Low Fecal Calprotectin Research Articles

DOP010 Optimizing the switch from escalated intravenous to subcutaneous infliximab: a population pharmacokinetics–pharmacodynamics study

Abstract Background The standard subcutaneous (SC) infliximab (IFX) of 120 mg bi-weekly (Q2W) has shown non-inferior pharmacokinetics (PK) and comparable efficacy to the intravenous (IV) IFX of 5 mg/kg Q8W in clinical trials. However, it remains unclear whether patients on escalated IV dosing regimens can transition to standard SC dosing without losing therapeutic response. This study aims to elucidate the dose–exposure–response relationship during IV-to-SC switching of IFX in patients with Crohn’s disease (CD) and ulcerative colitis (UC) through population pharmacokinetics–pharmacodynamics (popPK–PD) modelling and simulation. Methods Data were collected from healthy volunteers in two single-dose Phase I studies ([1]; NCT03446976) and patients with IBD in a two-part Phase I study (NCT02883452). In patients with IBD, frequent PK sampling was conducted during switching from 5 mg/kg IV IFX to Q2W SC IFX injections of 120/180/240 mg in Part 1 and 120/240 mg in Part 2. Faecal calprotectin (FC) was measured in patients at baseline, week (w)2, w6, and Q8W thereafter until w54. Endoscopic remission (ER) was assessed at screening, w22/30, and w54. We performed popPK–PD modelling and simulation (n=1000) using NONMEM to evaluate post-switch FC time courses and probabilities of ER. Results A total of 253 healthy volunteers and 179 patients (101 CD, 78 UC) contributed 7351 IFX and 1201 FC concentrations. IFX clearance increased with decreasing serum albumin, increasing body weight, and presence of neutralizing antibodies. FC levels decreased when overall IFX exposure (not just IFX trough concentrations) increased. Lower FC at w14 were associated with increased probabilities of ER in patients with UC, but not CD. Simulations showed that the standard IV-to-SC switch at w6 of IFX therapy further decreases FC and results in a significantly higher probability of ER at w22/30 (54% if no switch vs 63% if switch) (Figure 1). Simulations also showed that patients on escalated Q6W/Q8W IV maintenance regimens can switch to 120 mg Q2W SC infliximab without FC increasing (Figure 2A). Patients on Q4W IV infliximab require SC dose escalation to either 120 mg QW or 240 mg Q2W to avoid an increase in FC (Figure 2B). Conclusion Infliximab trough concentrations are only a surrogate for therapeutic response, with overall infliximab exposure being the true driver. Therefore, the higher trough concentrations on standard SC dosing are needed to compensate for the lower SC peak concentrations. Standard SC dosing is superior to standard IV IFX dosing as evidenced by lower FC and higher ER rates (in patients with UC). Patients on Q6W and Q8W IV regimens can switch to standard SC IFX without an increase in FC.

P1323 Differential Microbiome Responses to the Crohn’s Disease Exclusion Diet in Pediatric vs. Adult Populations: Insights from Randomized Controlled Trials

Abstract Background The Crohn’s Disease (CD) Exclusion Diet (CDED) is a recognized dietary therapy for managing mild-to-moderate CD in children and adults1,2. This study aimed to compare the effects of CDED on the microbiome in children and adults, based on randomized controlled trials (RCTs) in both cohorts1,2. Methods We analyzed fecal samples from 2 RCTs; one comparing CDED to exclusive enteral nutrition in children over 12 weeks (n:W0 = 69, n:W06 = 57, n:W12 = 52), and the other examining CDED with or without partial enteral nutrition in adults over 24 weeks (n:W0 = 35, n:W06 = 32, n;W12 = 30, n:W24 = 26). We compared the pediatric CDED group with both adult groups, all with mild-to-moderate disease and active inflammation. The V4-V5 region of the 16S rRNA gene was amplified and sequenced, with reads processed through QIIME2 and the SILVA database. Associations between the microbiome, short-term clinical remission and fecal calprotectin (FC) were analyzed using logistic regression, Poisson Principal Component Analysis, Wilcoxon tests, ANOVA, and subsampling ranking forward selection. Results Pediatric patients had higher baseline alpha diversity, which significantly increased by week 12 and was higher in remission compared to adults, who showed a similar but nonsignificant trend. In both pediatric and adult cohorts, baseline Haemophilus abundance was significantly associated with reduced probability of sustained remission (measured at weeks 6 and 12 [pediatric], and 12 and 24 [adults]). Ruminococcus levels increased from baseline to week 6 in patients who did not achieve remission across both cohorts. At week 12, pediatric patients had more taxa associated with achieving remission, whereas adults showed more taxa linked to non-remission. Prevotella was associated with non-remission in both pediatric and adult cohorts, while Akkermansia was linked to non-remission in adults only. By weeks 6 and 12, both cohorts showed increases in Oscillibacter and decreases in Haemophilus.In adults, Alistipes increased over time and was associated with milder disease at baseline for both cohorts. Higher baseline FC in children suggested more severe initial disease. An increase in Firmicutes was associated with lower FC in both cohorts, indicating beneficial microbiome shift in response to CDED. In patients with more severe disease, higher Proteobacteria prevalence was observed, with a stronger difference observed in pediatric than in adult. Conclusion These finding suggest that key microbiome could serve as biomarkers for predicting responses to CDED, enabling more personalized dietary management for CD. Microbial shifts associated with reduced inflammation after CDED, highlight the potential for tailored dietary approaches for both children and adults.

Extracorporeal Photopheresis with 5-Aminolevulinic Acid in Crohn's Disease-A First-in-Human Phase I/II Study.

Background/Objectives: With the increasing prevalence of Crohn's disease (CD), treatment options for patients who fail conventional and advanced therapy are highly needed. Therefore, we explored the safety and efficacy of extracorporeal photopheresis (ECP) using 5-aminolevulinic acid (ALA) and blue light (405 nm). Methods: Patients with active CD who failed or were intolerant to biological therapy were eligible. Mononuclear cells (90 mL) were collected from each patient using a Spectra Optia® apheresis system and diluted with 100 mL of 0.9% sodium chloride in a collection bag. The cells were incubated with ALA at a concentration of 3 millimolar (mM) for 60 min ex vivo and illumination with an LED blue light (405 nm) source (BLUE-PIT®) before reinfusion to the patient. Recording of vital signs and adverse events were regularly performed. At week 13, we assessed the patients with colonoscopy, the Harvey Bradshaw Index (HBI), the Inflammatory Bowel disease Health Related Quality of Life Questionnaire, and the measurement of serum C-reactive protein and fecal calprotectin (FC) levels. Biopsies of the intestines were taken for immunohistochemistry. Results: Seven patients were included. Four patients completed the treatments, with a total of 24 treatments. Three of the four patients achieved a favorable response, including a lower HBI, lower FC levels, and/or endoscopic improvement. No significant adverse events were observed. The remaining three patients received only one, three, or five treatments due to technical difficulties, medical reasons, or the withdrawal of informed consent. Conclusions: ALA-based ECP appears safe and seems to give some clinical improvement for the patients with active CD who failed to respond to conventional and advanced therapies.

Impact of Coffee Consumption on Subjective Perception and Inflammatory Markers in Patients with Inflammatory Bowel Diseases.

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic conditions marked by persistent inflammation, impacting patients' quality of life. This study assessed differences in coffee consumption between CD and UC patients and its potential effects on the subjective perception and objective changes in inflammation markers in these two categories of patients. Using questionnaires, coffee consumption patterns, and perceived symptom effects were evaluated. Biological samples were collected to measure the following inflammatory markers: leukocytes, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and fecal calprotectin (FC). Among 148 patients, 60% reported regular coffee consumption, with no significant difference between CD and UC patients. While 45.93% perceived no impact on symptoms, 48% of those reporting exacerbation continued their regular coffee consumption. FC values were significantly lower in coffee consumers than in non-consumers (p < 0.05), particularly in those consuming natural coffee (p < 0.001), and the case was observed for UC patients (p < 0.05). No significant differences were observed in other inflammatory markers, regardless of coffee type, frequency, or milk addition. This study highlights the commonality of coffee consumption among IBD patients and the association of lower FC levels with coffee consumption, especially in UC patients, suggesting that coffee may influence intestinal inflammatory responses.

Evaluating the Efficacy of Fecal Immunochemical Test, Fecal Calprotectin, and Serum C-Reactive Protein in Diagnosing Patients With Chronic Lower Gastrointestinal Symptoms.

Accurate early detection of ileocolonic lesions in patients with chronic lower gastrointestinal symptoms (LGISs) is often difficult due to the rarity of early-stage alarm signs. This study assesses the effectiveness of noninvasive blood and stool biomarkers in diagnosing ileocolonic lesions in patients with chronic LGISs undergoing colonoscopy. We conducted a prospective study between April 2020 and July 2022 involving patients with LGISs lasting a month or more. Before colonoscopy, we gathered clinical data, blood samples for C-reactive protein (CRP) and stool samples for fecal immunochemical test (FIT) and fecal calprotectin (FC) analysis. Of 922 participants analyzed (average age 62 years, 37% male), 130 (14.1%) had significant colonoscopy findings, including cancer, advanced adenoma, and inflammatory conditions. Test effectiveness showed an area under the curve of 0.630 for alarm features, 0.643 for CRP, 0.781 for FIT, and 0.667 for FC. Combining stool tests with alarm features improved diagnostic precision. Those without alarm features had a high negative predictive value of 0.97 with low threshold FIT and FC, missing minimal significant lesions, and no cancer. For patients with alarm features, dual high-cutoff test positivity showed a positive predictive value of 0.67. Adding CRP to fecal tests did not enhance accuracy. FIT and FC are valuable in evaluating LGISs. Negative results at low cutoffs can delay colonoscopy in limited resource settings while positive results at dual high cutoffs substantiate the need for the procedure.

Elevated fecal calprotectin is associated with gut microbial dysbiosis, altered serum markers and clinical outcomes in older individuals

Fecal calprotectin is an established marker of gut inflammation in inflammatory bowel disease (IBD). Elevated levels of fecal calprotectin as well as gut microbial dysbiosis have also been observed in other clinical conditions. However, systemic and multi-omics alterations linked to elevated fecal calprotectin in older individuals remain unclear. This study comprehensively investigated the relationship between fecal calprotectin levels, gut microbiome composition, serum inflammation and targeted metabolomics markers, and relevant lifestyle and medical data in a large sample of older individuals (n = 735; mean age ± SD: 68.7 ± 6.3) from the TREND cohort study. Low (0–50 μg/g; n = 602), moderate (> 50–100 μg/g; n = 64) and high (> 100 μg/g; n = 62) fecal calprotectin groups were stratified. Several pro-inflammatory gut microbial genera were significantly increased and short-chain fatty acid producing genera were decreased in high vs. low calprotectin groups. In serum, IL-17C, CCL19 and the toxic metabolite indoxyl sulfate were increased in high vs. low fecal calprotectin groups. These changes were partially mediated by the gut microbiota. Moreover, the high fecal calprotectin group showed increased BMI and a higher disease prevalence of heart attack and obesity. Our findings contribute to the understanding of fecal calprotectin as a marker of gut dysbiosis and its broader systemic and clinical implications in older individuals.

Fecal Calprotectin in Patients with Crohn's Disease: A Study Based on the History of Bowel Resection and Location of Disease.

Fecal calprotectin (FC) is commonly used to assess Crohn's disease (CD) activity. However, standardized cut-off values accounting for bowel resection history and disease location are lacking. In this study, we analyzed data from patients with CD who underwent magnetic resonance enterography, ileocolonoscopy, and FC measurements from January 2017 to December 2018. In 267 cases from 254 patients, the FC levels in the 'operated' patients were higher when the disease was active compared with those who were in the remission group (178 vs. 54.7 μg/g; p < 0.001), and similar findings were obtained for the 'non-operated' patients (449.5 vs. 40.95 μg/g; p < 0.001). The FC levels differed significantly according to the location of inflammation, with lower levels in the small bowel compared to those in the colon. The FC cut-off levels of 70.8 μg/g and 142.0 μg/g were considered optimal for predicting active disease for operated and non-operated patients, respectively. The corresponding FC cut-off levels of 70.8 μg/g and 65.0 μg/g were observed for patients with disease only in the small bowel. In conclusion, different FC cut-off values would be applicable to patients with CD based on their bowel resection history and disease location. Tight control with a lower FC target may benefit those with a history of bowel resection or small-bowel-only disease.

Positive relationship between plant diversity dietary patterns and disease activity in Australian adults with Inflammatory Bowel Disease

Diet is implicated in the development of Inflammatory Bowel Disease (IBD). However, the role of diet in reducing inflammation and managing prevalent disease is unclear (1–3). Previous studies have analysed the relationship between dietary patterns and occurrence of flares or symptoms, but not disease activity or inflammation (4–5). It is important to explore the role of habitual diet in management of IBD to provide targeted dietary recommendations. We explored the relationship between dietary intake with disease activity and inflammation in an Australian adult cohort with and without IBD. We analysed dietary and clinical data from the Australian IBD Microbiome (AIM) study. AIM is a prospective longitudinal cohort study of adults and children with Crohn’s Disease (CD), Ulcerative colitis (UC) and healthy controls (HC). Habitual dietary intake of food groups, fibre, polyphenols and fermented foods was collected by merging dietary data from 3-day food records and food frequency questionnaires with PhenolExplorer and the Australian Fibre Categories Database. Dietary patterns were explored using Principal Component Analysis (PCA) and cluster analysis (CA) in IBM SPSS Statistics (V29). Associations between dietary intake, clinical disease activity categorised as remission or active, and faecal calprotectin (FCAL) were explored in adult participants. A total of 412 participants (IBD = 223, HC = 189) were included. FCAL data was available for 211 participants (HC = 100, CD = 49, UC = 62). Median (IQR) FCAL at baseline was 20 (20) mg/kg for HC and 33 (127) mg/kg for IBD, indicating clinically irrelevant inflammation (FCAL &gt;50mg/kg = clinical inflammation). PCA identified 7 distinct dietary patterns for adults with IBD. A dietary pattern of high plant diversity was associated with active CD. In the total IBD cohort, low association to a 'Prudent’ pattern was positively associated with low FCAL, and high association to a 'Meat-eaters’ dietary pattern was positively associated with moderate FCAL. CA revealed 3 distinct clusters amongst participants with IBD. No significant difference between diet cluster and disease activity or FCAL was seen. There were no significant differences in intake of fibre or polyphenols between remission vs active disease in participants with IBD. A significant difference between total, soluble and insoluble fibre and FCAL categories was seen with a higher fibre intake associated with lower FCAL. Higher plant-diversity and 'Prudent’ dietary patterns are associated with active disease and higher FCAL in Australian adults with IBD. Reverse causality cannot be ruled out, with analysis of larger cohorts and clinical trial data needed to clarify this.

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

İnflamatuvar Bağırsak Hastalığında Tanı Anındaki Fekal Kalprotektin Komplikasyon Varlığını Gösterebilir

Aim: We aimed to investigate the relationship between the presence of complications at the time of diagnosis or during follow-up and fecal calprotectin in patients with inflammatory bowel disease. Materials and Methods: Fecal calprotectin level was studied by the chromatographic lateral flow immunoassay method. Results: A total of 76 patients, 26 (34%) with Crohn's disease and 50 (66%) with ulcerative colitis, were included in the study. At the time of diagnosis and during follow-up, complications were observed in 17 (22%) and 20 (26%) patients, respectively. At the time of diagnosis, fecal calprotectin level was low (&amp;lt;50 mg/kg) in 26 (34%) patients, borderline (50-100 mg/kg) in 16 (21%) patients, and high (&amp;gt;100 mg/kg) in 34 (45%) patients. Hemoglobin and albumin levels were lower (p=0.013, p=0.012, respectively), and platelet count, eryrocyte sedimentation rate, and C-reactive protein levels were higher (p&amp;lt;0.001, p=0.004, p&amp;lt;0.001, respectively) in patients with high fecal calprotectin level than patients with low fecal calprotectin level. At the time of diagnosis and during follow-up, complications were higher in patients with high fecal calprotectin level than patients with low and borderline fecal calprotectin levels (p=0.001). The risk of developing complications was found to be 26 times higher at the time of diagnosis in patients with fecal calprotectin level &amp;gt;100 µg/g than patients with fecal calprotectin level below this value and 8 times higher during follow-up (p=0.006, p=0.015, respectively). Conclusion: The use of fecal calprotectin level together with tests showing acute inflammation in inflammatory bowel disease may predict the development of complications.

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.

P1102 Adherence to a Mediterranean dietary pattern in patients with Crohn's disease in remission is associated with lower fecal calprotectin levels

Abstract Background The Mediterranean Diet (MD) was recently found to be beneficial for Crohn’s Disease CD patients in various stages of the disease. The MD emphasizes the intake of foods that are fiber-rich and high in polyphenols, along with avoidance of ultra-processed foods (UPF) and a low intake of red meat. Previous data show that these dietary patterns could promote gut health and mucosal healing. However, little is known about the overall adherence to the MD and its association with biochemical activity in CD patients in remission. Therefore, we aimed to assess overall adherence to the MD and to investigate the association between adherence to the MD and fecal calprotectin (FC) levels in patients with CD in clinical remission and fecal biochemical inactivity. Methods A cross-sectional analysis of a prospectively maintained database of patients with CD in clinical remission [Harvey-Bradshaw Index (HBI)&amp;lt;5] and fecal biochemical inactivity (FC &amp;lt;250µg/g). FC levels of ≤150µg/g was further categorized as significant biochemical inactivity. Patients were assessed for their medical status, clinical and biochemical disease activity, and nutritional intake by using a Food Frequency Questionnaire (FFQ). The Israeli Mediterranean dietary screener (I-MEDAS) was used to assess adherence to the MD. A positive score for each food component was assigned when a specific cut-off criterion was met. For overall adherence to the MD, the median score of the study sample was used as a cut-off for the classification of “adherence” or “non-adherence”. Results A total of 88 patients were included in this analysis. A high proportion of patients qualified for a positive score for low consumption of butter and margarine (96.6%), salty snacks (94.3%), and savory pastries (83.0%), while a low proportion of patients qualified for a positive score for high intake of whole grains (8.0%), fish (20.9%), fruit (9.1%), and legumes (28.4%) (Figure 1). Twenty-nine patients (32.9%) were adherent to the MD. This group of patients had higher rates of significant biochemical inactivity (i.e., FC≤150µg/g), compared to non-adherent patients (96.6% vs. 79.7% respectively, p=0.036) and lower occurrence of soft/liquid stool (p=0.044). Furthermore, low intake of savory pastries and red/processed meat was associated with significant biochemical inactivity [p=0.026 and p=0.020, respectively. Conclusion Overall adherence to the MD among patients with CD in clinical remission and biochemical inactivity is relatively low, with a low intake of beneficial food groups on one hand, and a low intake of UPF on the other hand. Adherence to the MD was associated with lower FC levels. Future studies should examine the long-term effects of the MD on the maintenance of clinical and biochemical remission.

Infliximab: a single-centre, prospective, observational evaluation of TDM data in patients with IBD

ObjectivesTherapeutic drug monitoring of infliximab (IFX) is important to optimise treatment of inflammatory bowel disease (IBD). A recent IBD consensus statement recommends targeting trough serum concentrations of >3 μg/mL, higher...

Therapeutic drug monitoring of methotrexate in patients with Crohn's disease.

Therapeutic drug monitoring (TDM) has the potential to improve efficacy and diminish side effects. Measuring methotrexate-polyglutamate (MTX-PG) in erythrocytes might enable TDM for methotrexate in patients with Crohn's disease (CD). To investigate the relationship between MTX-PGs and methotrexate drug survival, efficacy and toxicity METHODS: In a multicentre prospective cohort study, patients with CD starting subcutaneous methotrexate without biologics were included and followed for 12 months. Primary outcome was subcutaneous methotrexate discontinuation or requirement for step-up therapy. Secondary outcomes included faecal calprotectin (FCP), Harvey Bradshaw Index (HBI), hepatotoxicity and gastrointestinal intolerance. Erythrocyte MTX-PGs were analysed at weeks 8, 12, 24 and 52 or upon treatment discontinuation. We included 80 patients with CD (mean age 55 ± 13y, 35% male) with a median FCP of 268 μg/g (IQR 73-480). After the 12-month visit, 21 patients (26%) were still on subcutaneous methotrexate monotherapy. Twenty-one patients stopped because of disease activity, 29 because of toxicity, and four for both reasons. Five patients ended study participation or stopped methotrexate for another reason. A higher MTX-PG3 concentration was associated with a higher rate of methotrexate drug survival (HR 0.86, 95% CI 0.75-0.99), lower FCP (β -3.7, SE 1.3, p < 0.01) and with biochemical response (FCP ≤250 if baseline >250 μg/g; OR 1.1, 95% CI 1.0-1.3). Higher MTX-PGs were associated with less gastrointestinal intolerance. There was no robust association between MTX-PGs and HBI or hepatotoxicity. Higher MTX-PG3 concentrations are related to better methotrexate drug survival and decreased FCP levels. Therefore, MTX-PG3 could be used for TDM if a target concentration can be established.

A77 THE ASSOCIATIONS OF OBJECTIVELY ASSESSED SEDENTARY TIME AND STEP COUNT ON ULCERATIVE COLITIS OUTCOMES

Abstract Background Physical activity has been associated with positive health outcomes in those with Ulcerative Colitis (UC). The extent to which other more prominent behaviours occurring throughout the 24-hour day (i.e., sitting, standing, lying down, and stepping) are associated with UC outcomes is unknown. Purpose The purpose of this study was to explore whether objectively measured time spent sitting, lying down, standing, and stepping were associated with Total Mayo score (TMS), fecal calprotectin (FCP), and C-reactive protein (CRP) in patients with UC. Method Patients were recruited from the Foothills Medical Center in Calgary, Alberta and were given activPALTM accelerometers (PAL Technologies Limited, Glasgow, UK) to wear on their thigh for 7 days. Step count, sitting time, standing time, and time lying down (excluding sleep) were recorded for a minimum of 4 days, including at least one day on the weekend. TMS was used to determine disease activity and patients were categorized into normal/mild (TMS score &amp;lt;6) or moderate/severe (TMS score 6). FCP, a marker of gut inflammation, was measured using stool samples. Blood samples were collected to measure serum CRP, a marker of systemic inflammation. Univariate analysis of covariance (ANCOVA) was used to evaluate associations between the activPALTM daily activity variables, TMS, FCP (&amp;lt; or &amp;gt;250ug/g) and CRP (&amp;lt; or &amp;gt; 5 mg/L). Analyses were controlled for age, sex, body mass index (BMI), and antibiotic use. Result(s) Patients (N=29; 15 male, 14 female) were on average 38 years of age (SD=12.1). The average BMI was 26.2 kg/m2 (SD=3.2). Based on TMS, 14 had moderate/severe disease activity and 16 had normal/mild disease activity. Average CRP was 2.16 mg/L (SD=2.49) while the mean FCP was 954.5 ug/g (SD=1427.7). Patients recorded an average of 8,137 steps (SD=3,051) per day. Average standing time was 240 minutes (SD=84) per day, sitting time was 503 minutes (SD=131) per day, and time spent lying down was 527 minutes (SD=111) per day. FCP was negatively associated with step count (D=-2,134 steps, 95% CI: -4,360 to 93, p=0.06). Patients with lower FCP values (&amp;lt;250mg/g) spent 60 fewer minutes sitting (p=.25), and 52 more minutes standing (p=.12) during the day compared to patients with higher FCP values (&amp;gt;250mg/g). Patients with normal/mild disease severity (TMS &amp;lt;6) spent 83 fewer minutes per day sitting compared to those with moderate/severe disease severity (TMS &amp;gt;6, p=.12). CRP was not associated with any behavioural outcomes. Conclusion(s) In our study, daily steps appeared to be most strongly associated with FCP. While not statistically significant, patients with lower FCP reported less sitting and more standing compared to those with higher FCP. Future studies with larger sample sizes should continue to explore these activity behaviours and their potential associations with UC disease outcomes. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; Alberta's Collaboration of Excellence for Nutrition in Digestive Diseases (ASCEND) Disclosure of Interest B. Chiew: None Declared, K. Lyden Consultant of: PAL Technologies, the company that manufactures the activPAL device., A. Schick: None Declared, C. Ohland: None Declared, K. McCoy: None Declared, S. Kaur: None Declared, M. Yousuf: None Declared, L. Taylor: None Declared, M. Raman Shareholder of: LyfeMD – Director, Shareholder, Grant / Research support from: Pfizer, Takeda, Speakers bureau of: Fresenius Kabi, Pfizer, Mckesson, Takeda, Lupin, J. Vallance Grant / Research support from: Canada Research Chairs Program

СОДЕРЖАНИЕ КАЛЬПРОТЕКТИНА В СТУЛЕ И ЭОЗИНОФИЛЬНОГО ПРОТЕИНА Х В МОЧЕ У МЛАДЕНЦЕВ В ЗАВИСИМОСТИ ОТ ПОЛИМОРФИЗМА ГЕНОВ ИНТЕРЛЕЙКИНА-10 (G1082A, C592A) И ТОЛЛ-ПОДОБНОГО РЕЦЕПТОРА 4 (ASP299GLY)

Background. Cytokine and toll-like receptor gene polymorphisms may impact oral tolerance formation in infants. Objective: To determine the genotype distribution of IL-10 (G1082A, C592A) and TLR 4 (Asp299Gly) gene polymorphisms in children with different family history of allergy residing in Grodno region; to analyze the association between gene polymorphisms and concentrations of fecal calprotectin (FCP) and urine eosinophil protein X (UEoPX) in infants. Material and Methods. 92 infants were recruited and analyzed for IL-10 (G1082A, C592A) and TLR 4 (Asp299Gly) gene polymorphisms. Concentrations of FCP and UEoPX were examined in dynamics in children aged 1 and 3 months. Results. 80.4% and 48.9% of infants were carriers of the mutant allele of the G1082A and C592A polymorphisms respectively. 70.5% of children with negative family history of allergy were carriers of the wild G allele of G1082A polymorphism. Carriage of the mutant A allele of G1082A polymorphism is associated with lower FCP concentration in infants aged 1 month (AA: 1.9 ng/mL [1.9; 3.1], GA: 15.9 ng/mL [1.9; 93.8]) and GG: 88.3 ng/mL [2.4; 230.1]). The level of UEoPX in 3 months old infants with homozygote AA genotype was significantly (p=0.019) higher than in infants with heterozygote CA genotype (3.2 ng/ml [2.4; 4.5] and 2.3 ng/ml [1.3; 3.3] respectively). Conclusion. Carriage of the wild G allele of G1082A polymorphism is associated with higher fecal calprotectin concentration in one month old infants and significantly lower level of urine eosinophil protein X in 3 months old infants.

P333 Early intestinal ultrasound remission is associated with endoscopic healing after one year of infliximab therapy in Crohn’s disease: a multicentre prospective study

Abstract Background Endoscopic healing (EH) is currently the consensual long-term treatment target to achieve in Crohn’s disease (CD). However, optimization of therapy based on an endoscopic response implies a delay as endoscopy is an invasive procedure and cannot be used longitudinally, stressing the need for non-invasive predictors of EH. We aimed to assess the predictive role of biomarkers and intestinal ultrasound (IUS) parameters after induction therapy to predict EH one year after infliximab (IFX) therapy. Methods Prospective multicentre cohort study including patients with active CD starting IFX. Harvey-Bradshaw index (HBI), C-reactive protein (CRP), faecal calprotectin (FC), and IUS were performed at week (W) 0, 14, 30, and 54. Ileocolonoscopy was performed at W0 and W54. Clinical remission (CR) was defined as HBI&amp;lt;5 and laboratory remission (LR) as CRP &amp;lt;0.5mg/dL and FC &amp;lt;150ug/g. Transmural healing (TH) was defined as the normalization of bowel wall thickness (BWT≤3mm), doppler sign (≤1), wall stratification, and inflammatory fat in the most affected segment. The IBUS-SAS (International Bowel Ultrasound Segmental Activity Score) was used to assess disease activity and includes BWT, doppler sign, loss of stratification, and inflammatory fat. EH was defined as total SES-CD &amp;lt;3. Results We included 52 patients with CD (54% male; mean age 35±14y). Baseline characteristics are available in Table 1. At W14, 89% were in CR, 46% had LR and 19% had TH. After 1 year of IFX therapy, 90% were in CR, 62% had LR, 43% had TH and 37% had EH. At W14, patients with EH had lower BWT (3.3 vs 4.6mm, p=0.01), lower IBUS-SAS (15 vs 61, p&amp;lt;0.01), and lower FC (44 vs 239ug/g, p&amp;lt;0.01). At W14, both TH (OR 11.3, 95%CI 2.1-61.4, p&amp;lt;0.01) and FC remission (OR 7.4, 95%CI 1.8-30.7, p&amp;lt;0.01) were significant predictors for EH. In a multivariate analysis including significant baseline characteristics and early non-invasive monitoring targets at W14 (table 2), TH was an independent predictor of EH (OR 8.6, 95%CI 1.2-61.7, p=0.03). Even after adjusting for the baseline ultrasonographic severity according to the IBUS-SAS, TH at W14 remained a significant predictor of EH (OR 6.5, 95%CI 1.02-40.9, p=0.047). Using a ROC curves analysis, the IBUS-SAS at W14 was the best predictor for EH, with an AUC of 0.81 and the best cut-off value of 32.2 (Table 3). Conclusion Early assessment of ultrasonographic remission at week 14 can help predict EH after one year of therapy and offers an opportunity for early therapy optimization. TH at week 14 assessed by IUS was an independent predictor for EH after one year of therapy. Our results support the use of early IUS monitoring to predict response to therapy in CD patients.

P128 The role of small bowel capsule endoscopy as a diagnostic tool in isolated complex perianal disease

Abstract Background Isolated complicated perianal disease (cPD) might be the sole representation of Crohn’s disease (CD). We aimed to evaluate the impact of small bowel capsule endoscopy (SBCE) as a diagnostic tool for CD in this population. Methods A multicenter, retrospective cohort study from three tertiary centers. Patients with cPD who had a negative workup for CD (Ileocolonoscopy and cross-sectional imaging) and underwent evaluation with SBCE were included. Demographics, biomarkers, and the Lewis inflammatory score (LS) were recorded and analyzed. A LS≥135 was considered a positive SBCE. Results Ninety-one patients were included: 65 males (71.4%), mean age 40 (14) years, median duration of cPD 25.13 months (12.53-66.1). SBCE was positive in 24 patients (26.37%). Median LS was 675 (222-1518). Fecal calprotectin (FC) positively correlated with LS (r=0.81; p&amp;lt;0.0001): patients with a positive vs. negative SBCE had a significantly higher mean FC level (255 [389] vs 97[180], p=0.02), Figure 1. Correspondingly, a FC level ≥ 300 mg/kg had a specificity of 90% for a positive SBCE, while a cutoff of FC level &amp;lt;100 mg/kg or &amp;lt;50 mg/kg had a sensitivity of only 40% or 50% to rule out small bowel CD, respectively. Conclusion SBCE was positive in over a quarter of patients with cPD and a negative workup for CD. FC levels correlated with the degree of inflammation defined by the LS. However, the sensitivity of low FC to rule out CD was low. These results suggest that SBCE is an essential diagnostic tool for patients with cPD even after negative workup.

P430 Mesalazine dose modification based on fecal calprotectin levels in ulcerative colitis patients in clinical remission

Abstract Background Mesalazine is the most widely used maintenance therapy for ulcerative colitis (UC). The lowest effective dose recommended is 2g/day, although higher doses are often prescribed. Fecal calprotectin (FC) is a monitoring biomarker that correlates well with endoscopic remission and predicts clinical relapse. Our aim was to evaluate the suitability of mesalazine dose modification based on FC levels in asymptomatic UC patients. Methods Retrospective study in asymptomatic UC patients treated with oral mesalazine therapy which dose was modified in clinical practice according to FC levels between 2016-2022. Sustained clinical remission, clinical relapse and treatment escalation (increase in dose or introduction of rescue therapy) after dose change were assessed during follow-up. Results Mesalazine dose was reduced in 47 patients because of persistent low FC (mean 36ug/g; IQR 22-85); 51% extensive UC, median age of 55 years (IQR 43-63), median duration of clinical remission before dose-reduction 17 months (IQR 8-32) and mean baseline dose 3.2g/day (IQR 2-4). Mesalazine was reduced to 2g/day (IQR 0-2.4). A FC value &amp;gt;250 ug/g was observed at least once in 10% of subjects during follow-up. The cumulative probability of maintaining clinical remission after dose reduction was 90% and 82% at 12 and 24 months, respectively. Rescue therapy was used in 27%, 17% being corticosteroids. In 17 patients, mesalazine dose was increased due to high FC levels (mean 524ug/g; IQR 393-739); 47% extensive UC, median age 54 years (IQR 39-72), median duration of clinical remission before dose increase 16 months (IQR 11-33) and mean baseline dose 2.4g/day (IQR 1.5 -2.4). Dose was increased to 3.2g/day (IQR 3-4.4) and 58% presented FC &amp;lt;250 ug/g at least once during the follow-up. The cumulative probability of clinical recurrence after dose escalation was 14% and 28% at 12 and 24 months, respectively, and 29% needed rescue therapy (6% steroids). Conclusion Mesalazine dose modification based on CF levels in asymptomatic patients with UC appears to be a safe strategy and is followed by a low probability of clinical recurrence in the mid-term.

Serum oncostatin M predicts mucosal healing in patients with inflammatory bowel diseases treated with anti-TNF, but not vedolizumab.

Oncostatin M was recently highlighted as a promising biomarker for therapeutic effectiveness in inflammatory bowel diseases (IBD), with particular regard for infliximab. The primary aim was to evaluate the ability of serum oncostatin M to predict endoscopic response to different drugs in IBD. We selected two different cohorts of patients with IBD, treated with anti-TNF (infliximab and adalimumab) or with vedolizumab. Therapeutic response was evaluated at week 54 in terms of mucosal healing. Serum oncostatin M and C-reactive protein were measured at baseline; fecal calprotectin was measured at baseline and after 14 weeks of treatment. We evaluated the association of these biomarkers with mucosal healing at week 54. Among 66 patients treated with anti-TNFs and 68 treated with vedolizumab, 35 and 31 attained mucosal healing, respectively. Mucosal healing at 54 weeks was significantly associated with low oncostatin M levels at baseline in the anti-TNF cohort; the diagnostic accuracy of oncostatin M at baseline in predicting mucosal healing was 0.91 (95% CI 0.84 to 0.99) in the anti-TNF cohort and 0.56 (95% CI 0.43 to 0.70, P < 0.001) in the vedolizumab cohort. Mucosal healing was also associated with low fecal calprotectin levels at week 14 in both cohorts. Our study suggests that serum oncostatin M is a drug-specific biomarker, since it could be used to predict therapeutic effectiveness to anti-TNFs but not to vedolizumab. Moreover, these results emphasize the utility of serum oncostatin M measurement in patients treated with anti-TNF.