Fecal Calprotectin Concentration Research Articles

A-087 Stability of fecal calprotectin extracted with BÜHLMANN CALEX® Cap

Abstract Background Calprotectin, a granulocyte-derived alarmin protein, is an established noninvasive biomarker of intestinal mucosal inflammation. Fecal calprotectin testing has become the gold standard for diagnosis of inflammatory bowel diseases. The aim of this work was to determine the stability of calprotectin in stool extracts prepared with the BÜHLMANN CALEX® Cap stool preparation device. Methods The analyte stability study was carried out using CALEX® Cap extracts of human fecal left-over samples. Extraction was performed for 24 hours at room temperature and samples were aliquoted and frozen at < -20°C. The baseline calprotectin concentration was measured from thawed aliquots, which were moved to target storage temperatures (2-8 °C, 18 °C, 28 °C, and 37 °C) for up to 22 days. Five stool samples covering the measuring range of the assay were analyzed with the BÜHLMANN fCAL® turbo in four replicates. Stability evaluations were performed according to CLSI guideline EP25-A1 and EP25Ed2. Results CALEX® Cap derived extracts stored refrigerated at 2-8°C for up to 20 days and at room temperature (18-28°C) for up to 6 days demonstrated deviations from baseline of less than 20%. CALEX® Cap derived extracts stored up to 15 days at 2-8°C and up to 2 days at room temperature (18-28°C) demonstrated deviations from baseline of less than 10%. Conclusions CALEX® Cap provides a stool collection method that stabilizes fecal calprotectin concentrations for an increased processing window. This allows significant timely separation between stool collection and the actual measurement of calprotectin. This specimen stabilization provides for accurate measurements for days after sample collection and thus allows for flexibility for diagnostic laboratories.

Clinical profile and short-term outcomes of acute severe ulcerative colitis in Vietnam: insights from a resource-limited setting.

Acute severe ulcerative colitis (ASUC) is a significant complication of ulcerative colitis, affecting roughly 25% of patients and increasing the risk of colectomy and hospital mortality. While intravenous steroids are a primary treatment, only 67% of patients respond, necessitating rescue therapy for non-responders. Data on ASUC in the Vietnamese population are scarce. This study aims to provide insights into the clinical characteristics and short-term outcomes of Vietnamese patients with ASUC. We conducted a prospective case series on ASUC patients admitted to the University Medical Center in Ho Chi Minh City from January 2021 to June 2023. Steroid response was assessed using the Travis Oxford criteria. We evaluated clinical features, in-hospital steroid response rates, endoscopic remission, and colectomy rates 12 months post-hospitalization. Seventeen patients with a median age of 42 years (70.6% male) were included. The median time from symptom onset to diagnosis was six weeks, and 47.1% had a history of ulcerative colitis. Median CRP value was 75.8 mg/L, and 76.5% had fecal calprotectin concentrations above 800 µg/g. All patients had a Mayo endoscopic subscore of ≥2, with 12.5% showing deep ulcers. Eleven patients (64.7%) responded to in-hospital steroid treatment, while 6 (35.3%) required rescue therapy with infliximab or tofacitinib. After one year, 10 of 11 (90.1%) achieved mucosal healing, and no patients underwent colectomy. Corticosteroids remain the cornerstone for initial ASUC therapy, though many patients do not respond. Anti-TNF agents and tofacitinib show potential benefits for those unresponsive to steroids. This study highlights the effectiveness of corticosteroids and biologics in managing ASUC in Vietnam.

Duodenal and colonic mucosal S100A8/A9 (calprotectin) expression is increased and correlates with the severity of select histologic lesions in dogs with chronic inflammatory enteropathy

BackgroundCalprotectin, a damage-associated molecular pattern protein of the S100/calgranulin family, is a potential marker of gastrointestinal inflammation in dogs and mainly originates from activated macrophages and granulocytes. Increased calprotectin concentrations are reported in feces and serum samples from dogs with chronic inflammatory enteropathy (CIE), but mucosal calprotectin expression has not been extensively investigated in canine CIE. Thus, we aimed to evaluate gastrointestinal mucosal concentrations of calprotectin in 62 dogs (44 dogs with CIE compared to 18 healthy Beagles) using a particle-enhanced turbidimetric immunoassay method. Additionally, we assessed the relationship of gastric, duodenal, jejunal, ileal, and colonic mucosal calprotectin levels with the clinical disease severity (canine clinical inflammatory bowel disease activity index, CIBDAI), histopathologic findings, clinical outcome, and serum albumin concentrations to further evaluate the potential of calprotectin as a biomarker for CIE.ResultsMucosal calprotectin concentrations in dogs with CIE were significantly higher in the duodenum (median: 276.2 μg/g) and colon (median: 298.2 μg/g) compared to healthy controls (median: 94.3 μg/g, P = 0.0039; and median: 112.0 μg/g, P = 0.0061). Similar numerical differences in the ileum and cecum were not statistically significant, and mucosal calprotectin concentrations correlated significantly among the different gastrointestinal segments. Histologic lesion severity was linked to mucosal calprotectin concentrations for inflammatory and structural histology criteria in the duodenum and colon (all P < 0.05). Higher mucosal calprotectin levels in the duodenum and across all segments correlated with lower serum albumin concentrations (both P < 0.05); duodenal mucosal calprotectin concentrations were more than sixfold higher in hypoalbuminemic dogs (median: 1441 µg/g, n = 4) than normoalbuminemic dogs (median: 227 µg/g, n = 40). There was no significant association of mucosal calprotectin levels with CIBDAI scores or individual clinical outcomes.ConclusionsThese results show that duodenal and colonic mucosal calprotectin concentrations are increased in dogs with CIE, providing further supporting evidence for the diagnostic potential of fecal calprotectin (presumably reflecting mucosal) concentrations and in dogs with CIE. Further longitudinal research is needed to assess changes in mucosal calprotectin concentrations with clinical response to treatment vs. mucosal disease remission and to determine the clinical utility of fecal calprotectin concentrations to diagnose and monitor dogs with CIE in clinical practice.

Can Faecal Zonulin and Calprotectin Levels Be Used in the Diagnosis and Follow-Up in Infants with Milk Protein-Induced Allergic Proctocolitis?

The aim of our study was to investigate whether a 1-month-long milk-free diet results in a reduction in faecal calprotectin (FC) and faecal-zonulin-related proteins (FZRP) in children with milk-protein-induced allergic proctocolitis (MPIAP). This is a single-centre, prospective, observational cohort study involving 86 infants with MPIAP, aged 1-3 months, and 30 healthy controls of the same age. The FC and FZRP were marked using the ELISA method (IDK® Calprotectin or Zonulin ELISA Kit, Immunodiagnostik AG, Bensheim, Germany). The diagnosis of MPIAP was confirmed with an open milk challenge test. FFC and FZRP proved useful in evaluating MPIAP treatment with a milk-free diet, and the resolution of allergic symptoms and a significant (p = 0.0000) decrease in the concentrations of both biomarkers were observed after 4 weeks on the diet. The FC and FZRP concentrations were still higher than in the control group. A high variability of FC concentrations was found in all the study groups. An important limitation is the phenomenon of FZRP not being produced in all individuals, affecting one in five infants. FC and FZRP can be used to monitor the resolution of colitis in infants with MPIAP treated with a milk-free diet, indicating a slower resolution of allergic inflammation than of allergic symptoms. The diagnosis of MPIAP on the basis of FC concentrations is subject to considerable error, due to the high individual variability of this indicator. FZRP is a better parameter, but this needs further research, as these are the first determinations in infants with MPIAP.

Promotion of a Mediterranean Diet Alters Constipation Symptoms and Fecal Calprotectin in People with Parkinson's Disease: A Randomized Controlled Trial.

Parkinson's disease is associated with gastrointestinal (GI) dysfunction, including constipation symptoms and abnormal intestinal permeability and inflammation. A Mediterranean diet (MediDiet) may aid in disease management. This parallel, randomized, controlled trial in people with Parkinson's (PwP) and constipation symptoms compared a MediDiet against standard of care on change in constipation symptoms, dietary intake, and fecal zonulin and calprotectin concentrations as markers of intestinal permeability and inflammation, respectively. Participants were randomized to either standard of care for constipation (control; n = 17, 65.1 ± 2.2 years) or a MediDiet plus standard of care (n = 19, 68.8 ± 1.4 years) for 8 weeks. Constipation scores decreased with both interventions (p < 0.01), but changes from baseline were not different between groups (MediDiet, -0.5 [-1.0, 0]; control, -0.8 [-1.0, 0.2]; median [25th, 75th]; p = 0.60). The MediDiet group had a higher intake of dietary fiber at week 4 than the control group (13.1 ± 0.7 g/1000 kcal vs. 9.8 ± 0.7 g/1000 kcal; p < 0.001). No differences in fecal zonulin were observed between groups (p = 0.33); however, fecal calprotectin tended to be lower in the MediDiet group at week 8 (45.8 ± 15.1 µg/g vs. 93.9 ± 26.8 µg/g; p = 0.05). The MediDiet and standard interventions reduced constipation symptoms; however, the MediDiet provided additional benefit of increased dietary fiber intake and less intestinal inflammation.

Effectiveness of risankizumab induction and maintenance therapy for refractory Crohn’s disease: a real-world experience from a preapproval access programme and early access to medicines scheme

ObjectiveSince approval in Crohn’s disease (CD) of risankizumab, there has been widespread use. Real-world data are, however, limited and our aim is to address that gap.Design/methodWe performed a retrospective, observational...

Gut Microbiota Profiling as a Promising Tool to Detect Equine Inflammatory Bowel Disease (IBD).

Gastrointestinal disorders are common and debilitating in horses, but their diagnosis is often difficult and invasive. Fecal samples offer a non-invasive alternative to assessing the gastrointestinal health of horses by providing information about the gut microbiota and inflammation. In this study, we used 16S sequencing to compare the fecal bacterial diversity and composition of 27 healthy horses and 49 horses diagnosed with inflammatory bowel disease (IBD). We also measured fecal calprotectin concentration, a marker of intestinal inflammation, in healthy horses and horses with IBD. We found that microbiota composition differed between healthy horses and horses with IBD, although less than five percent of the variation in microbiota composition was explained by individual health status and age. Several differentially abundant bacterial taxa associated with IBD, age, or body condition were depleted from the most dominant Firmicutes phylum and enriched with the Bacteroidota phylum. An artificial neural network model predicted the probability of IBD among the test samples with 100% accuracy. Our study is the first to demonstrate the association between gut microbiota composition and chronic forms of IBD in horses and highlights the potential of using fecal samples as a non-invasive source of biomarkers for equine IBD.

Difficulties in diagnosing non-IgE-dependent gastrointestinal forms of food allergy: How informative is fecal calprotectin?

The prevalence of allergic diseases is increasing at rates corresponding to epidemic’s spread rates. Cow’s milk protein allergy (CMPA) is one of the most common food allergies in infancy. Its clinical variants remain hard-to-diagnose diseases due to their multiple clinical faces. Food allergy can develop along the pathway associated with both IgE and non-IgE, or mixed one. Non-IgEassociated variants of food allergies, due to the lack of accurate and specific laboratory markers, can cause significant difficulties in making a diagnosis. The search for new diagnostic markers continues. Faecal calprotectin, a calcium-binding leukocyte protein consisting of a complex of two monomers S100A8 and S100A9, may be one of them. Faecal calprotectin concentration is directly proportional to the number of leukocytes migrating into the intestinal wall, due to which faecal calprotectin becomes an accurate, non-invasive and sensitive indicator reflecting the level of inflammation in the intestines. Today, serum and faecal calprotectin are used as laboratory markers, and the latter, being more accessible and not critical for collection material is widely known as a diagnostic marker of inflammatory bowel diseases. Some studies suggest that faecal calprotectin may be used to diagnose cow’s milk protein allergy in young infants when other diagnostic tests are not available. Data from various studies remain contradictory. Further studies to investigate the possibilities of using faecal calprotectin as a marker of the gastrointestinal food allergy in young children is needed.

Markers of Intestinal Permeability and Inflammation in Enterally Fed Children with Cerebral Palsy.

Cerebral palsy (CP) results in non-progressive damage to the central nervous system, leading to functional disorders of the gastrointestinal tract and requiring enteral nutrition via gastrostomy in some patients. The aim of the study was to assess the impact of enteral nutrition on intestinal inflammation expressed by stool calprotectin and intestinal permeability determined by fecal zonulin and IFABP, and to determine whether CP affects these parameters. The study group consisted of 30 children with CP, fed enterally (Cerebral Palsy Enteral Nutrition-CPEN), and two reference groups: 24 children with CP, fed orally with a standard diet (CPC-Cerebral Palsy Controls) and 24 healthy children (HC-healthy controls). The differences between these groups and between the combined CP groups (CPG and CPEN + CPC) and HC were analyzed. Fecal zonulin, calprotectin, and intestinal fatty acid-binding protein 2 (IFABP2) levels were determined by ELISA. The concentrations of fecal calprotectin and zonulin were significantly higher in the CPEN group than in the CPC group (p = 0.012, p = 0.025). When comparing the CPG (n = 53) with the HC group (n = 24), statistically significant differences were observed for calprotectin (p = 0.000018, higher in the CPG) and IFABP (p = 0.021, higher in HC). Enteral nutrition was associated in our cohort with increased fecal calprotectin and zonulin. Children with cerebral palsy presented with increased fecal calprotectin but not increased intestinal permeability expressed by stool zonulin.

Noninvasive Markers of Inflammation and Protein Loss Augment Diagnosis of Pediatric Celiac Disease.

Circulating tissue transglutaminase immunoglobulin A concentration is a sensitive and specific indicator of celiac disease, but discrepancies between serologic and histologic findings occur. We hypothesized that fecal markers of inflammation and protein loss would be greater in patients with untreated celiac disease than in healthy controls. Our study aims to evaluate multiple fecal and plasma markers in celiac disease and correlate these findings with serologic and histologic findings as noninvasive means of evaluating disease activity. Participants with positive celiac serologies and controls with negative celiac serologies were prospectively enrolled before upper endoscopy. Blood, stool, and duodenal biopsies were collected. Concentrations of fecal lipocalin-2, calprotectin, and alpha-1-antitrypsin and plasma lipocalin-2 were determined. Biopsies underwent modified Marsh scoring. Significance was tested between cases and controls, modified Marsh score and tissue transglutaminase immunoglobulin A concentration. Lipocalin-2 was significantly elevated in the stool ( P = 0.006) but not the plasma of participants with positive celiac serologies. There was no significant difference in fecal calprotectin or alpha-1 antitrypsin between participants with positive celiac serologies and controls. Fecal alpha-1 antitrypsin >100 mg/dL was specific, but not sensitive for biopsy-proven celiac disease. Lipocalin-2 is elevated in the stool but not the plasma of patients with celiac disease suggesting a role of local inflammatory response. Calprotectin was not a useful marker in the diagnosis of celiac disease. While random fecal alpha-1 antitrypsin was not significantly elevated in cases compared with controls, an elevation of greater than 100 mg/dL was 90% specific for biopsy-proven celiac disease.

Real-World Outcomes of Patients Starting Intravenous and Transitioning to Subcutaneous Vedolizumab in Inflammatory Bowel Disease

BackgroundReal-world data on starting intravenous (IV) vedolizumab (VDZ) and transitioning to subcutaneous (SC) treatment in inflammatory bowel disease (IBD) are scarce.AimsTo assess treatment outcomes of patients with IBD starting IV VDZ and switching to SC VDZ in routine clinical care.MethodsAdult patients with IBD switching from IV to SC VDZ treatment between 1 March 2020 and 31 December 2021 were identified from the Swedish IBD quality register. The primary outcome was SC VDZ persistence. Secondary outcomes included clinical remission, changes in quality of life (QoL) according to EuroQual 5-Dimensions 5-Levels (EQ-5D-5L) and the Short-Health Scale (SHS) and inflammatory markers, including faecal Calprotectin (FCP).ResultsAltogether, 406 patients with IBD (Crohn's disease, n = 181; ulcerative colitis, n = 225) were identified. After a median follow-up of 30 months from starting IV VDZ treatment, the persistence rates were 98%(178/181) in Crohn's disease and 94% (211/225) in ulcerative colitis. Most patients (84%) transitioned during maintenance therapy, and the median follow-up from switch to SC VDZ was 10 months. Compared to baseline, statistically significant improvements were observed in all domains of the SHS, EQ-5D index value and visual analogue scale. Median (interquartile range) FCP concentrations (μg/g) decreased from 459 (185–1001) to 65 (26–227) in Crohn's disease (n = 45; p < 0.001) and from 646 (152–1450) to 49 (20–275) in ulcerative colitis (n = 58; p < 0.001).ConclusionInitiating IV VDZ and switching to SC treatment was associated with high persistence rates and improvements in measures of QoL and FCP. These findings are reassuring for patients who start IV VDZ and switch to SC VDZ.Graphical

Diagnostic Value of Faecal Calprotectin in Children with Chronic Gastrointestinal Disorders at Yaounde General Hospital

&amp;lt;i&amp;gt;Introduction&amp;lt;/i&amp;gt;: Chronic gastrointestinal disorders are common in children. Numerous faecal biomarkers, such as faecal calprotectin, are used in the aetiological diagnosis of these digestive disorders. The study aimed to investigate the diagnostic value of faecal calprotectin in paediatric chronic gastrointestinal disease compared with that obtained in healthy children. &amp;lt;i&amp;gt;Methodology&amp;lt;/i&amp;gt;: This was a comparative, analytical cross-sectional study from October 2022 through June 2023 at Yaoundé General Hospital. Participants were children aged between four and eighteen with chronic digestive disorders. Using a pre-established questionnaire, we collected the socio-demographic and clinical characteristics of each participant. The participants&amp;apos; faecal calprotectin was tested at the laboratory of the Yaoundé University Hospital Center by Enzyme-Linked Immunosorbent Assay (ELISA). Associations between variables were investigated by linear regression and calculation of the odds ratio (OR). The significance threshold was 5%. &amp;lt;i&amp;gt;Results&amp;lt;/i&amp;gt;: Sixty stool samples were analysed for faecal calprotectin from 30 patients and 30 healthy participants. The mean age of the population was 9.47 (± 3.35) years for patients and 10.67 (± 3.70) years for healthy participants, with a sex ratio of 1.14 for patients and 0.87 for healthy participants. The threshold value for faecal calprotectin was 2.75 µg/g, with a sensitivity of 60%, a specificity of 63%, a positive predictive value of 61.20% and a negative predictive value of 62.06%. There were no significant differences in faecal calprotectin concentrations between children with chronic gastrointestinal disorders (peptic ulcer disease: p=0.10; functional gastrointestinal disorder associated with peptic ulcer disease: p= 0.710; functional gastrointestinal disorder: p= 0.143) and healthy children. &amp;lt;i&amp;gt;Conclusion&amp;lt;/i&amp;gt;: The diagnostic value of faecal calprotectin as a biomarker in the diagnosis of chronic gastrointestinal disease was not observed in this study. However, the biological parameters assessed were measured only once, and given that their concentrations may vary over time, we recommend a subsequent longitudinal study.

Treatment success in cats with chronic enteropathy is associated with a decrease in fecal calprotectin concentrations.

Feline chronic enteropathies (FCE) are challenging to diagnose and monitor for progression and response to treatment. Fecal calprotectin might be a useful non-invasive marker to evaluate clinical endpoints of therapeutic monitoring in FCE. We evaluated fecal calprotectin concentrations in cats with FCE before and after initiation of treatment comprised of immunomodulation and/or dietary intervention. Included were 17 cats with FCE and 18 healthy controls. Clinical investigation of FCE cases included clinical severity grading (feline chronic enteropathy activity index, FCEAI) in all cats, abdominal ultrasonography in 15 cats, and gastrointestinal biopsies in 6 cats. Fecal calprotectin was measured in samples from 12 cats with FCE before treatment, all 17 FCE cats ≥6 weeks after treatment initiation, and all healthy controls. Fecal calprotectin concentrations in FCE cases before treatment (median: 61 μg/g) were significantly higher than after treatment initiation (median: 15 μg/g; p = 0.0098) and compared to controls (median: 6 μg/g; p = 0.0235) and correlated with the FCEAI scores (ρ = 0.54, p = 0.0316). Fecal calprotectin concentrations after treatment initiation were higher with more severe duodenal/proximal jejunal pathology (ρ = 0.83, p = 0.0427) and shorter intervals between sampling time points (ρ = -0.54, p = 0.0250). Relevant decreases in initially increased fecal calprotectin concentrations are seen in cats with FCE on varying treatment strategies that significantly improve or have remission of clinical signs. This supports the utility of fecal calprotectin as a surrogate biomarker to assess disease severity in FCE cases. Further studies need to evaluate fecal calprotectin concentrations longitudinally in relation to mucosal healing vs. clinical response.

Lower Diet Quality Associated with Subclinical Gastrointestinal Inflammation in Healthy United States Adults

BackgroundHigher diet quality has been associated with lower risk of developing inflammatory bowel disease, but associations between diet and gastrointestinal (GI) inflammation in healthy adults prior to disease onset are understudied. ObjectivesThe purpose of this project was to examine associations between reported dietary intake and markers of GI inflammation in a healthy adult human cohort. MethodsIn a cross-sectional observational trial of 358 healthy adults, participants completed ≤3 unannounced 24-h dietary recalls using the Automated Self-Administered Dietary Assessment Tool and a Block 2014 Food Frequency Questionnaire to assess recent and habitual intake, respectively. Those who provided a stool sample were included in this analysis. Inflammation markers from stool, including calprotectin, neopterin, and myeloperoxidase, were measured by ELISA along with LPS-binding protein from plasma. ResultsRecent and habitual fiber intake was negatively correlated with fecal calprotectin concentrations (n = 295, P = 0.011, 0.009). Habitual soluble fiber intake was also negatively correlated with calprotectin (P = 0.01). Recent and habitual legume and vegetable intake was negatively correlated with calprotectin (P = 0.013, 0.026, 0.01, 0.009). We observed an inverse correlation between recent Healthy Eating Index (HEI) scores and calprotectin concentrations (n = 295, P = 0.026). Dietary Inflammatory Index scores were calculated and positively correlated with neopterin for recent intake (n = 289, P = 0.015). When participants with clinically elevated calprotectin were excluded, recent and habitual fiber, legume, vegetable, and fruit intake were negatively correlated with calprotectin (n = 253, P = 0.00001, 0.0002, 0.045, 0.001, 0.009, 0.001, 0.004, 0.014). Recent total HEI score was inversely correlated with subclinical calprotectin (P = 0.003). ConclusionsHigher diet quality may be protective against GI inflammation even in healthy adults.This trial was registered at clinicaltrials.gov as NCT02367287.

A234 DOES FECAL CALPROTECTIN CORRELATE WITH INFLAMMATION ON ULTRASOUND IN CROHN’S DISEASE STRICTURES?

Abstract Background Fibrostenotic Crohn’s Disease (CD) is a challenging phenotype particularly due to the absence of intestinal anti-fibrotic therapies. Differentiating between strictures that are predominantly fibrotic as opposed to inflammatory remains a diagnostic dilemma. The ability to make this differentiation is critical to inform decisions for therapeutic approach. Fecal calprotectin (FC) is a stool marker reflective of intestinal inflammation. Very few studies have evaluated the relationship of FC concentration in ileal CD strictures and parameters of inflammation on intestinal ultrasound (IUS). Strictures on imaging are defined as 1) increased bowel wall thickness (BWT), 2) narrowed luminal apposition, and 3) pre-stenotic dilation (PSD). BWT and hyperemia (color Doppler signal (CDS)) are the most sensitive markers for CD inflammation on IUS. It is predicted that FC will match CDS in ileal strictures, similar to non-stricture phenotypes. Aims We aim to correlate FC levels with IUS inflammation of ileal CD strictures. Methods We performed a retrospective cohort pilot study exploring the relationship between FC levels and IUS inflammatory parameters in ileal strictures. FC levels were obtained ≤ 60 days of index IUS in fibrostenotic ileal CD patients. Individuals who underwent medication changes or experienced a clinical flare during this period were excluded. Inflammation was measured as BWT and CDS using a modified Limberg (ML) score. Pearson correlation for continuous variables, Spearman rank correlation and a Kruskal-Wallis test for FC and Limberg scale were completed. Results A total of 25 fecal samples were obtained from 17 patients with ileal strictures (47% male, median age 59 years (range 18-76)) were assessed. Median FC concentrations was 204.9 ug/g, IQR: 250.4. Median ileal stricture BWT was 7.0 mm (range 3.0–10.0). 40% (10/25) had ML1 (short chains in bowel), 32% (8/25) ML2 (long chains in bowel), and 28% (7/25) ML3 (long chains and perienteric fat). There was no correlation between FC and BWT (r= .02, p = 0.92), nor FC with ML scores (r=0.20, p= 0.25). In those with ML1, median FC was 232.4, while those with ML2 or 3, had a FC of 155.6 and 469.7, respectively. FC values were significantly different between the ML scores, pampersand:003C0.0001. Conclusions FC levels were not correlated with inflammatory parameters as seen on IUS in ileal CD. This unexpected finding may be due to ML2 scores having lower FC than anticipated, and small sample size. Other imaging factors such as loss of wall stratification need to be taken into account, and are perhaps more reflective of inflammation than BWT and CDS. This study provides the initial data to assess accuracy of FC and hyperemia of ileal CD strictures on IUS compared to histologic measures of inflammation on resected specimens. Funding Agencies None

A green tea extract confection decreases circulating endotoxin and fasting glucose by improving gut barrier function but without affecting systemic inflammation: A double-blind, placebo-controlled randomized trial in healthy adults and adults with metabolic syndrome

Anti-inflammatory activities of catechin-rich green tea extract (GTE) in obese rodents protect against metabolic endotoxemia by decreasing intestinal permeability and absorption of gut-derived endotoxin. However, translation to human health has not been established. We hypothesized that GTE would reduce endotoxemia by decreasing gut permeability and intestinal and systemic inflammation in persons with metabolic syndrome (MetS) compared with healthy persons. A randomized, double-blind, placebo-controlled, crossover trial in healthy adults (n = 19, 34 ± 2 years) and adults with MetS (n = 21, 40 ± 3 years) examined 4-week administration of a decaffeinated GTE confection (890 mg/d total catechins) on serum endotoxin, intestinal permeability, gut and systemic inflammation, and cardiometabolic parameters. Compared with the placebo, the GTE confection decreased serum endotoxin (P = .023) in both healthy persons and those with MetS, while increasing concentrations of circulating catechins (P < .0001) and γ-valerolactones (P = .0001). Fecal calprotectin (P = .029) and myeloperoxidase (P = .048) concentrations were decreased by GTE regardless of health status. Following the ingestion of gut permeability probes, urinary lactose/mannitol (P = .043) but not sucralose/erythritol (P > .05) was decreased by GTE regardless of health status. No between-treatment differences (P > .05) were observed for plasma aminotransferases, blood pressure, plasma lipids, or body mass nor were plasma tumor necrosis factor-α, interleukin-6, or the ratio of lipopolysaccharide-binding protein/soluble cluster of differentiation-14 affected. However, fasting glucose in both study groups was decreased (P = .029) by the GTE confection compared with within-treatment arm baseline concentrations. These findings demonstrate that catechin-rich GTE is effective to decrease circulating endotoxin and improve glycemic control in healthy adults and those with MetS, likely by reducing gut inflammation and small intestinal permeability but without affecting systemic inflammation.

FROM RESISTANCE TO RESPONSE: 52 WEEKS OF SUBCUTANEOUS INFLIXIMAB IN REFRACTORY CROHN'S DISEASE PATIENTS AFTER THE MULTIPLE TREATMENT FAILURES

Abstract BACKGROUND Infliximab (IFX), an anti-TNFα monoclonal antibody, has been utilized since the late 1990s as an effective therapeutic agent for the treatment of Crohn's disease (CD). Since 2020, subcutaneous IFX (IFX-SC) has been available for treating CD. This study aimed to conduct a 52-week observation of IFX-SC treatment in refractory CD patients who had failed on at least two previous lines of biologic therapy patients. MATERIALS AND METHODS The study included 32 patients diagnosed with CD who had failed on 2 to 7 previous lines of biological therapy. Observed cohort was monitored at weeks W0, W4, W14, W30, and W52, recording Harvey-Bradshaw Index (HBI) , C-reactive protein (CRP) and fecal calprotectin (FC) concentrations, trough infliximab (TL-IFX) and anti-infliximab (anti-IFX) serum levels. Endoscopic, ultrasonographic and magnetic resonance disease scores (SES-CD, IUS and MaRIA) were determined at baseline and W52. RESULTS 52-week persistence on IFX-SC treatment was recorded in 18 out of 32 patients (56.3%). A significant decrease of HBI (P &amp;lt;0 .0001), CRP (P =0 .0035), FC (P =0.0012), SES-CD (P =0.013), IUS (P =0.0034) and MaRIA (P =0.0261) was observed. TL IFX increased significantly (.0073), and median TL-IFX levels reached 19.75 μg/mL at W52. During the therapy, 8 out of 16 initially anti-IFX positive individuals seroconverted to negative anti-IFX (50 %); no new sensitization to IFX was recorded in the cohort. None of the patients treated with IFX-SC in W52 needed concomitant immune-modifying treatment. Baseline clinical, laboratory, and imaging markers did not demonstrate any predictive value for IFX-SC treatment failure, except for baseline high levels of anti-IFX (P = &amp;lt;0.0001). CONCLUSION In the cohort of refractory CD patients, over half achieved one-year treatment persistence on IFX-SC, displaying a highly favorable trend in all disease activity markers. The IFX-SC treatment appears to be effective and safe; however, further research is needed to identify potential predictors of therapeutic responsiveness. Acknowledgement: This work was supported by the IBD-COMFORT Foundation

P348 Increased pre-treatment faecal calprotectin concentration predicts resistance to ustekinumab induction in ulcerative colitis

Abstract Background Rates of resistance to advanced therapy remain high in ulcerative colitis (UC). Pre-treatment predictors of poor outcomes would provide valuable information for treating clinicians so other therapies could be given or early treatment switches could be considered if response is inadequate. We investigated whether baseline, pre-treatment faecal calprotectin (FCP) can predict resistance to ustekinumab. Methods Clinical outcomes at week 8, including clinical remission, endoscopic healing and mucosal healing were determined in patients enrolled in the UNIFI phase 3 placebo-controlled trial program, investigating the efficacy of ustekinumab for moderate-to-severe UC (GSE206285), in whom FCP concentrations were available at baseline, prior to initiation of treatment. Clinical outcomes were defined in patients with FCP &amp;lt; 250mcg/g, 250 – 999mcg/g, 1000 – 1999mcg/g and &amp;gt;= 2000mcg/g. Chi-squared test was used to assess statistical significance. Area under the receiver operating characteristics curve (AUROC) analyses were used to determine the ability of faecal calprotectin level to predict treatment resistance. Analyses were performed using R 4.2.3 (Vienna, Austria) and GraphPad Prism 10.0.3 (Massachusetts, United States). Results Outcome data and linked faecal calprotectin levels were available for 340 patients. FCP values ranged from 15 – 25249mcg/g. The median FCP value was 1402mcg/g (interquartile range: 600.8 – 2772.0mcg/g). In general, all clinical outcome measures were progressively worse with increasing FCP concentrations. For the respective FCP cut-offs, 22.0%, 19.3%, 11.3% and 6.7% achieved clinical remission; 39.0%, 24.1%, 20.6% and 16.0% achieved endoscopic healing; and 29.3%, 16.9%, 15.5% and 7.6% achieved mucosal healing (Figure 1). ROC analyses revealed that pre-treatment FCP predicts resistance to ustekinumab therapy for all stated outcomes, including clinical remission (AUROC: 0.66, P=0.001), endoscopic healing (AUROC: 0.63, P=0.0013) and mucosal healing (AUROC: 0.65, P=0.0005). Conclusion Increasing concentrations of pre-treatment FCP predicts resistance to ustekinumab therapy in moderate-to-severe UC. Patients with FCP &amp;gt;= 2000mcg/g were significantly less likely than those with FCP &amp;lt;1000 mcg/g to achieve clinical remission or mucosal healing. Since neutrophils are the main producers of FCP, these data build on other emerging data indicating that excessive accumulation of mucosal neutrophils is associated with treatment resistance in IBD.

P476 Correlation between fecal calprotectin and inflammation on ultrasound in fibrostenotic Crohn’s Disease

Abstract Background Fibrostenotic Crohn’s Disease (CD) is a challenging phenotype particularly due to the absence of intestinal anti-fibrotic therapies. Differentiating between strictures that are predominantly fibrotic versus inflammatory remains a diagnostic dilemma. The ability to make this differentiation is critical to inform therapeutic decisions. Fecal calprotectin (FC) is a stool marker reflective of intestinal inflammation. Very few studies have evaluated the relationship of FC concentration in ileal CD strictures and parameters of inflammation on intestinal ultrasound (IUS). Strictures on imaging are defined as 1) increased bowel wall thickness (BWT), 2) narrowed luminal apposition, and 3) pre-stenotic dilation (PSD). BWT and hyperemia (color Doppler signal (CDS)) are the most sensitive markers for CD inflammation on IUS. It is predicted that FC will match CDS in ileal strictures, similar to non-stricture phenotypes. We aim to correlate FC levels with IUS inflammation of ileal CD strictures. Methods We performed a retrospective cohort pilot study exploring the relationship between FC levels and IUS inflammatory parameters in ileal strictures. FC levels were obtained ≤ 60 days of index IUS in fibrostenotic ileal CD patients. Individuals who underwent medication changes or experienced a clinical flare during this period were excluded. Inflammation was measured as BWT and CDS using a modified Limberg (ML) score. Pearson correlation for continuous variables, Spearman rank correlation and a Kruskal-Wallis test for FC and Limberg scale were completed. Results A total of 25 fecal samples were obtained from 17 patients with ileal strictures (47% male, median age 59 years (range 18-76)) were assessed. Median FC concentrations was 204.9 ug/g, IQR: 250.4. Median ileal stricture BWT was 7.0 mm (range 3.0–10.0). 40% (10/25) had ML1 (short chains in bowel), 32% (8/25) ML2 (long chains in bowel), and 28% (7/25) ML3 (long chains and perienteric fat). There was no correlation between FC and BWT (r=0.02, p=0.92), nor FC with ML scores (r=0.20, p=0.25). In those with ML1, median FC was 232.4, while those with ML2 or 3, had a FC of 155.6 and 469.7, respectively. FC values were significantly different between the ML scores, p&amp;lt;0.0001. Conclusion FC levels were not correlated with inflammatory parameters as seen on IUS in ileal CD. This unexpected finding may be due to ML2 scores having lower FC than anticipated, and small sample size. Other imaging factors such as loss of wall stratification need to be taken into account, and are perhaps more reflective of inflammation than BWT and CDS. This study provides the initial data to assess accuracy of FC and hyperemia of ileal CD strictures on IUS compared to histologic measures of inflammation on resected specimens.

P430 The influence of persistent organ damage on IFX pharmacokinetic modeling and disease progression assessment: findings from a prospective real-world study in inflammatory bowel disease patients

Abstract Background Effective management of inflammatory bowel disease (IBD) relies on a comprehensive understanding of infliximab (IFX) pharmacokinetics (PK). This study's primary goal was to develop a robust PK model, identifying key covariates influencing IFX clearance (CL), while concurrently evaluating the risk of disease progression during the maintenance phase of IBD treatment. Methods The multicenter, prospective, real-world DIRECT study was conducted in several care centers, which included 369 IBD patients in the maintenance phase of IFX therapy. A two-compartment population PK model was used to determine IFX CL and covariates. Logistic and Cox regressions were applied to elucidate the associations between disease progression and covariates embedded in the PK model. Results The PK model included the contributions of weight, albumin, antidrug antibody (ADA), and fecal calprotectin (FC). On average, higher ADA, FC concentration and weight, and lower albumin concentration resulted in higher IFX CL. In the multivariate regression analyses, FC levels influenced the odds of disease progression in all its different definitions, when adjusted for several confounding factors (Fig. 1). Additionally, alongside FC, both IFX and C-reactive protein demonstrated a significant impact on the temporal aspect of disease progression. Conclusion In this 2-year prospective real-world study, readily available clinical covariates, notably FC, significantly impacted IFX availability in IBD patients. We demonstrated that persistent gut damage, as mirrored by FC, substantially influenced IFX clearance. Importantly, FC emerged as a pivotal determinant, not only of IFX pharmacokinetics but also of the progression of the underlying disease. These findings underscore the imperative need to integrate FC into forthcoming IFX pharmacokinetic models, amplifying its clinical significance.