Introduction

The development of anti-TNF agents has brought major advances in the treatment of ulcerative colitis (UC), however, many patients still require the use of 2^nd-, 3^rd-, or even 4^th-line biologicals or small molecules.

Aims & Methods

We conducted a retrospective, multicentre study with the inclusion of UC patients who failed anti-TNF therapy due to primary non-response (PNR) or loss of response (LOR), and received sequential biological treatment for moderate-to-severe disease activity or for acute, severe exacerbation (ASUC). The primary aim was to evaluate and compare the effectiveness of 2^nd-, 3^rd-, or 4^th-line biological or small molecule therapies after anti-TNF failure. Treatment effectiveness was determined by persistence and colectomy-free survival. Logistic regression analysis was performed to identify the predictive value of demographic factors, clinical, endoscopic, and laboratory parameters for colectomy.

Results

To date, 454 UC patients have been included. The median follow-up time was 57.7 months (IQR: 92.9-33.3). The indication for the 1^th-line anti-TNF therapy was chronic, refractory UC in 307(67.6%) and ASUC in 147(32.4%) patients. The rate of PNR, as reason for treatment discontinuation progressively increased in accordance with the lines of sequential treatment (23.1%/31.7%/36.2%/45.0%), however, the incidence of LOR did not show a definite tendency among the various therapeutic lines (50.0%/56.1%/58.0%/40.0%). A significant difference with treatment persistence was seen among the most frequently used biologicals and small molecules following anti-TNF failure (Table 1.). Ustekinumab (UST) had superior persistence compared to vedolizumab (VDZ) and tofacitinib (TOFA) at 3, 6, 12 and 24 months, regardless of the number of previous anti-TNFs. The overall colectomy rate was 15.6%, mostly due to chronic, refractory UC (61.9%). The probability of colectomy-free survival was 97.2%, 93.3% and 91.2% at 1, 2 and 3 years, respectively. Cyclosporine use during the course of the disease proved to be protective against colectomy (OR: 2.88, 95% CI: 1.447-5.733, p=0.0026). Pancolitis (OR: 3.24, 95% CI: 1.604-6.562, p=0.0012) appeared to be predictive for colectomy. Following anti-TNF failure, the incidence of colectomy was shown to be significantly lower with 2^nd-line UST (n=3 (5.8%), p=0.0422) than with VDZ (n=57 (16.8%)) or TOFA (n=11 (20.4%)).

Conclusion

According to the preliminary results of this ongoing cohort, sequential therapy was effective in avoiding colectomy in 84.4% of the patients and even after multiple lines of treatment we could expect a relatively low rate of colectomy. UST, as a 2^nd-line therapy after anti-TNF failure, was significantly superior, both in terms of persistence and colectomy-free survival, compared to VDZ or TOFA. Cyclosporine use reduced the risk of colectomy, while pancolitis was seen to be a predictive factor for surgery. Further analysis are being performed to identify factors that influence the efficacy of non-TNF agents and to clarify their role in the subsequent therapeutic lines.

Introduction

There is limited research on HealthCare Resource Utilization (HCRU) and costs among patients receiving ustekinumab (UST) treatment. This study aims to evaluate HCRU and costs in patients with Crohn's Disease (CD) and Ulcerative Colitis (UC) who received UST treatment through Janssen’s BIOADVANCE® patient support program (PSP) in Ontario, Canada.

Aims & Methods

The primary objective of this study is to compare annual HCRU and costs (excluding medication expenses) during a period of one year before initiating UST treatment and up to four years post-initiation.
This retrospective observational study analyzed data from a consecutive cohort of Ontario CD and UC patients who initiated UST treatment through Janssen’s BIOADVANCE® PSP.
Patients were indexed based on their first recorded UST prescription fill, spanning from January 1, 2017, to July 31, 2021, for CD patients, and from February 1, 2020, to July 31, 2021, for UC patients.
Quasi-identifiers (date of birth, gender, postal code, indication) were used for probabilistic linkage of patients in BIOADVANCE® PSP to those in Ontario Crohn’s and Colitis Cohort (OCCC) from the Institute for Clinical Evaluative Sciences (ICES). A follow-up period for up to four years post-index date was used to assess all-cause and IBD-specific HCRU and costs. A 12-month lookback period was utilized to establish baseline demographic and clinical profiles and baseline HCRU and costs. A mixed gamma regression model was employed to compare costs before and after UST initiation. IBD-specific HCRU and costs included general practitioner visits, specialist visits, emergency department visits, inpatient hospitalization, and same-day surgeries. IBD-specific HCRU and costs were identified based on the IBD-specific diagnosis code as the most responsible diagnosis.

Results

A probabilistic linkage of 88.1% for CD cases and UC cases was achieved. A total of 2,279 patients with CD and 626 patients with UC were included. UST was the initial biologic therapy for 35.72% and 22.68% of patients with CD and UC, respectively. The average time since diagnosis was 10.72 years for CD and 8.07 years for UC. The mean age was 45.6 ± 17.2 years for UC patients and 45.7 ± 16.2 years for CD patients. UC showed a male-female ratio of 56% to 44%, whereas for CD, it was 46% to 54%.
IBD-specific HCRU and costs significantly decreased post-UST initiation in Years 1, 2, and 3 for both CD patients and UC patients, compared to baseline.
[See Table]

Conclusion

Initiation of UST through the BIOADVANCE® PSP was related to substantial reductions in IBD-specific HCRU and costs among patients with CD and UC in Ontario, Canada. These findings underscore the potential benefits of UST as an advanced therapy in IBD treatment, in managing CD and UC, and support its role in optimizing patient outcomes while reducing the burden on healthcare resources.

References

Data source:

1. Janssen BIOADVANCE® Database (January 1, 2016 – March 31, 2023) and Ontario Crohn’s and Colitis Cohort (OCCC) data in Institute for Clinical Evaluative Sciences (ICES).

Disclosure

Laura Targownik has received grants from AbbVie Canada, Janssen Canada and Pfizer Canada; consulting fees from AbbVie, Takeda, Janssen, Pfizer, Amgen, Viatris, Fresenius Kabi, Bristol Myers Squibb, Sanofi, Lilly; honoraria from AbbVie, Takeda, Janssen, Pfizer, Amgen, Viatris, Fresenius Kabi, Bristol Myers Squibb, Sanofi; has participated on a data safety monitoring board of advisory board for GoodCap Pharmaceuticals, Pfizer, Takeda, Janssen, Bristol Myers Squibb, and is a member of the Crohn’s and Colitis Canada Scientific and Medical Advisory Board; Eneda Pone, Martin G. Latour, and Kasra Boyerahmadi are Janssen employee, and Huijuan Yang, Juejing Ling, Ali Tehrani, and Shane Golden are employee of IQVIA, and John K Marhsall is a consultant for AbbVie, Amgen, Bausch Health, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, Lilly, Organon, Paladin, Pfizer, Pharmascience, Roche, Sandoz, Takeda, Viatris and a speaker for AbbVie, Amgen, Bausch Health, Ferring, Fresenius Kabi, Janssen, Lupin, Organon, Pfizer, Pharmascience, Roche, Takeda.

Introduction

Mirikizumab [(miri), a p19-directed IL-23 antibody] has been shown to be effective in patients with moderately to severely active ulcerative colitis (UC) in Phase 3, randomised, double-blind, placebo-controlled trials (LUCENT-1 NCT03518086; LUCENT-2 NCT03524092).¹ Given the importance of understanding treat-to-target strategies, the relationship between improved histologic and endoscopic endpoints and improvement of the inflammatory biomarkers faecal calprotectin (fCal) and C-reactive protein (CRP) was studied within miri-treated patients enrolled in the programme.

Aims & Methods

This analysis focused on miri-treated patients (n=868) from the induction study receiving intravenous (IV) every 4 weeks (Q4W) until week (W)12 and miri induction responders at week W12, who were rerandomised for the maintenance period, receiving subcutaneous miri (n=365) Q4W up to W52. The relationship between achieving histologic-endoscopic mucosal improvement (HEMI), histologic-endoscopic mucosal remission (HEMR) (definitions in Tables) and improvement of fCal (≤250µg/g) and CRP (≤6mg/L) levels at W12 and W52 was explored using Fisher’s exact tests.

Results

At W12, a significantly higher percentage of miri-treated patients achieving HEMI (n=235/868) had normalised fCal and CRP values (76.2% and 88.5%), compared to miri-treated patients who did not achieve HEMI (n=633/868) (21.8% and 72.7%, both p<0.001; Table). Similarly, a higher proportion of patients achieving HEMR (n=193/868) had normalised fCal and CRP values (79.3% and 89.6%), compared to those who did not achieve HEMR (n=675/868) (24.3% and 73.3%, both p<0.001; Table). At W52, a significantly higher percentage of the miri induction responder patients rerandomised to miri achieving HEMI (174/365) had normalised fCal and CRP values (74.1% and 87.9%), compared to patients not achieving HEMI (191/365) (32.5% and 61.3%; both p<0.001). Similarly, at W52, a higher proportion of patients achieving HEMR (n=158/365) had normalised fCal and CRP values (76.6% and 88.0%), versus patients not achieving HEMR (n=207/365) (33.8% and 63.3%; both p<0.001, Table).

Conclusion

At both W12 and W52, patients treated with miri who achieved HEMI or HEMR showed statistically significant improvements in fCal and CRP levels. This suggests that CRP and fCal may be useful markers of histology and endoscopy outcomes after induction and maintenance with miri.

References

1. Magro et al., MP245 Efficacy of mirikizumab in resolving active histologic inflammation in Ulcerative Colitis in Lucent-1 induction and Lucent-2 maintenance trials (2022), UEG Week Moderated Posters. United European Gastroenterol J, 10: 185-472.

Disclosure

R. Panaccione has received speaker fees and/or served as a consultant and/or advisory board member for: Abbott, AbbVie, Alimentiv, Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Cosmo Pharmaceuticals, Eisai, Elan Pharma, Eli Lilly and Company, Ferring Pharmaceuticals, Galapagos NV, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Mylan, Oppilan Pharma, Pandion Therapeutics, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda, Theravance Biopharma and UCB Pharma; and has received research and/or educational support from: AbbVie, Ferring Pharmaceuticals, Janssen, Pfizer and Takeda; C. Sapin, F. Chan-Diehl and R. Moses are employees and shareholders of: Eli Lilly and Company;
B. Siegmund has served as a consultant and/or speaker for: AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb, Boehringer Ingelheim, CED Service GmbH, Celgene, Dr Falk Pharma, Eli Lilly and Company, Ferring Pharmaceuticals, Galapagos NV, Janssen, Novartis, Pfizer, Prometheus Therapeutics and Takeda;
A. Walsh has received grant and/or research support from: AbbVie and Pfizer; and has received consultancy fees from: AbbVie, Eli Lilly and Company, Novartis and UCB Pharma;
T. Kobayashi has served as a speaker, consultant and advisory board member for: AbbVie, Ajinomoto Bio-Pharma, Alfresa Pharma, Asahi Kasei Pharma, Astellas, Bristol Myers Squibb, Celltrion, Covidien, EA Pharma, Eisai, Eli Lilly and Company, Ferring Pharmaceuticals, Galapagos NV, Gilead Sciences, Janssen, JIMRO, Kyorin, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda, Thermo Fisher Scientific and Zeria Pharmaceutical; and has received research funding from: AbbVie, ActivAid, Alfresa Pharma, Asahi Kasei Pharma, EA Pharma, Google, JMDC, Kyorin, Mochida Pharmaceutical, Nippon Kayaku, Otsuka, Sekisui Medical, Thermo Fisher Scientific and Zeria Pharmaceutical;
P. S. Dulai has served as a consultant for: AbbVie, Abivax, Addiso, Bristol Myers Squibb, Eli Lilly and Company, Janssen, Pfizer, Precidiag, Prometheus and Takeda;
S. Travis has received grants from: AbbVie, BUHLMANN Diagnostics, ECCO, Eli Lilly and Company, Ferring Pharmaceuticals, International Organization for the Study of Inflammatory Bowel Disease, Janssen, Merck Sharp & Dohme, Norman Collision Foundation, Pfizer, Procter & Gamble, Schering-Plough, Takeda, UCB Pharma, Vifor Pharma and Warner Chilcott; and reports other disclosures from: Abacus Pharma, AbbVie, Actial Farmaceutica, ai4gi, Alcimed, Allergan, Amgen, Aptel, Arena Pharmaceuticals, Asahi Kasei Pharma, Aspen Pharmacare, Astellas, AstraZeneca, Atlantic Pharmaceuticals, Barco, Biocare Medical, Biogen, BL Pharma, Boehringer Ingelheim, Bristol Myers Squibb, BUHLMANN Diagnostics, Calcico Therapeutics, Celgene, Cellerix, Cerimon Pharmaceuticals, ChemoCentryx, Chiesi, Cisbio, Comcast, Coronado Biosciences, Cosmo Pharmaceuticals, Dr Falk Pharma, Ducentis BioTherapeutics, Dynavax Technologies, Elan, Eli Lilly and Company, Enterome, Equillium, Ferring Pharmaceuticals, Galapagos NV, Genentech/Roche, Genzyme, Gilead Sciences, GlaxoSmithKline, Glenmark Pharmaceuticals, Grünenthal, GW Pharmaceuticals, Immunocore, Indigo Biosciences, Janssen, Lexicon Pharmaceuticals, Medarex, MedTrix, Merck, Merrimack Pharmaceuticals, Mestag Therapeutics, Millennium Pharmaceuticals, Neovacs, Novartis, Novo Nordisk, NPS Pharmaceuticals/Nycomed, Ocera Therapeutics, OPTIMA Pharma, Origin Pharma, Otsuka, Procter & Gamble, Palau Pharma, Pentax Medical, Pfizer, PharmaVentures, Phesi, Phillips Pharma Group, Pronota, Proximagen, Resolute, Robarts Clinical Trials, Sandoz, Santarus, Satisfai Health, Sensyne Health, Shire, Sigmoid Pharma, Sorriso Pharmaceuticals, Souffinez, SynDermix, Synthon, Takeda, Theravance Biopharma, TiGenix, Tillotts Pharma AG, Topivert, Trino Therapeutics with Wellcome Trust, TxCell, UCB Pharma, Vertex Pharma, VHsquared, Vifor Pharma, Warner Chilcott and Zeria Pharmaceutical

Introduction

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are non-infectious chronic inflammatory disorders of the gastro-intestinal tract. The continuous presence of inflammatory stimuli, such as increased circulation of cytokines and danger-associated molecular patterns (DAMPs), leads to an enhanced immune response in these patients that could explain some types of disease relapse. An important receptor for DAMPS and pathogen-associated molecular patterns (PAMPs) is NLRP3, a cytosolic pattern recognition receptor. The NLRP3 inflammasome is exclusively activated by inflammatory stimuli, like DAMPs and PAMPs, and therefore not expressed without inflammation. It is thought that NLRP3 associates with ASC to recruit pro-Caspase 1 to the NLRP3 inflammasome and cleave it to its active form. In turn, Caspase 1 cleaves pro-interleukin 1 beta (IL-1β) and pro-interleukin 18 (IL-18) to their mature forms. IL-1β is a known elevated pro-inflammatory cytokine in IBD, promoting intestinal inflammation and immune cell recruitment. We hypothesized that the NLRP3 inflammasome pathway is therefore upregulated in IBD patients.

Aims & Methods

We first set out to systematically analyze gene expression of NLRP3 and IL1B in IBD patients by performing a systematic literature review and subsequent meta-analysis according to the PRISMA guidelines and Cochrane Collaboration methods. Subsequently, an observational cohort of 70 active and quiescent patients with CD or UC was sampled for whole blood, to study NLRP3 inflammasome gene regulation, protein production, assembly and secretion. We performed ex vivo LPS and ATP challenges of whole blood, with and without NLRP3 inflammasome formation inhibitor MCC950.

Results

Across thirty studies with publicly available mRNA expression data, we found NLRP3 and IL1B expression to be significantly higher in IBD patients than in non-IBD controls. In fresh IBD patient-derived whole blood, LPS and ATP stimulation activated the NLRP3-related genes, protein production and subsequent cytokine secretion. No IL-1β and IL-18 were secreted upon incubation with MCC950, suggesting a crucial role for NLRP3 inflammasome assembly in IL-1β and IL-18 production in immune cells. In patients with active IBD, the inflammasome was transcribed at a higher level than in patients in remission. However, this effect was lost on the protein level. We found a large spread in IL-1β and IL-18 production, suggesting a variation in activation of the NLRP3 inflammasome between individuals which was not related to disease activity.

Conclusion

NLRP3 and IL1B mRNA transcription is significantly increased in IBD patients compared to non-IBD controls, and significantly higher in patients with active disease than in patients in remission. While this fits the inflammatory state of active IBD, we found that the level of IL-1β and IL-18 production by the NLRP3 inflammasome is not significantly different between disease states. This suggests a variance in individual immune response to challenges, that could help identify a subset of IBD patients that would benefit from additional therapies directed at NLRP3 and IL-1β.

Introduction

Inflammatory bowel diseases are chronic disabling conditions with a complex and multifactorial aetiology, which is still not completely understood. OCTN1, an organic cation transporter could have a role in modulating the inflammatory response, whose genetic polymorphisms were associated to increased risk of inflammatory bowel diseases. Up to now, limited information exists on its role in predicting/modulating response to therapies.

Aims & Methods

The aim of this study was to evaluate the role of OCTN1 in modifying gut microbiota and immune composition to Infliximab therapy in murine colitis. Dextran sodium sulphate model of colitis on C57BL/6 mice and ocnt1 gene knockout mice was used to assess clinical efficacy of infliximab administered intravenously. Stool, colon and mesenteric lymph node samples were collected to assess differences in gut microbiota composition, histology for Rachmilewitz score and T cell populations respectively.

Results

Octn1^-/-influences microbiota profile and is associated with a worse dysbiosis in colitis mice. Infliximab treatment attenuates colitis-associated dysbiosis with increase of bacterial richness and evenness in both strains. In comparison with wild type, octn1^-/- mice have a higher baseline percentage of Treg, Tmemory, Th2 and Th17.

Conclusion

Our data support murine model to study OCTN1 genetic asset in inflammatory bowel diseases. This could be the first step to consider this membrane transporter as a biomarker in inflammatory conditions and as a predictor of response to therapies.

Introduction

A key feature of IBD pathogenesis is response dysregulation of both the innate and adaptive immune system^1,2. Hence specific inflammatory protein profiles may be a promising biomarker approach for diagnosis and personalized therapy in IBD. Serum proteome of IBD, particularly in multi-ethnic Asian patients, remains less defined.

Aims & Methods

We aim to investigate the systemic inflammatory protein profiles in multi-ethnic Asian patients with IBD and compare them to healthy controls.
The study cohort was made up of 92 patients with IBD (50.0% Ulcerative colitis (UC), 43.5% Crohn's disease (CD), 6.5% Unclassified IBD)), and 42 control subjects, who are asymptomatic patients undergoing screening colonoscopy with no endoscopic pathology. Serum protein profiling was performed using the Olink Target 96 Inflammation assay. A partial-least square discriminant analysis was undertaken to identify additional discriminative inflammatory proteins. Univariate t-test analyses, with false discovery rate correction, were also performed to identify proteins unique to either UC or CD.

Results

Participants with IBD were younger (42.0 (±14.7) in UC, 43.2 (±15.1) in CD, p<0.01), with greater representation of South Asian ethnicity (32.5% amongst UC, 19.6% amongst CD, p<0.01) and males (75.0% amongst UC, 69.6% amongst CD, p=0.03), as compared to controls.
We found 18 proteins were differentially abundant amongst IBD patients (p<0.05). Half (n=9) of these inflammatory proteins (AXIN-1, CD8A, CXCL1, EN-RAGE, FGF-23, HGF, IL17A, OSM, TGF-alpha) were elevated in both UC and CD. The other six proteins were elevated only in patients with UC (4E-BP1, CCL11, IL-18R1, IL-20, MMP-10, TRANCE). Of the remaining three, two were less abundant in patients with CD (DNER, SCF) and TNF was elevated only in patients with CD. Of interest, three immunoproteins were differentially abundant in participants with either UC or CD (i.e. CCL11, MMP10, TRANCE).

Table1: List of immunoproteins differentially abundant (p<0.05) in varying IBD subtypes, grouped by their key common molecular functions. *indicates that the immunoprotein of interest to be less abundant compared to controls. ^AXIN1 functions - Activation of protein kinase (GO:0032147), WNT signaling process (GO:0016055). ^#MMP-10 function - extracellular matrix organization (GO:0030198). ^$4E-BP1 function - TOR signaling (GO:0031929). ^@DNER function - Notch receptor processing (GO:0007220).

Conclusion

Our pilot study in a multi-ethnic Asian population found distinctive serum protein profile in IBD patients. While some protein changes were shared in both UC and CD, other changes were specific for either UC or CD, suggesting different disease pathways in these two IBD subtypes. We reaffirmed that inflammatory proteins, such as EN-RAGE³, MMP-10⁴ and OSM⁵, were differentially abundant in IBD, consistent with previous reports in predominantly Caucasian cohorts. Further studies with large sample sizes would be required to validate these biomarkers for IBD activity, and prognosis for biologic therapy response.

References

1. Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol. 2014 May;14(5):329-42.
2. Mahida YR. The key role of macrophages in the immunopathogenesis of inflammatory bowel disease. Inflamm Bowel Dis. 2000;6:21–33.
3. Foell D, Kucharzik T, Kraft M, et al. Neutrophil derived human S100A12 (EN-RAGE) is strongly expressed during chronic active inflammatory bowel disease. Gut 2003;52:847-853.
4. Fonseca-Camarillo G, Furuzawa-Carballeda J, Martínez-Benitez B, et al. Increased expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and MMP10, MMP23 in inflammatory bowel disease: Cross-sectional study. Scand J Immunol. 2021 Jan;93(1):e12962.
5. Sare Verstockt, Bram Verstockt, Kathleen Machiels, et al. Oncostatin M Is a Biomarker of Diagnosis, Worse Disease Prognosis, and Therapeutic Nonresponse in Inflammatory Bowel Disease. Inflamm Bowel Dis. 2021 Oct 18;27(10):1564-1575.

Introduction

Inflammatory bowel disease (IBD) is characterized by chronic inflammation due to an uncontrolled immune response orchestrated through, i.e. neutrophils. The basement membrane acts as a front-line defense promoting tissue integrity, where the α-3 chain of type IV collagen is solely expressed on the outermost layer of the mucosa. Detection of subclinical ulceration is crucial since early-stage IBD presents a unique window of opportunity for intervention, as the disease might become a self-sustaining process once deep inflammation becomes established. We therefore, wanted to develop a biomarker reflecting early tissue injury, aiding in the implementation of prompt treatment.

Aims & Methods

A competitive enzyme-linked immunosorbent assay quantifying a human neutrophil elastase (HNE) degraded fragment of type IV collagen α-3 chain was developed (C4A3-HNE). Dilution- and spiking recovery, inter- and intra-variability, and interference were evaluated. Acceptance criteria for technical validation were a recovery of 100% ±25 and an inter-intra variability of <15%. Commercial serum samples were purchased from ProteoGenex. Biological relevance was validated in an observational study from Odense University Hospital (OUH) and healthy controls. Groups were compared using Kruskal Wallis (Dunn‘s corrected).

Results

The technical validation of the C4A3-HNE assay demonstrated acceptable results for recovery, variation, and interference. Biological relevance was assessed in commercial IBD samples and healthy donors. C4A3-HNE was elevated in both CD and UC compared to healthy (p=0.001 and <0.0001)(AUC [95% CI]: 0.820 [0.669-0.971]; 0.875 [0.775-1.000]). The results were validated in an independent cohort of IBD patients (both p<0.0001). For UC, analysis showed that compared to patients in endoscopic remission, C4A3-HNE is elevated in patients with mild endoscopic activity, decreasing dose-dependently for moderate and severe disease (T1). Fecal calprotectin and CRP levels were also lower in IBD patients with high levels of C4A3-HNE (T1). With a cut-off value of 54.1 ng/ml, C4A3-HNE could significantly discriminate between mild and severe endoscopic disease (T1).

Conclusion

Our study demonstrates the biological and possible clinical relevance of the novel C4A3-HNE biomarker. The biomarker is elevated in patients with IBD compared with healthy, and high levels may reflect early mucosal damage in patients with UC. Furthermore, inflammatory markers were lower in IBD patients with high levels of C4A3-HNE, pointing towards high levels being indicative of early disease. C4A3-HNE may provide early detection of mucosal damage or prediction of relapse; however, further studies are required to assess the clinical validity of this biomarker.

Disclosure

MA, MP, MK, and JM are employees of Nordic Bioscience A/S. MK owns stocks in Nordic Bioscience A/S.