Normal Faecal Calprotectin Research Articles

Impact of ustekinumab exposure on clinical outcomes during induction in inflammatory bowel disease.

Understanding the relationship between ustekinumab (UST) exposure and clinical outcomes in inflammatory bowel disease (IBD) induction is crucial. However, evidence remains limited, highlighting the need to comprehend UST's pharmacokinetic variability for tailored treatments. This study aimed to investigate the association between UST exposure during the induction phase and clinical outcomes and identifying factors associated with UST exposure during this period. A retrospective observational study was conducted on a cohort of consecutive IBD patients. The primary endpoint was to assess the association between UST exposure at week 8 and both clinical and biochemical remission at week 26, as well as the absence of disease flare-ups during the initial six months of treatment. The secondary endpoint was to investigate the relationship between baseline characteristics and UST exposure at week 8. A total of 56 IBD patients were included. Variables associated with adequate UST exposure included baseline fecal calprotectin < 500 µg/g (OR: 7.72 [95% CI: 1.75-34.03]) and female sex (OR: 4.56 [95% CI: 1.12-18.60]). A cut-off UST trough leveles of 8.3 μg/mL yielded an area under the curve (AUC) of 0.74 (95% CI: 0.58-0.90, p=0.021) to predict normal fecal calprotectin levels, and 8.6 µg/ml resulted in an AUC of 0.724 (95% CI: 0.558-0.863) to predict clinical remission. This study demonstrates a significant association between UST concentrations and clinical and biochemical remission in IBD patients. Results suggest that standard induction doses may not be sufficient for all patients, highlighting the importance of treatment individualization to optimize outcomes.

Upadacitinib for Induction of Remission in Pediatric Ulcerative Colitis: An International Multi‑center Study.

Data on upadacitinib therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBD-U) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as an induction therapy in pediatric UC or IBD-U. In this multicenter retrospective study, children treated with upadacitinib for induction of remission of active UC or IBD-U from 30 centers worldwide were enrolled. Demographic, clinical and laboratory data as well as adverse events (AEs) were recorded at week 8 post induction. One hundred children were included (90 UC and 10 IBD-U, median age 15.6 [interquartile range 13.3-17.1] years). Ninety-eight were previously treated with biologic therapies, and 76 were treated with ≥2 biologics. At the end of the 8-week induction period, clinical response, clinical remission, and corticosteroid-free clinical remission (CFR) were observed in 84%, 62%, and 56% of the children, respectively. Normal C-reactive protein and fecal calprotectin (FC) <150 mcg/g were achieved in 75% and 50%, respectively. Combined CFR and FC remission was observed in 18/46 (39%) children with available data at 8 weeks. AEs were recorded in 37 children, including one serious AE of an appendiceal neuroendocrine tumor. The most frequent AEs were hyperlipidemia (n=13), acne (n=12), and infections (n=10, five of whom with herpes viruses). Upadacitinib is an effective induction therapy for refractory pediatric UC and IBD-U. Efficacy should be weighed against the potential risks of AEs.

Fecal Calprotectin as a Biomarker for Disease Activity in Microscopic Colitis

Background: Microscopic colitis (MC) is an intestinal inflammatory disorder. An objective biomarker to assess ongoing disease activity has not been previously examined. We aimed to examine the utility of fecal calprotectin (FC) measurement in symptomatic individuals with microscopic colitis. Methods: This cohort study included patients with a confirmed diagnosis of MC who had a calprotectin level measured in the setting of ongoing symptoms. We examined the frequency of elevation of FC in the setting of symptomatic microscopic colitis. Univariate and multivariate logistic regression models examined the independent predictors of elevated FC levels. Results: Our study included a total of 166 subjects, yielding 234 independent instances of FC measurement during symptomatic MC. Of all 234 FC measurements, 68 (29.0%) levels were &gt;150 mcg/g and 43 (18.4%) FC level&gt;250 mcg/g. Those with elevated FC levels&gt;150 mcg/g were older than those below this cutoff (54.7 vs. 61.5 y, P=0.011, respectively). A higher fraction of those with elevated FC (&gt; 150 mcg/g) had nocturnal bowel movements (41.2 vs. 24.1%, P=0.009) and fecal incontinence (25.0 vs. 13.3%, P=0.029) compared with those with normal FC levels. This association was further evidenced on multivariate analysis. There was no difference in FC levels between those who were responsive or refractory to steroids (138 mcg/g vs. 249 mcg/g, P=0.45). Conclusions: Elevated calprotectin concentrations were noted in over a quarter of patients with symptomatic microscopic colitis and were associated with more severe symptoms. However, FC levels did not indicate the likelihood of treatment response.

Real-World Effectiveness of Ustekinumab in Ulcerative Colitis in a United States Multicenter Cohort Consortium.

Pivotal trials have shown that ustekinumab is effective in ulcerative colitis (UC). However, the population included in these trials do not represent the cohort of patients treated in the real world. In this study, we aimed to describe the effectiveness and safety of ustekinumab in a clinical cohort of patients with UC. We performed a multicenter retrospective cohort study and included patients with active UC starting ustekinumab. Variables collected included demographics, clinical data, and disease activity (measured using partial Mayo score [PMS] and endoscopic Mayo score) at follow-up. The primary outcomes were cumulative rates of steroid-free clinical and biochemical remission (SFCBR), defined as a PMS <2 while off steroids and a normal C-reactive protein and/or fecal calprotectin. A total of 245 patients met inclusion criteria. The median time of follow-up was 33 (interquartile range, 17-53) weeks, and 214 (87.3%) had previous exposure to a biologic and/or tofacitinib. Rates of SFCBR, clinical remission, and endoscopic remission at 6 and 12 months were 12.0% (n = 16 of 139), 29.0% (n = 71 of 175), and 18.0% (n = 7 of 39), and 23.8% (n = 15 of 63), 54.3% (n = 57 of 105), and 31.0% (n = 9 of 29), respectively. Non-Hispanic White race, higher baseline PMS, and the use of concomitant corticosteroids were independently associated with failure to achieve SFCBR. Of the 73 that were dose escalated, 28.4% did not respond, 49.3% experienced a benefit, and 21.6% achieved remission. In a population enriched with refractory UC, ustekinumab was well tolerated and induced remission in a significant number of patients. Larger studies with a longer follow-up are warranted.

UPADACITINIB AS SECOND- AND THIRD-LINE SALVAGE THERAPY FOR REFRACTORY ACUTE SEVERE ULCERATIVE COLITIS

Abstract INTRODUCTION Intravenous (IV) corticosteroids (CS) remain first line therapy for acute severe ulcerative colitis (ASUC). Up to 40% are CS refractory. Prior biologic exposure, colonic drug loss and systemic toxicities limit their utility. Colectomy rates remain up to 30% in CS refractory cases emphasizing the need for expanding alternative strategies. We report our experience of upadacitinib (UPA) as 2nd and 3rd line salvage in refractory ASUC. METHODS ASUC was defined by Truelove and Witts’ criteria. Travis index was used to assess 3-day response to inpatient (IP) therapies. IP therapeutic non-response was defined as ≥ 8 bowel movements (BM)/day or &amp;gt; 2 BM and CRP &amp;gt; 45 mg/L. IP response was defined as ≤ 4 BM and CRP &amp;lt; 45 mg/L. Primary outcome include response to IP UPA salvage at day 3 and colectomy by week (WK) 16. Patients (pts) undergoing colectomy were followed until time to event. Secondary outcomes include post-discharge clinical and biochemical remission, clinical response and rate of adverse events at WK 8/16. Clinical remission/response was defined by STRIDE-2 guidelines using partial mayo (PM). Biochemical remission was defined as fecal calprotectin (FC) &amp;lt;250 ug/g or CRP &amp;lt;5 mg/L. No cardiovascular, thromboembolic or non-HSV infections were seen. RESULTS Four ASUC pts failing IV CS required inpatient UPA salvage (Table 1). At baseline, all pts had severe pancolonic endoscopic disease (median total mayo 11, median PM 9). Median exposure to prior advanced therapies was 4. Baseline median FC was 3000 ug/g and CRP 167 mg/dL. Pt #1, #2 received UPA as 2nd line salvage due to prior IFX failure (Table 2). Pts #3, #4 received UPA as 3rd line salvage due to IFX failure at index admission (IA). One received UPA 45 mg QD (pt #1) and three received 30 mg BID (pts #2-4). All pts achieved IP response to UPA. No pts needed colectomy at IA. Overall median length of hospital stay was 14 days. Median time to UPA response was 2.5 days. Discharge time post-UPA was 3.5 days. At WK 8, pt #1 attained response with resolution of rectal bleeding (RB), BM (-85%), CRP (-91%), FC (-82%), and PM 3 (Table 3-4). At WK 16, pt #1 met criteria for clinical and biochemical remission with PM 1, normal FC (-95%) and CRP (-98%). Pt #1,#3 achieved complete steroid taper and avoided colectomy over 16 WK. Pt #2 failed CS taper and had colectomy on day 33. Pt #3 achieved clinical and biochemical remission with PM 1 and CRP 5 mg/dL (-94%) at WK 8. At WK 16, pt #3 sustained CS free clinical and biochemical remission with normalized BM (-93%), FC (-92%), CRP (-98%) and sustained resolution of RB. Assessment of pt #4 was limited to IP UPA response pending follow up. Outcomes were similar in pts receiving UPA as 2nd and 3rd line salvage. CONCLUSION We report efficacy and safety of UPA as 2nd and 3rd line salvage for ASUC thus expanding the armamentarium for medical salvage therapy. Table 1 Baseline Disease Characteristics Table 2 Patient Specific Inpatient Therapy Table 3 Comparison of Disease Activity Parameters at Baseline, Discharge, 8 Weeks and 16 Weeks Table 4 Percentage Difference of Disease Activity Parameters at Discharge, 8 Weeks and 16 Weeks in Comparison to Baseline

P244 The first step to IBD prevention exploring rate of pre-clinical inflammation in subset of asymptomatic subjects at risk of IBD: screening stage of the PIONIR trial

Abstract Background With the increasing prevalence of inflammatory bowel diseases (IBD) globally, it is necessary to start focusing efforts on prevention of the diseases. The Genetic, Environmental, Microbial (GEM) study identified biological signatures predictive of developing IBD in first degree relatives (FDR) of patients with Crohn’s disease (CD). The ongoing PIONIR (Preventing IBD ONset in Individuals at Risk) study is a randomized controlled trial aimed to explore whether the Tasty &amp; Healthy diet can change the CD-risk associated biomarkers of healthy FDRs who are particularly high risk of developing CD, originally followed in the GEM cohort. We report here the rate of IBD and pre-IBD inflammation in a subset cohort. Methods Subjects, 6-35 years of age from the GEM cohort who were identified by a combination of predictors at recruitment to GEM to have an increased risk for persistently elevated fecal calprotectin (FC) (i.e. Microbiome Risk Score (MRS), increased gut permeability and/or multiplex family of CD) were approached to perform a new FC test. Subjects who had FC&amp;gt;70µg/g, confirmed by a second sample, were offered a panenteric video capsule endoscopy (VCE), but some elected to proceed to ileocolonoscopy instead. Results For the PIONIR recruitment, a total of 450 subjects were approached from 7 sites in Israel and Canada, of whom 183 consented and provided a stool sample for FC (Figure). FC was elevated in 57 (31%) subjects, confirmed by re-testing in 36 (20%); 25/36 underwent VCE/ileocolonoscopy (Figure). In total, 8 (4.4% of the screened cohort) had normal-appearing mucosa, in 10 (5.5%) there were non-specific mucosal changes (e.g. several erosions or erythema), 6 (3.3%) had ulcers compatible with CD and 1 (0.6%) was inconclusive. The median FC of those eventually diagnosed with CD (816 [IQR 361-1123) was higher than the remaining 30 without IBD with elevated FC (175 [111-281], p=0.003). FC&amp;gt;275µg/g was highly predictive of CD in the entire cohort (AUROC 0.97 (95%CI 0.93-0.99); sensitivity 83%, specificity 94%). Conclusion Preclinical mucosal inflammation in VCE/ileocolonoscopy was found in 18 of 183 (9.8%) screened subjects (i.e. elevated FC with either normal or nonspecific mucosal findings), 134 (73%) had normal FC and 11 (6%) with elevated FC had missing VCE/ileocolonoscopy data. Six had CD (3.3%, or 17% of the 36 with elevated FC). Detecting subjects at risk at their preclinical stages, possibly with FC&amp;gt;275µg/g, is the first necessary step in developing preventive strategies for IBD.

P199 External validation of Intestinal Ultrasound score: IBUS-SAS with clinical (CDAI), biomarkers and endoscopic scoring system (SES-CD)

Abstract Background Intestinal ultrasound (IUS) is a non-invasive tool for assessing disease activity in patients with Inflammatory bowel disease. International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) is a comprehensive score proposed by an expert consensus with good reliability. We aim to assess the correlation of the IBUS-SAS with clinical and endoscopic scores and biomarkers in patients with Crohn’s disease (CD) in a point-of-care setting. Methods This retrospective study was conducted from October 2021 to September 2023. All patients with CD who underwent colonoscopy at initial presentation or assessing disease activity on follow-up were included. At the clinic visit, Crohn’s disease activity index (CDAI), C-reactive protein levels (CRP), Faecal calprotectin (FC) were documented. IUS was performed in the clinic and IBUS-SAS was documented. A colonoscopy was done within 1 week of the clinic visit. Endoscopic disease activity was documented using Simple Endoscopic Score in Crohn’s disease (SES-CD). Statistical Analysis Pearson’s correlation was performed between IBUS-SAS and the clinical and endoscopic scores and the biomarkers. ROC analysis was done to assess the threshold value of IBUS-SAS to predict the presence of endoscopic disease activity. Results 181 patients were included in the study. In patients with clinical remission, the median IBUS-SAS was 8 (± 23.5). The median IBUS-SAS was 62 (± 21.47), 70 (± 15.47) &amp; 64 (± 0.58) in patients with mild, moderate to severe &amp; severe CDAI respectively. The Pearson correlation coefficient between IBUS-SAS &amp; CDAI was 0.7 (95% CI 0.62-0.77; p &amp;lt; 0.001). The IBUS-SAS in patients with normal CRP levels (&amp;lt; 5mg/L) was 8 (± 19.54) &amp; in patients with elevated CRP was 64 (± 18.99). The IBUS-SAS in patients with normal FC was 8 (± 19.65) &amp; elevated FC (&amp;gt;250mcg/g) was 64.5 (± 22.66). The Pearson correlation coefficient between IBUS-SAS &amp; CRP was 0.49(95% CI 0.37-0.60; p &amp;lt; 0.001) and with FC was 0.58 (95% CI 0.46-0.68; p &amp;lt; 0.001). The IBUS-SAS correlated well with SES-CD score with IBUS SAS scores of 8 (± 12.92), 53.5 (± 16.35), 65 (± 20.83) &amp; 65 (± 8.62) in patients with inactive, mild, moderate, &amp; severe SES-CD respectively. The Pearson correlation coefficient between IBUS-SAS &amp; SES-CD was 0.77 (95% CI 0.7-0.82; p &amp;lt; 0.001). The IBUS-SAS score of &amp;gt; 37.5 revealed an area under the curve of 0.96 (95% CI 0.92 – 0.99) with a sensitivity of 94% &amp; specificity of 91% to predict endoscopic disease activity (SES-CD &amp;gt; 3). Conclusion The IBUS-SAS score correlated very well with clinical and endoscopic disease activity as well as biomarkers. A score &amp;gt; 37.5 had a sensitivity of 94% and specificity of 91% to predict the presence of endoscopic disease activity.

P208 Personalized Machine Learning Algorithm to Predict Ulcerative Colitis Disease Activity from Wearable Data

Abstract Background Due to its ease of use and ability to determine complex information, wearables have been gaining popularity over the last decade. Smart rings such as OuraTM present the ability to track metrics such as sleep quality, resting heart rate, body temperature, and daily activity. This is not only useful for the predicting disease activity in inflammatory bowel disease (IBD), but also to understand behavior changes that can be associated with disease activity. This study aimed to evaluate potential use for wearable data in IBD management. Methods Daily OuraTM ring data of a patient with ulcerative colitis (UC) was collected from OuraTM ring application programming interface from 2019 to 2023. Days were classified as “active disease” or “remission” based on patient symptoms, colonoscopies, and fecal calprotectin levels. Data was collected on the patient’s sleep metrics, activity levels, and daily vitals. Variables with &amp;gt;50% null values were not included in model training. A univariate analysis was conducted to determine features that correlated with flaring periods (p-value &amp;lt;0.3) [ABPM1] [AS2] to be included in model training. An XGBoost classifier was selected with the target variable being flare status. Boosting parameters were then hypertuned to optimize model performance. After hypertuning and kfold cross-validation, the model’s mean accuracy, mean logarithmic loss, and AUC was reported. Further analysis was conducted comparing remission, active disease and pre-diagnosis data. Results 963 days were collected. 444 days were determined to be “flare” based on reported symptoms, 4 fecal calprotectin levels, 2 colonoscopies, and 1 intestinal ultrasound confirming disease activity. Remission was determined by no reported symptoms, 2 normal fecal calprotectin levels and a normal intestinal ultrasound. Generally, worse sleep quality, increased resting heart rate, increased respiratory rate, and deviations in activity levels were positively associated with disease activity. After model training with XGBoost classifier and 10-fold stratified cross-validation, the mean accuracy was 0.92 ± 0.08, mean logarithmic loss of 0.134 ± 0.11, and a mean AUC was 0.94 ± 0.02. The patient’s mean biometric values such as heart rate and respiratory appeared to recover to pre-diagnosis levels with the exception of heart rate. Conclusion Data from the OuraTM ring demonstrated the potential application of wearables in IBD management in a single patient with UC. The high accuracy and AUC of our XGBoost model demonstrates how individualized wearable data can be used to predict IBD flares. Prospective studies with multiple patients could be useful to consider wearables as an additional adjunct disease monitoring device in IBD.

Factors contributing to flares of ulcerative colitis in North India- a case-control study

BackgroundUlcerative colitis is a relapsing and remitting disease that may be associated with flares. The causes of flares in the Indian setting are not well recognized.MethodsThe present prospective case-control study was conducted at a single center in North India. Cases were defined as patients admitted for flare of ulcerative colitis, while controls were patients in remission enrolled from the outpatient department. The basis of the diagnosis of flare was a simple clinical colitis activity index (SCCAI) of ≥ 5 and endoscopic activity, while remission was based on SCCAI < 4 and a normal fecal calprotectin. A questionnaire evaluating recent infections, stress, drug intake (antibiotics, pain medication), adherence to therapy, and use of complementary and alternative therapy (CAM) was administered.ResultsWe included 84 patients (51 with flare and 33 in remission) with a median age of 38 years, of whom 47 (55.9%) were males. The two groups were similar for baseline parameters, including age (38, 23–50 and 38, 25.5–48.5 years), male gender (52.9% and 60.6%), extent of disease, extraintestinal manifestations (21.6% and 12.1%), use of 5-aminosalicylates (76.5% and 90.9%). The thiopurine use was lower in those having a flare (15.7% and 36.4%). Amongst the predictors of flare, the recent infections (39.2% and 30.3%), recent travel (31.4 and 27.3%), eating outside food (47.1% and 39.4%), consumption of milk products (88.2% and 75.8%), use of pain medication (43.1% and 33.3%) and recent stress (62.7% and 60.6%) were similar between cases and controls. The rates of antibiotic use (29.4% and 6.1%), lack of adherence (50.9% and 15.2%), and intake of CAM (70.6% and 33.3%) were higher in those with flare. Patients attributed a lack of adherence to the cost of therapy, presumed cure (due to lack of symptoms), and fear of adverse effects.ConclusionLack of adherence to inflammatory bowel disease therapies and recent CAM and antibiotic intake was higher in patients with flares of UC. The study makes ground for educational intervention(s) promoting knowledge and adherence to IBD therapies.

Higher Intra-Abdominal Visceral Adipose Tissue Mass Is Associated With Lower Rates of Clinical and Endoscopic Remission in Patients With Inflammatory Bowel Diseases Initiating Biologic Therapy: Results of the Constellation Study

We sought to assess the association between intra-abdominal visceral adipose tissue (IA-VAT) and response to 3 different biologic drugs in patients with inflammatory bowel disease (IBD) and to investigate its effects on inflammatory cytokine expression, pharmacokinetics, and intestinal microbiota. We prospectively enrolled subjects with active IBD initiating infliximab, vedolizumab, or ustekinumab and a healthy control group. Baseline body composition (including IA-VAT as percent of total body mass [IA-VAT%]) was measured using GE iDXA scan. Primary outcome was corticosteroid- free deep remission at weeks 14-16, defined as Harvey Bradshaw Index <5 for Crohn's disease and partial Mayo score <2 for ulcerative colitis, with a normal C-reactive protein and fecal calprotectin. Secondary outcomes were corticosteroid-free deep remission and endoscopic remission (Endoscopic Mayo Score ≤1 in ulcerative colitis or Simple Endoscopic Score for Crohn's disease ≤2) at weeks 30-46. A total of 141 patients with IBD and 51 healthy controls were included. No differences in body composition parameters were seen between the IBD and healthy control cohorts. Patients with higher IA-VAT% were less likely to achieve corticosteroid-free deep remission (P < .001) or endoscopic remission (P= .02) vs those with lower IA-VAT%. Furthermore, nonresponders with high IA-VAT% had significantly higher serum interleukin-6 and tumor necrosis factor at baseline compared with responders and patients with low IA-VAT%. Drug pharmacokinetic properties and microbiota diversity were similar when comparing high and low IA-VAT% groups. Higher IA-VAT% was independently associated with worse outcomes. This association could be driven at least partially by discrete differences in inflammatory cytokine expression.

P153 Association between ustekinumab trough concentrations and clinical, biochemical, and endoscopic outcomes in patients with Inflammatory Bowel Disease

Abstract Background Ustekinumab (UST), an inhibitor of the p40 subunit of interleukins 12 and 23, is an effective treatment for patients with Crohn’s disease (CD) and ulcerative colitis (UC). There is limited data on therapeutic outcomes and UST trough levels (UTL). We aimed to evaluate the association between UTL and corticosteroid-free clinical remission. We also assessed the relationship between UTL and endoscopic remission as a secondary outcome. Methods We performed a cross-sectional study on IBD patients receiving maintenance therapy with UST (&amp;gt;6 months). We included UTL, C reactive protein (CRP), faecal calprotectin (FC), and clinical and endoscopic indexes (Harvey Bradshaw [HBI] and simple endoscopic score [SES-CD] for CD patients; and partial Mayo score [PMS] and endoscopic Mayo score [EMS] for UC patients). Corticosteroid-free clinical remission (CSF-CR) was defined as HBI&amp;lt;5 or PMS&amp;lt;2 plus normal CRP and/or FC values without corticosteroids. Endoscopic remission was defined as SES-CD&amp;lt;3 or EMS&amp;lt;2. Results We included 105 patients; the mean age was 50 years, and 59% were female (Figure 1). Eighty-seven patients had CD, and 92% had previously received an anti-TNF. The median time on UST was 121 weeks at inclusion. Sixty-four patients received 90mg subcutaneous (SC) every 4 weeks, 40 patients 90mg SC every 8 weeks, and 1 patient 90mg SC every 12 weeks. Eighty percent were in CSF-CR, and 53% were in endoscopic remission. Median UTL were 2,7µg/mL (IQR: 1,7-4,1µg/mL); UST antibodies were not detected. Patients in CSF-CR and endoscopic remission did not show significantly higher UTL (3,4µg/mL vs. 2,5µg/mL, p=0,147; and 3,6µg/mL vs. 3,7µg/mL, p=0,903, respectively). No differences in UTL were detected between patients on monotherapy and combination therapy (2,9µg/mL vs. 3,3µg/mL, p=0,456). Conclusion No association between UTL and clinical or endoscopic activity was observed in our predominantly biologic-experienced cohort. Further prospective studies are needed to determine the role of therapeutic drug monitoring while on UST.

P36 Crohn’s-associated inflammatory arthritis treated successfully with upadacitinib

Introduction/BackgroundEnteropathic arthritis is inflammatory arthritis which is associated with inflammatory bowel disease such as Crohn’s disease and ulcerative colitis. The optimal treatment for patients is one which is effective for both arthritis and bowel disease. First line treatments include DMARDs such as methotrexate and sulfasalazine. Second line options include anti-TNF biologics such as infliximab and adalimumab, and the anti-IL-12/23 biologic ustekinumab. There is currently little guidance on choice of treatment if these options fail. We present a case of Crohn’s-associated inflammatory arthritis which did not respond to two anti-TNFs but was successfully treated with the JAK inhibitor upadacinitib.Description/MethodA 30-year-old male was referred to gastroenterology with a 4 month history of diarrhoea and weight loss. His faecal calprotectin was raised at 982µg/g. He had a history of seronegative inflammatory arthritis diagnosed 5 years previously. He had been treated initially with methotrexate and sulfasalazine, which were discontinued due to side effects and inefficacy, and his arthritis was subsequently well-controlled on etanercept for the last year.Colonoscopy showed patchy colitis at the rectum which was continuous in the transverse and ascending colon and caecum. The appearances and mucosal biopsy were consistent with moderately active Crohn’s colitis. In view of this, etanercept was switched to adalimumab, which was administered using the accelerated loading regimen used in IBD.Five weeks after switching the patient developed a flare of arthritis with knee and ankle inflammation and CRP 30. He was given oral steroids and reviewed in a combined rheumatology/gastroenterology clinic. The frequency of adalimumab was increased to 40mg weekly and subcutaneous methotrexate 10mg weekly was introduced.Despite this, the patient’s arthritis remained active, although with some improvement in his bowel symptoms and a fall in faecal calprotectin to 117µg/g. Adalimumab was switched to certolizumab and methotrexate increased to 15mg weekly with intra-muscular steroids. On certolizumab he developed progressively more active arthritis with CRP 83, bilateral ankle inflammation and large knee effusions requiring aspiration and steroid injection.After 8 weeks of certolizumab, there was no improvement and the decision was made to switch to upadacitinib 15mg daily. Within 4 weeks of treatment with upadacitinib he noticed a significant improvement in his arthritis and after 12 weeks was in clinical remission with normal CRP and faecal calprotectin. Methotrexate was later discontinued due to nausea. Over 12 months later the patient remains in remission for both bowel disease and arthritis on upadacitinib monotherapy.Discussion/ResultsIn enteropathic arthritis, joint symptoms may precede or follow bowel disease. Etanercept, a recombinant TNF-receptor fusion protein, is not an effective treatment for IBD. Indeed, there are case reports and observational data to suggest that etanercept may be associated with an increased risk of developing IBD in some patients. In our case the patient developed Crohn’s disease while taking etanercept and the switch to adalimumab precipitated a flare of his arthritis which was not controlled by treatment intensification. The failure of two anti-TNF biologics, adalimumab and certolizumab, may point to the activation of alternative cytokine inflammatory pathways as the driver of the patient’s disease.Our patient was managed in a combined rheumatology/gastroenterology clinic which enabled an inter-specialty approach to managing both aspects of his disease. After the failure of certolizumub we made the decision to trial upadacitinib, a selective JAK1 inhibitor, owing to our experience of its effectiveness in rheumatoid and psoriatic arthritis, and its promising results in Phase 3 trials in Crohn’s disease. We considered ustekinumab but opted against it as in our experience it may be suboptimal in patients in whom arthritis is the most troublesome symptom. Upadacitinib worked quickly and effectively to control our patient’s arthritis alongside his bowel disease and was well tolerated.There are currently limited treatments which are effective for both IBD and arthritis, and there is little guidance on treatment strategies in enteropathic arthritis if anti-TNF and ustekinumab are unsuccessful. Tofacitinib, a JAK1/3 inhibitor, is licensed for rheumatoid and psoriatic arthritis and ulcerative colitis, but is not effective for Crohn’s disease. Upadacitinib is undergoing Phase 3 trials in Crohn’s disease and our case highlights its potential role in the treatment of patients with Crohn’s disease and inflammatory arthritis in whom anti-TNF therapy is unsuccessful.Key learning points/Conclusion1. Etanercept is not an effective treatment for inflammatory bowel disease and may necessitate a change to another anti-TNF biologic such as infliximab or adalimumab.2. Upadacitinib, a selective JAK1 inhibitor, was successfully used in our case to treat both arthritis and bowel disease. Although this was just one case, the results of Phase 3 trials suggest a promising role for upadacitinib in Crohn’s disease and it is already used in the treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.3. Patients with enteropathic arthritis may be best managed in a specialist combined gastroenterology and rheumatology clinic where a holistic approach to the management of both aspects of their disease can be undertaken.

P383 Ustekinumab as an opportunity for refractory Ulcerative Colitis patients

Abstract Background There are limited data in real-life of ustekinumab (USK) used in ulcerative colitis (UC). The aim of this study was to assess the effectiveness and safety in clinical practice of USK in UC in the medium and long-term. Methods Observational study in UC patients who received USK at the recommended dose based on weight ~6 mg/kg IV week, 0.90 mg SC week, 8 and maintenance, 90 mg SC every, 8 or, 12 weeks and with, 1 year of follow-up. The partial Mayo score (PMS) was used to assess clinical remission (PMS≤, 2). The PMS, C-reactive protein (CRP) and faecal calprotectin (FC) values ​​were recorded at baseline and after, 8, 16, 24 and, 52 weeks. Dose adjustment was performed by the measure of UST trough levels by ELISA, when patient lost clinical and/or biochemical response and the levels were low (&amp;lt;1.3 µg/ml). Demographic, clinical, biochemical and endoscopic data, previous treatments, adverse events (AEs), surgeries and hospitalizations, were documented. Results Twenty-three patients with UC were analysed. (Table, 1). All patients had received previous biological treatment:, 52% ≥2 anti-TNF, 65% vedolizumab and, 30% JAK inhibitors. Treatment discontinuation occurred in, 3 patients (13%). The persistence was, 83% and, 79% at, 6 and, 12 months (Figure, 1). During follow-up, 12 patients (52%) maintained standard dose of USK. Dose adjustment was performed in, 13 patients (56%):, 3 (13%) required intravenous UST reinduction and, 10 (43%) required dose escalation (8 by shortening the interval between doses and, 2 by switching to intravenous USK administration). Clinical remission was reached in, 61%, 58%, 56%, 79% of the patients after, 8, 16, 24, 52 weeks, respectively. Normal CRP (&amp;lt;5mg/L) and FC (&amp;lt;150 µg/g) levels were achieved in, 76%, 93% and, 80% and in, 35%, 31% and, 40% of patients after, 8, 24, 52 weeks, respectively. Five of, 6 patients who had endoscopy before and after treatment showed endoscopic Mayo subscore ≤1. There were, 2 AEs, 1 hospitalization, and, 1 colectomy during follow-up. Conclusion This study demonstrates the safety as well as the clinical, biological and endoscopic effectiveness of USK adjusted by levels in real life in a highly refractory UC cohort.

Commonly used biomarkers do not contribute to diagnosing irritable bowel syndrome.

The aim of this article was to examine the costs and effectiveness of standardized blood and fecal investigations in patients fulfilling the Rome criteria for irritable bowel syndrome (IBS). We conducted a real-life cohort study in patients fulfilling the Rome III criteria for IBS without red flag signs or symptoms, in a center of excellence for IBS patients from 1 January 2015 till 1 January 2019. Standardized blood and fecal investigations [hemoglobin (Hb), thyroid-stimulating hormone (TSH), coeliac serology, and fecal calprotectin (FCP)] were performed during the first consultation. Patients were followed for at least 1 year. Primary outcome was the probability of another diagnosis than IBS with subsequent overall costs. A total of 218 patients were included. In approximately 200 patients blood and fecal investigations were performed and 47 patients underwent a colonoscopy. Two-hundred ten patients were diagnosed with IBS, 5 with inflammatory bowel disease (IBD), 1 with nonspecific acute ileitis, 1 with hyperthyroidism, and 1 with coeliac disease. The number needed to diagnose all included laboratory tests was 34, and for the individual test: TSH 197, coeliac serology 199, and FCP 50. The total costs were approximately €4900 to diagnose one patient with another diagnosis than IBS. In our real-life cohort of adult patients under the age of 50 years fulfilling the Rome criteria for IBS without red flag symptoms, standardized blood, and fecal investigations have a very low diagnostic yield accompanied by high additional costs. Colonoscopy is not indicated in patients with Rome III positive IBS and normal FCP.

S2977 Eosinophilic Ascites: Rare Presentations of Eosinophilic Gastroenteritis (EGE)

Introduction: Eosinophilic gastroenteritis (EGE) is a rare disorder characterized by eosinophilic infiltration of the gastrointestinal tract in the absence of other causes of intestinal eosinophilia. We describe a case of EGE presenting with eosinophilic ascites. Case Description/Methods: A 33-year-old male with schizophrenia and suspected familial adenomatous polyposis (FAP) was admitted with 2 days of nausea, vomiting, and diarrhea associated with 10 lbs. weight loss over the past 2 weeks. The exam was notable for abdominal distension with shifting dullness and diffused tenderness. Initial labs showed normal electrolytes and liver chemistries, WBC 13.8x103/µL (4.3-10x103/µL) with eosinophil predominance (60%, 8.29X103/µL (0.04-0.54X103/µL), CRP 17.43mg/L (0-3mg/L), and creatinine 1.5mg/dL (0.7-1.3mg/dL). Stool studies were negative for bacterial, ova, and parasitic infections. Further blood work showed normal IgE, fecal calprotectin, and Strongyloides IgG. Flow cytometry did not reveal any myelolymphoproliferative findings. Abdominal ultrasound showed hepatosplenomegaly with large ascites. He underwent paracentesis revealed WBC 12,154 with 97% eosinophil count and negative gram stain and AFB culture. He underwent push enteroscopy which showed esophagitis, duodenitis, and normal jejunum, and flexible sigmoidoscopy which showed distal colonic edema with patchy erythematous mucosa (Figure 1). Random biopsies were obtained from different parts of the gastrointestinal tract revealed increased eosinophils (up to 50 eosinophils/HPF) in the duodenum consistent with eosinophilic gastroenteritis (EGE) (Figure 2). The patient was started on 14 days of prednisone 40mg daily with taper. The patient was seen in the clinic 2 weeks later with normal eosinophil count and resolution of symptoms. Discussion: Clinical presentations of EGE are related to the layers and the extent of the bowel involved. While eosinophilic infiltration on an endoscopic biopsy suggests predominantly mucosal disease, patient with subserosal involvement typically presents with eosinophilic ascites. Our patient has evidence of both mucosal and subserosal involvement which eventually responds to steroid therapy. EGE should be suspected in patients presenting with gastrointestinal symptoms associated with eosinophilic ascites and peripheral eosinophilia. Endoscopic evaluation should be pursued to confirm the diagnosis.Figure 1.: Endoscopic finding A) esophagitis, B) duodenitis, C & D) distal colonic edema with patchy erythematous mucosa

Serum Levels of PCSK9 Are Increased in Patients With Active Ulcerative Colitis Representing a Potential Biomarker of Disease Activity: A Cross-sectional Study.

Ulcerative colitis (UC) is characterized by chronic inflammation and progressive course, with potential extraintestinal complications including cardiovascular mortality. Serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels have been recently recognized as biomarkers of low-grade inflammation and cardiovascular disease. The aim of our study was to evaluate PCSK9 levels in patients with UC and different degrees of disease activity. We prospectively recruited consecutive patients with UC attending our center at the University Hospital of Padua. Demographics, clinical characteristics, and biochemical data, including PCSK9, high sensitivity C-reactive protein, and fecal calprotectin, were recorded. Moreover, endoscopic procedures were performed in all subjects. We included 112 patients with UC (mean age=52.62±12.84 y; 52.62% males). Patients with UC and abnormal fecal calprotectin (≥250 µg/g) and/or C-reactive protein (≥3 mg/L) had greater levels of PCSK9 compared with UC patients with normal fecal calprotectin and high sensitivity C-reactive protein ( P =0.03 and 0.005, respectively). Higher endoscopic scores in UC were characterized by greater levels of PCSK9 ( P =0.03). Furthermore, we found a positive correlation between PCSK9 levels and fecal calprotectin ( r =0.18, P =0.04), endoscopic Mayo Score ( r =0.25, P =0.007), and UC-Riley Index ( r =0.22, P =0.01). We also found a positive correlation between PCSK9 levels and both total and low-density lipoprotein cholesterol values ( P <0.05). Serum PCSK9 levels are increased in patients with biochemical and endoscopic evidence of active disease in UC. Further longitudinal studies are necessary to evaluate the role of PCSK9 as a potential biomarker of disease activity and cardiovascular risk in UC.

P343 Maintenance of deep remission in Crohn’s disease after switching from anti–TNF to ustekinumab

Abstract Background Anti-TNF agents, infliximab (IFX) and adalimumab (ADL) are first line treatment for moderate-to-severe Crohn’s disease (CD) and for preventing post-operative recurrence of CD (CD-POR) following right hemicolectomy (RH). However, a considerable proportion of patients develop allergic reactions and/or paradoxical inflammation to anti-TNFs necessitating switching to out of class biologic despite deep remission. We aimed to assess whether ustekinumab (UST), an IL12/IL23 inhibitor, can maintain deep remission in these patients. Methods This prospective, single centre study enrolled CD patients with B1 phenotype or on POR preventive therapy who were in prolonged deep remission when became intolerable of anti-TNFs. Deep remission was defined as clinical (HBI&amp;lt;4), biomarker (normal CRP and faecal calprotectin [FC&amp;lt;150μg/dl]), and endoscopic remission (SES-CD≤2 or Rutgeerts’ score [RS]≤1). Patients received UST (6mg/kg iv followed by 90mg sc q8 weeks) and were followed every 2 months with HBI score calculation and routine laboratory tests. Ileocolonoscopy was performed at 1y after UST initiation and the SES-CD or the RS were calculated. Absence of deep remission was defined as clinical (HBI&amp;gt;5), or biomarker relapse or endoscopic recurrence (SES-CD&amp;gt;2 or RS≥2, respectively). Results Twenty five patients (15 males), median age(range) 42(20-65)y were included. Seven patients had undergone RH, 6 had colitis and 12 had ileitis or ileocolitis; 13 patients had received ADL, 8 IFX and 4 both. Patients were in deep remission for 3.8 (2-10)y [median (range)]. Reasons for switching were severe psoriasis/proriasiform lesions (11), persistent arthralgias (10), infusion/injection reactions (2), anti-TNF-induced lupus erythematosus (2), sweet syndrome (1), and vasculitis (1). Two patients had more than one paradoxical inflammation. At baseline the median (range) CRP was 0.21mg/dl (0.10-0.40), FC 52μg/g (20-114). Trough levels for anti-TNFs in 15/25 patients were normal without antibodies. At 1-year post-switching endoscopic CD-POR was seen in 3/7 patients (RS≥2b) associated with biomarker relapse in 2 and clinical relapse in 1 patient. Of 18 patients with B1 phenotype deep remission was maintained in 15: two patients with infusion reactions to IFX relapsed and 1 patient developed endoscopic lesions in view of normal CRP but abnormal FC (SES-CD 6, 5 and 3, respectively). Paradoxical inflammation resolved in all 23 patients but de novo arthralgias developed in 2 patients. Thus, one year after switching to UST, 19/25 CD patients maintained deep remission. Conclusion UST seems to be a reliable therapeutic alternative for anti-TNF-dependent patients who have who cannot tolerate anti-TNFs.

P152 Bowel ultrasound as an early monitoring tool to assess disease activity in Crohn’s disease patients after induction therapy with infliximab

Abstract Background Bowel wall thickness (BWT) is an accurate sonographic parameter to assess disease activity in Crohn’s disease (CD). International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) was developed to allow a reproducible assessment of intestinal inflammation in CD using bowel ultrasound (IUS). Aim to assess BWT and IBUS-SAS variation after induction therapy with infliximab (IFX) and their correlation with clinical and laboratory parameters. Methods Prospective multicentre 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 0 (W0) and 14 (W14). IUS response and remission were defined as a reduction in BWT ≥25% and its normalization(≤3mm) in the most affected segment, respectively. IBUS-SAS was calculated using BWT, Doppler signal, bowel wall stratification (BWS) and inflammatory fat. Results We included 37 patients (62% males; median age 30 years, range 16–73). According to Montreal classification, most patients were A2 (70%), had ileocolonic disease (L3 57%) and an inflammatory phenotype (B1 60%); 41% had perianal disease. Most were anti-TNF therapy naive(84%), and combination therapy was used in 62%. Terminal ileum was the most affected segment identified by IUS (60%). Table 1 shows clinical, laboratory and sonographic parameters [median (IQR)]. At W14, 81% were in clinical remission, 43% in laboratorial remission (normal CRP and FC), 24% had IUS response and 11% had IUS remission. There was a significant reduction in HBI, CRP, FC and sonographic parameters (except for BWS) between W0 and W14. We found a fair to good correlation between BWT and HBI(r=0.363, p=0.03), CRP(r=0.391, p=0.02) and FC(r=0.373, p=0.03) at W14. IBUS-SAS had also a fair to good correlation with CRP(r=0.340, p=0.04) and FC(r=0.527, p=0.001) at W14. The area under the curve of IBUS-SAS for predicting clinical and laboratorial remission was 0.60; best-cut off 64.65 (sens. 57%; specif. 63%). Conclusion There was a significant reduction in sonographic parameters after 14 weeks of IFX and one quarter of our patients had an IUS response, suggesting that reduction in BWT could be an early marker of response to therapy. We found a good correlation between IUS and clinical and laboratory parameters at W14. IUS evaluation after induction therapy can be a helpful tool to monitor disease activity and guide CD patient management in our daily practice.

P505 Early therapeutic drug monitoring after induction therapy with infliximab: correlation with intestinal ultrasound

Abstract Background Therapeutic drug monitoring (TDM) in patients receiving infliximab (IFX) has a role in assessing treatment and managing outcomes. Infliximab trough levels (ITL) have been suggested as useful markers for treatment optimization in Crohn’s disease (CD).Our goals were: to assess the relationship between ITL and transmural inflammation as assessed by intestinal ultrasound(IUS), following induction therapy with IFX; to assess which clinical, laboratorial or IUS parameters better predicted adequate levels by the end of induction therapy. Methods Prospective multicentric cohort study including patients with active CD starting IFX therapy. Clinical disease activity assessed using the Harvey-Bradshaw index (HBI), C-reactive protein (CRP), fecal calprotectin (FC) were measured at week 0 and after induction therapy (week 14). IUS was performed at week 0 and 14, bowel wall thickness (BWT) from the worst segment was selected for analysis. Ileocolonoscopy was performed at W0 and SES-CD was registered. ITL were measured at W14. Results We included 36 patients with CD (61% male; median age 30 years (range 16–73)). According to Montreal classification, most patients were A2 (69%), had ileocolonic disease (L3 56%) and an inflammatory phenotype (B1 58%).Perianal disease was present in 42%. Combination therapy was used in 61%. After induction therapy, 81% were in clinical remission (HBI &amp;lt;5) and 43% had laboratorial remission (normal CRP and FC). IUS response (decrease &amp;gt;25% in BWT) was observed in 24% of patients and remission (BWT normalization) in 11%. Median ITL were 4.3 (IQR 2.3–8.1) and 64% had ITL &amp;gt;3 ug/ml. There was a good negative correlation between ITL and SES-CD (r=-0.492, p=0.003). Adequate ITL were associated with lower HBI (1.5 vs 4.5, p=0.052), laboratory remission (61% vs 15%, p=0.014), lower BWT (4 vs 5.5 mm, p=0.009) and sonographic response (39% vs 0%, p=0.014) at W14. At the end of induction, we found a fair to good correlation between ITL and HBI (r=-0.430, p=0.009),CRP (r=-0,510, p=0.001), FC (r=-0.590, p=0.001) and BWT (R=-0.506, p=0.002). Receiver operating characteristic (ROC) curve analysis showed that FC at W14 had the largest area under the curve (AUC) in predicting adequate ITL (0.813 vs 0.716 vs 0.739 vs 0.772, p&amp;lt;0.05). Conclusion Patients with higher disease burden measured by ileocolonoscopy at baseline had lower ITL after induction. Adequate ITL were associated with laboratorial remission and sonographic response at the end of induction, with a good correlation with clinical, laboratorial and sonographic parameters. These findings suggest that adequate IFX levels after induction are associated with a better control of inflammation in IBD, so early proactive TDM during induction may be helpful in treatment management.

Fecal Calprotectin in Combination With Standard Blood Tests in the Diagnosis of Inflammatory Bowel Disease in Children.

Introduction: Fecal calprotectin (FC) is a useful non-invasive screening test but elevated levels are not specific to inflammatory bowel disease (IBD). The study aimed to evaluate the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of FC alone or FC in combination with other standard blood tests in the diagnosis of IBD.Methods: Children aged <17 years who had FC (normal range <50 μg/g) measured and underwent endoscopy over 33 months in Christchurch, New Zealand were identified retrospectively (consecutive sampling). Medical records were reviewed for patient final diagnoses.Results: One hundred and two children were included; mean age was 12.3 years and 53 were male. Fifty-eight (57%) of the 102 children were diagnosed with IBD: 49 with Crohn's disease, eight with ulcerative colitis and one with IBD-unclassified. FC of 50 μg/g threshold provided a sensitivity of 96.6% [95% confident interval (CI) 88.3–99.4%] and PPV of 72.7% (95% CI 61.9–81.4%) in diagnosing IBD. Two children with IBD however were found to have FC <50 μg/g. Sensitivity in diagnosing IBD was further improved to 98.3% (95% CI 90.7–99.1%) when including FC >50 μg/g or elevated platelet count. Furthermore, PPVs in diagnosing IBD improved when FC at various thresholds was combined with either low albumin or high platelet count.Conclusion: Although FC alone is a useful screening test for IBD, a normal FC alone does not exclude IBD. Extending FC to include albumin or platelet count may improve sensitivity, specificity, PPV and NPV in diagnosing IBD. However, prospective studies are required to validate this conclusion.