after treatment in the adalimumab cohort were not significant, CRP, NGAL-MMP-9, CHI3L1, and neutrophil count decreased significantly in patients with healing relative to those without healing.

Most individual markers (CRP, CHI3L1, neutrophil count, and LL-37) accurately detected mucosal healing in both treatment groups, and combining the markers increased discriminative performance; therefore, those 4 makers were included in the final UCRI (infliximab-treated, AUC = 0.83; and adalimumab-treated, AUC = 0.79).

Limitations of the study included its retrospective design, unavailable information on fecal calprotectin levels, and a small sample size for the adalimumab cohort. However, the authors highlighted that the exploratory cohort increases the value of this a proof-of-concept study.

“We therefore propose a broad clinical utility of this biomarker panel for monitoring mucosal healing in UC patients under anti-TNF treatment. Further independent, prospective studies are needed to increase patient numbers and validate the UCRI algorithm as a surrogate marker panel for mucosal healing with the ultimate goal to avoid unnecessary endoscopic evaluations in our patients,” concluded the authors.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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de Bruyn M, Ringold R, Martens E, et al. The ulcerative colitis response index for detection of mucosal healing in patients treated with anti-tumour necrosis factor. J Crohns Colitis. 2020;14(2):176-184.