Harvey-Bradshaw Index Score Research Articles

The Role of Ultrasound in Assessment of Disease Activity in Inflammatory Bowel Disease Patients

Abstract Aim This study aim to evaluate the role of Ultrasound in assessment of disease activity in Inflammatory Bowel Disease patients (IBD). Patients and Methods The was performed at Radiology Department and involved a diagnosed cases of Inflammatory Bowel Diseases referred from the Gastroenterology Unit, Ain Shams University Hospitals. A total Thirty six patients inflammatory bowel disease patients (Ulcerative colitis and Chron's disease) were subjected to Intestinal Ultrasound assessment (IUS), Fecal Calprotectin (CP) analysis and calculation of the Clinical Activity Indices. Twenty five patients were subjected to Endoscopic Activity Assessment. Intestinal Ultrasound (IUS) parameters including intestinal wall thickness (BWT) and intestinal bowel wall vascularity, were compared with Endoscopic Activity, Fecal Calprotectin levels (CP) and Clinical Activity Indices. Results Among the thirty-six patients, there were fourteen diagnosed Chron`s cases (38.9%) and twenty-two Ulcerative Colitis cases (61.1%). Roc curve analysis revealed the ability of the ultrasound bowel wall thickness (BWT) to differentiate between mild and moderate disease activity in IBD patients with sensitivity of 90.91% and specificity of 100.0%, with area under curve (AUC) of 0.909 using the endoscopic activity as a gold standard. A statistically significant difference was found between the (BWT) measurements and Simple Endoscopic score (SES-CD) (P = 0.002) as well as between the (BWT) measurements and Endoscopic Mayo score (P = 0.001). A statistically significant correlation was found between the fecal CP levels and Intestinal bowel wall thickness among Ulcerative colitis and Chron's patients with (r = 0.708, P < 0.001) and (r = 0.736, P < 0.01) respectively. There was also statistically significant difference between the Clinical Activity Indices (Harvey-Bradshaw Index and Partial Mayo Score) and the (BWT) among both the Chron's and Ulcerative colitis patients with P-value (0.004) and (0.001) respectively. A statistically significant difference was found between Doppler (Limberg Score) and SES-CD endoscopic activity score (p = 0.009) as well as between Doppler (Limberg Score) and Endoscopic activity Mayo score (p = 0.005). Conclusion The results of the study suggest that the Bowel Wall Thickness (BWT) and Color Doppler Signal could serve as non-invasive parameters of detecting IBD activity. Intestinal US could be one of the promising methods for the detection of the disease activity as well as monitoring of IBD patients.

Short term effectiveness of ustekinumab versus vedolizumab in Crohn's disease after failure of anti-TNF agents: An observational comparative study design with a Bayesian analysis.

Crohn's disease (CD) is a debilitating gastrointestinal disease with complex etiology. Although effective, recipients of anti-tumor necrosis factor (TNF) agents may experience primary or secondary nonresponse, necessitating alternative treatments. This study is intended to compare the short-term effectiveness of ustekinumab and vedolizumab in treating CD after failure of multiple lines of anti-TNF therapy using real-world data. A retrospective study was conducted at a tertiary hospital in Dammam, Saudi Arabia, including adults (≥18 years old) with CD who did not respond to anti-TNF therapy. Primary endpoints were clinical improvement per the Harvey-Bradshaw Index (HBI) scores and remission at 12 weeks on an ordinal outcome scale. Secondary endpoints included clinical, biochemical, and endoscopic remission; clinical response; corticosteroid-free days; and cumulative steroid dose. Proportional odds and logistic regression Bayesian models were used to analyze outcomes, and the probability of treatment effectiveness was calculated from the posterior distribution. The study included 101 patients (ustekinumab, n = 71 and vedolizumab, n = 30) with a median age of 32 years (IQR: 26.0-38.0); 54.4% were male. At 12 weeks, the HBI endpoint showed an adjusted odds ratio (aOR) = 0.60 (95% confidence interval [CI]: 0.25-1.31), favoring ustekinumab, with a 75% probability of treatment effectiveness over vedolizumab. The clinical ordinal scale had an aOR = 0.61 (95% CI: 0.26-1.35) with a 73% probability of effectiveness for ustekinumab. Ustekinumab was also associated with favorable outcomes in secondary endpoints, reaching up to a 90% probability of effectiveness. In CD patients with anti-TNF failure, ustekinumab was more effective than vedolizumab in the short term. These real-world insights contribute to understanding CD management but require validation in larger prospective studies and randomized controlled trials.

Real-world clinical effectiveness of ustekinumab in the treatment of Crohn’s disease in the East Midlands UK

ObjectivesTo evaluate the effectiveness of ustekinumab in treating Crohn’s disease (CD) in a UK real-world setting.DesignThis was a multicentre, retrospective observational study of patients (aged ≥18 years) with CD or...

Relationship between Ustekinumab trough concentrations and clinical, biochemical and endoscopic outcomes in Crohn's disease: A multi-center nationwide retrospective study (TARGET STUDY).

Ustekinumab has been shown to be effective in inducing and maintain clinical and endoscopic remission in Crohn disease (CD). We aim to assess whether ustekinumab trough levels are associated with improved outcomes in CD in real-life. We recruited patients with CD who were treated with ustekinumab for at least 6 months from January 2017 to June 2023. Patients received ustekinumab 6 mg/kg intravenous induction followed by 90 mg every 4-, 8-, or 12-weeks during maintenance were included. We assessed clinical, biochemical, and endoscopic outcomes. Trough concentrations of ustekinumab that were taken from week 42 to week 52 were measured. Primary outcome was to evaluate the relationship between ustekinumab trough concentrations and clinical remission, biochemical normalization, and endoscopic remission. Logistic regression was conducted to assess outcomes. A total of 137 patients with CD, median age of 32 years and 83 (60.6%) males. The median serum levels of ustekinumab measured was 7.2 mcg/mL (interquartile range [IQR] 3.1-9.6). Using Spearman correlation analysis, a strong negative correlation was observed between ustekinumab drug levels and simple endoscopic score (SES-CD) (r = -0.464, P < .001). Additionally, ustekinumab drug levels demonstrated substantial negative correlations with disease severity measured by Harvey-Bradshaw index (HBI) score (r = -0.582, P < .001), C-Reactive Protein (CRP) levels (r = -0.598, P < .001) and fecal calprotectin (FC) levels (r = -0.529, P < .001). A multivariable analysis adjusted for age, sex and body mass index (BMI) showed a significant association between ustekinumab serum drug levels and predefined outcomes. Ustekinumab serum drug level above 4.5 mcg/mL was associated with 24% increase in the likelihood of having an SES-CD score <3 (OR 1.24, confidence interval [CI] 1.12-1.37, P value < .001), 44% more likely to achieve HBI score <5 (OR 1.44, CI 1.26-1.65, P value < .001), 52% higher likelihood of CRP more than 10 (OR 1.52, CI 1.31-1.77, P < .001), and 42% increased likelihood of FC more than 250 (OR 1.42, CI 1.24-1.62, P < .001). Ustekinumab trough concentrations above 4.5 mcg/mL were associated with clinical, biochemical and endoscopic remission in CD. Prospective data is warranted to confirm these findings.

A225 ASSESSMENT OF BEDSIDE INTESTINAL ULTRASOUND IN MONITORING CROHN’S DISEASE ACTIVITY

Abstract Background Bedside intestinal ultrasound (IUS) is an evolving modality in monitoring disease activity and assessing complications in inflammatory bowel disease (IBD). The easy-tolerability and immediate accessibility to results for expedited clinical decision-making contribute to the growing global attraction of IUS integration into IBD care. Fecal calprotectin (FC) is a known, non-invasive tool to assess disease activity in IBD. However, it comes with limitations. Aims To assess the efficacy of IUS in monitoring Crohn’s Disease (CD) compared to FC level. Methods We conducted a retrospective observational study in patients with confirmed CD at a certified IUS gastroenterologist’s outpatient clinic in Saskatoon. Patients’ charts undergoing IUS between February 2022 and April 2023 were reviewed. Patients with CD and available FC results within a month of IUS performance were identified. Age, gender, disease character, clinical symptoms (Harvey-Bradshaw Index (HBI)), FC levels, and IUS bowel wall thickening (BWT) were collected. The cut-off for FC levels and BWT for disease activity were ampersand:003E250 μg/g and ampersand:003E3 mm, respectively. The correlation between IUS BWT and FC levels was analyzed based on the Pearson correlation. Results Among a total of 178 chart reviews, 71 patients were identified. The median age was 49 years, 52.1% were males and 47.8% were females. 35 (49.3%) ileal CD, 35 (49.3%) ileocolonic and 1 (1.4%) colonic CD were identified. The HBI score verified 67.6% mild disease, 19.7% moderate, 11.2% in remission, and 1.4% severe disease. The Pearson correlation coefficient (r) between FC levels and BWT findings on IUS was r = 0.29 (P ampersand:003C0.0001), indicating a weak positive correlation. Conclusions A positive but weak correlation exists between bowel wall thickening in IUS and FC level in monitoring CD. Recognizing FC limitations, future multi-center, larger cohort studies need to be done to investigate this correlation further. Funding Agencies None

IDENTIFICATION OF DISEASE SEVERITY DEFINITIONS FOR ULCERATIVE COLITIS AND CROHN’S DISEASE

Abstract BACKGROUND Evidence suggests that, in patients with ulcerative colitis (UC) or Crohn’s disease (CD), those with moderate disease may achieve better outcomes with vedolizumab than those with severe disease. However, no consensus definition of moderate disease exists for UC or CD, as confirmed by a comprehensive literature review published in 2016.1 We aimed to identify definitions of disease severity for UC and CD in studies published since the approval of vedolizumab. METHODS The first stage of the research comprised a systematic literature review (SLR) that complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement and was registered prospectively with PROSPERO (CRD42023427948). Literature searches were conducted in Embase, MEDLINE, and the Cochrane Library databases on May 16, 2023 to identify publications from 2015 onwards. Title and abstract screening, followed by full-text review was undertaken by two blinded reviewers, with discrepancies resolved by a third reviewer. Data on disease severity indices and thresholds used to define mild, moderate, and/or severe disease were extracted from eligible primary publications. RESULTS Data were extracted from 119 eligible publications (Figure 1), of which 109 related to UC only, 7 to CD only, and 3 to both UC and CD. For UC, the most common disease severity index was Truelove and Witts’ criteria (N = 82), followed by Mayo score or one of its derivatives such as partial Mayo score or Mayo sub-score (N = 29), Lichtiger index (N = 9), Montreal classification (N = 4), Rachmilewitz score (N = 3), and Oxford criteria (N = 3). The definitions identified for mild and moderate disease were similar across studies; however, numerical thresholds used to define moderate and severe disease with Mayo score, partial Mayo score, and Lichtiger index overlapped (Figure 2). For CD, the Crohn’s Disease Activity Index (CDAI) (N = 6) was the most commonly used disease severity index, followed by the Harvey–Bradshaw index (HBI) (N = 2). Moderate disease was defined as a CDAI score of 200–450 or 220–450 or a HBI score of 8–16. CONCLUSION For UC, the thresholds used to define moderate disease were similar across studies but overlapped with those used for severe disease in some cases. Too few CD publications were identified to draw robust conclusions, likely due to the exclusion of those describing patients with mild-to-moderate or moderate-to-severe disease without further stratification in the title or abstract. A targeted literature review of publications reporting phase 3 clinical trials of drugs for UC or CD is ongoing; the thresholds of all measurements used to stratify the patient cohorts in these trials will be extracted to further understand the characteristics of patients with moderate disease. 1. Peyrin-Biroulet L, et al. Clin Gastroenterol Hepatol. 2016;14(3):348-354.e17. Figure 1 PRISMA flow diagram. Figure 2 Numerical ranges used to define mild, moderate, and severe disease for UC.

P859 Sodium Butyrate supplementation significantly improved clinical outcomes and quality of life in patients with Crohn’s Disease – results from a randomized placebo-controlled study

Abstract Background Butyrate has shown anti-inflammatory effects and plays an important role in maintaining gut homeostasis, providing symptomatic relief when orally supplemented in patients suffering from various colonic diseases. Methods In this randomised, double-blind, placebo-controlled study 140 IBD patients in remission or with mild disease (n=60 Crohn's disease, CD and n=80 Ulcerative Colitis, UC) were randomized to oral administration of BLM/placebo for 90 days in addition to conventional therapy. As primary aim: changes in microbiome composition induced by BLM treatment. Fecal microbiota from stool samples was assessed by 16S sequencing. Clinical disease activity assessed by using Harvey Bradshaw Index (HBI) for CD and partial-Mayo Score (pMS) for UC, quality of life assessed by using Inflammatory Bowel Disease Questionnaire 32 (IBDQ-32) and adherence-dietary-raccomandation( WCRF) were evaluated before and after treatment. Results Demographics, clinical and dietary characteristics were similar between the two populations. The microbiota sequencing highlighted two different enterotypes in CD population: the first one was characterized by a low F/B ratio (with a genus prevalence of Fusobacteriota, Alistipes, and Blautia). The second enterotype was characterized by a higher F/B ratio (with a genus prevalence of Escherichia-Shigella and Lachnoclostridium)(Fig1). BLM had a more pronounced effect on enterotype-1 where the taxa associated with intestinal comfort, SCFA production, increased after treatment, while the taxa associated with CRC and intestinal inflammation, decreased. After treatment was observed: a)improved quality of life (IBDQ-32: CD: treat. 170/184 vs Pb. 188/197 p&amp;lt;0.001 vs p=0.021; UC: treat.185/195 vs Pb.188/188 p=0.003 vs p=0.4), b)lower disease activity in CD patients (the HBI score, showed a significant improvement for those treated with BLM as compared to placebo (McNemar’s p=0.013 vs p&amp;gt;0.9).c) reduced Calprotectin levels (Table1.) Finally, a significant separation was observed in samples from patients who have undergone minor surgery (ileo-colon), compared to non-surgery patients. The variable "surgery" seems to be associated with the enterotype-1. Conclusion Sodium butyrate supplementation significantly improved clinical outcomes and quality of life in patients with CD. Our data showed that the differential response to BLM treatment is based on enterotype, suggesting that Enterotype-1 patients may experience greater clinical benefits and improvements in QoL compared to Enterotype-2 patients in both UC and CD populations.

P258 Correlation between patient-reported disease activity, physician’s global assessment and quality of life in Inflammatory Bowel Disease

Abstract Background As a chronic disease, patients’ perspectives on their disease status and quality of life is an essential part of inflammatory bowel disease (IBD) management. Patient reported outcomes should be the standard of measure for signs and symptoms evaluation. We aimed to evaluate the correlation between patients’ self-assessment of disease activity, activity scores and the physician’s global assessment. Methods A unicentric cross-sectional study was conducted. The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) was administered to consecutively evaluated IBD patients in the outpatient setting. Additionally, a pilot questionnaire containing items related to disease activity was also applied to both the patients and the attending physician. Disease activity was categorized as remission, mild, moderate, or severe. Remission was defined as Harvey Bradshaw Index (HBI) ≤ 4 for Crohn's disease or Mayo Clinic Subscore (MCS) ≤ 2 for ulcerative colitis. Correlations between patient's perspective on disease activity, attending physician’s global assessment, activity scores and patient's quality of life were assessed using Spearman’s rank correlation coefficient. Results A total of 105 patients were included (female: 52%; mean age: 44±15 years), of whom 68% had Crohn's disease. 71% percent of patients were receiving biological therapy (table 1). A quarter of the patients (n=27) perceived their disease to be in remission, of whom 56% were indeed in deep remission and 19% in endoscopic remission (table 1). A statistically significant positive correlation was observed between patient self-assessment and HBI scores (mean=2.5±6.5 points, r=0.400, p=0.001) and MCS scores (mean=3.4±4.0 points, r=0.574, p&amp;lt;0.001). Among patients who did not consider themselves in remission, 42% rated the activity of their disease as mild, 23% as moderate, and 9% as severe. The attending physician assessed 26% with mild disease, 22% with moderate disease, and 18% with severe disease (table 1). There was a statistically significant positive correlation between patient and physician assessments (r=0.374; p&amp;lt;0.001). The mean score on the SIBDQ was 28±11 points (table 1), and a statistically significant positive correlation was found between patient self-assessment of disease activity and the SIBDQ (r=0.508, p&amp;lt;0.001). Conclusion These observational data suggest a weak correlation between patient-reported disease activity and the physician’s global assessment. Divergent perceptions of disease activity between patients and physicians may compromise patient-engagement. Furthermore, the moderate correlation observed with overall quality of life supports the importance of alignment patients and physicians to improve the quality of care provided.

P688 Comparative Effectiveness of Ustekinumab Versus Vedolizumab in Treating Crohn’s Disease After Failure of Anti-TNF Agents: Real-World Evidence

Abstract Background Despite effective anti-TNF agents in treating Crohn’s disease (CD), some recipients experience primary or secondary non-responses, requiring alternative options. Ustekinumab and vedolizumab have not been compared in randomized controlled trials (RCTs) among CD population. Thus, we used real-world data to compare ustekinumab and vedolizumab at 12 weeks after failure of TNF inhibitors. Methods A retrospective study was conducted at a tertiary hospital in Dammam, Saudi Arabia. Patients with CD who had not responded to anti-TNF agents and had never been exposed to vedolizumab and/or ustekinumab were included. Children ≤ 18 years of age, naïve CD patients, CD patients using only anti-TNF agents, and patients who lost follow up were excluded. Primary endpoints were clinical improvements, which were measured by Harvey-Bradshaw Index scores at 12 weeks, and clinical remission, which was measured as an ordinal outcome. Remission clinically, biochemically, and endoscopically; clinical response; cumulative steroid dose; and corticosteroid-free days were secondary endpoints. Using probabilistic Bayesian models and proportional odds models, we analyzed outcomes, and the posterior distribution was used to calculate the probability of treatment effectiveness. A national institutional review board approved the study. Results Five hundred forty-six patients received biological agents for inflammatory bowel disease, of whom 101 received biological agents for CD; 71 patients received ustekinumab, and 30 patients received vedolizumab. The baseline characteristics were similar except for perianal disease, which was frequently reported in ustekinumab arm (P = 0.006). Most of the patients were male (54.5%), with a median age of 32 (IQR: 26.0-38.0). Most patients (51.5%) had stricturing disease in the Ileocolonic site (70.3%). For ustekinumab, the median HBI score was 5 (IQR: 3.0 -8.0) whereas for vedolizumab, it was 5 (IQR: 4.0 -7.0). In table 1, a Bayesian multivariable proportional odds model revealed a 40% reduction in median HBI scores at 12 weeks favoring ustekinumab, with an aOR of 0.60 (95% CI: 0.25 to 1.31) and a probability of effectiveness of 75% for ustekinumab. At 12 weeks, the ordinal outcome scale was 39% lower for ustekinumab arm, with an aOR of 0.61 (95% CI: 0.26 to 1.35) and a probability of effectiveness of 73% for ustekinumab arm. Secondary endpoints showed favorable results for ustekinumab reaching up to a 90% probability of effectiveness. Conclusion Among CD patients who failed anti-TNF therapies, ustekinumab was more effective than vedolizumab. To validate these results and determine these treatments’ relative efficacy in managing CD, further investigations, including prospective studies and RCTs, are essential.

P137 Salivary calprotectin: a potential biomarker in inflammatory bowel disease?

Abstract Background Background: Biomarkers are used frequently for evaluation and monitoring of IBD. Fecal calprotectin (FCP) is an already established biomarker in IBD, nevertheless patients often do not feel comfortable with stool manipulation. A saliva sample collection is particularly interesting due to its noninvasiveness and readiness of collection. We aimed to assess if salivary calprotectin (SCP) could be used as a new biomarker to assess disease activity. Methods In this observational cohort study, saliva was collected through the passive drool technique from adult IBD patients. All patients were submitted to a previous oral examination performed by a dentist. Recent history of antibiotic treatment (within the preceding month), proton pump inhibitors or non-steroidal anti-inflammatory drugs were exclusion criteria. Determination of FCP and SCP levels was accomplished using Elia Stool Extraction Kit and Elia Calprotectin 2 test. Intestinal disease activity was assessed with fecal calprotectin levels and the Harvey-Bradshaw Index (HBI) or Partial Mayo score (PMS). Ethical approval was obtained. Results 92 patients (56 with CD and 36 with UC) were included. Clinical characteristics are presented in Table 1. Patients had a median FCP of 45 mg/Kg and a median SCP of 206.5 mg/Kg. No significant correlations between SCP and FCP, CRP (C-reactive protein), ferritin and ESR (erythrocyte sedimentation rate) were found. However, there was a significant correlation between fecal calprotectin and CRP (p&amp;lt;0.001) and ESR (p=0.011). Disease activity scores did not correlate significantly with SCP, although there was a significant correlation between FCP and PMS (p=0.006). IBD patients were stratified based on a composite criterion for inactive disease HBI score &amp;lt;5 for CD or a PMS ≤ 2 for UC, and FCP cutoff value of 150 mg/Kg), with no significant difference in SCP between the two groups, despite the significant difference in FCP (p&amp;lt;0.001). No significant differences between different treatments groups or no treatment in salivary calprotectin concentration were found using Kruskal–Wallis H tests (CD (χ2(4) = 6.211, p = 0.184; UC group (χ2(3) = 1.201, p = 0.753)). 77% of patients with IBD do not have periodontal health. Nonetheless, there was no significant difference in the median SCP value between patients with or without periodontal health. Although the median SCP value was higher in patients with UC without periodontal health, the difference was not statistically significant (0.484). Conclusion SCP does not correlate with FCP and do not represent a reliable biomarker to distinguish disease activity in patients with IBD patients. Moreover, according to our results, it cannot be used as a marker of lack of oral health, namely periodontitis.

P903 Persistence, efficacy and tolerance of subcutaneous Infliximab after switch from intravenous infliximab in IBD patients in remission: one-year results from a multicenter prospective cohort

Abstract Background Prospective data after switch from intravenous infliximab (IV-IFX) to subcutaneous (SC-IFX) in Inflammatory Bowel Disease (IBD) is needed. The aim of this prospective multicenter cohort was to describe SC-IFX persistence, efficacy and tolerance after switch from IV-IFX. Methods IBD patients in steroid-free clinical remission (defined by a Harvey Bradshaw index (HBI) ≤ 4 for Crohn’s disease (CD), and partial Mayo Score (PMS) ≤ 2 with no subscore &amp;gt;1 for ulcerative colitis UC)) for at least 6 months on IV-IFX, were enrolled in this prospective cohort if they switched to SC-IFX. Clinical (HBI, PMS), biological (CRP, fecal calprotectin (FC)) and pharmacokinetic evaluations were performed at 3, 6, 12 and 24 months from switch. In case of clinical or biological relapse, as per physicians’ judgement, SC-IFX dose could be increased, or drug changed. Primary endpoint was SC-IFX persistence at week 48 (W48). Secondary endpoints comprised steroid-free clinical remission at W48, proportion of patients who switched back to IV-IFX, HBI and PMS changes and FC, CRP and infliximab serum level changes. Statistical comparisons were performed using Fisher’s exact test. Survival without treatment discontinuation was analysed using a Kaplan-Meyer curve. Results 426 patients were included (72.4% CD, 45.1% female, median age 37 years), with a median time from diagnosis of 143 months in CD, 154 months in UC. At baseline, 74% were on IV-IFX standard dose (5mg/kg every 8-week) and 68 (16%) received combination therapy with an immunosuppressant. Among patients with complete data until W48, SC-IFX persistence was 95.3% (CI, 93.2-97.5). 319/367 (89.9%) were on steroid-free clinical remission. From baseline to W48, median HBI and PMS scores were 0, CRP did not change significantly, median FC rate decreased significantly from 52µg/g to 36 µg/g (p=0.015). Mean Infliximab trough level at inclusion was 7.97µg/mL, while it reached 17.96µg/mL at W48 (p&amp;lt;0.0001). 23 (5.4%) patients had an increase of SC-IFX dose and 22 (5.2%) stopped SC-IFX, of which 6 patients switched back to IV-IFX. SC-IFX persistence was significantly higher among patients treated with SC-IFX monotherapy (98.8%) as compared to those on combination therapy (90.0%) (HR=0.14 [0.04-0.53]). Adverse events were reported in 181/426 patients (42.4%), 12 led to treatment discontinuation. Nine severe adverse events (2%) were reported. Three patients (0.7%) had IBD-related surgery and 8 (1.9%) IBD-related hospitalization. Conclusion In this large multicenter prospective cohort of IBD patients in remission, one-year persistence of SC-IFX after switch from IV-IFX was 95.3%, supporting excellent efficacy and tolerance of SC-IFX.

PHASE ANGLE AS A PREDICTOR OF MUSCLE MASS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE.

Malnutrition/sarcopenia is frequent in patients with inflammatory bowel diseases (IBD), and results in muscle catabolism, impacting treatment response, postoperative complications, and quality of life. This study aims to assess whether the phase angle (PhA) is a parameter for predicting reduced muscle mass in patients with IBD. Adult patients with IBD were included in this cross-sectional study. For the estimation of muscle mass and the calculation of the PhA, we used bioelectrical impedance analysis (BIA). Crohn's disease (CD) and ulcerative colitis (UC) activity scores were defined using the Harvey-Bradshaw index and partial Mayo score, respectively. The area under the ROC curve was calculated to identify the PhA cut-off point for reduced muscle mass. The sample consisted of 145 patients, with 39 (26.9%) with IBD in the active phase. There was a correlation of the PhA with skeletal muscle mass (SMM) (rs 0.35, P<0.001) and with the skeletal muscle mass index (SMI) (rs 0.427, P<0.001), and the associations remained in the most active form (moderate or severe) of IBD. The ROC curve analysis indicated that the cut-offs points of the PhA ≤5.042 for female and PhA ≤6.079 for male can be used to predict muscle mass reduction. The PhA can be considered a predictor of muscle mass reduction in IBD patients, and we can use it for screening and monitoring the evolution of malnutrition. • This study aims to assess whether the phase angle is a parameter for predicting reduced muscle mass in patients with inflammatory bowel disease. • There was a correlation of the phase angle with skeletal muscle mass and the associations remained in disease activity. • The ROC curve analysis indicated that the cut-off point of the PhA ≤5.042° for women and PhA ≤6,079° for men can be used to predict muscle mass reduction. • The phase angle can be considered a predictor of muscle mass reduction in inflammatory bowel disease.

Rapid assessment of malnutrition based on GLIM diagnosis in Crohn's disease.

Malnutrition is strongly linked to adverse outcomes in patients with Crohn's disease (CD). In this study, our objective was to validate the Global Leadership Initiative on Malnutrition (GLIM) criteria and develop a fast and accurate diagnostic approach for identifying malnutrition in CD patients. This study assessed 177 CD patients from four general hospitals. The efficacy of the GLIM criteria for the diagnosis of CD malnutrition was compared. By analyzing the independent factors, a nomogram model was derived and internally validated to predict the diagnosis of malnutrition in patients with CD. Model performance was assessed using discrimination and calibration, decision curves, and net benefit analyses. Compared with the SGA criteria, the GLIM criteria was consistent in sensitivity (88.89%) and specificity (78.43%) [AUC = 0.84; 95% Confidence Interval (CI): 0.77-0.89]. The Harvey-Bradshaw index(HBI) score (OR: 1.58; 95% CI: 1.15-2.18), body mass index (OR: 0.41; 95% CI: 0.27-0.64), and mid-upper arm circumference (OR: 0.68; 95% CI: 0.47-0.9) were independent factors associated with malnutrition. The nomogram was developed based on these indicators showing good discrimination in malnutrition diagnosis (AUC = 0.953; 95% CI: 0.922-0.984), with agreement after calibration curve and decision curve analysis. The GLIM criteria are appropriate for diagnosing malnutrition in CD patients. The HBI score may be used to diagnose malnutrition in patients with CD and become a possible selection for the GLIM etiologic criteria of inflammation. The HBM nomogram could be a simple, rapid, and efficient method for diagnosing malnutrition in CD patients.

Real-World Effectiveness of Vedolizumab vs Anti-TNF in Biologic-naïve Crohn's Disease Patients: A 2-year Propensity-score-adjusted Analysis from the VEDOIBD-Study.

The aim of this observational, real-world evidence, modified intention-to-treat (mITT) study based on prospectively collected data from the VEDOIBD registry was to compare the effectiveness of vedolizumab (VEDO) vs antitumor necrosis factor (anti-TNF) in biologic-naïve Crohn's disease (CD) patients. Between 2017 and 2020, 557 CD patients starting therapy with VEDO or anti-TNF were consecutively enrolled in 45 IBD centers across Germany. Per study protocol, the analysis excluded biologic-experienced patients and those with a missing Harvey-Bradshaw Index score, resulting in a final sample of 327 biologic-naïve CD patients. Clinical remission was measured using the Harvey-Bradshaw Index at the end of induction therapy and after 1 and 2 years. Switching to a different therapy was considered an outcome failure. Propensity score adjustment with inverse probability of treatment weighting was used to correct for confounding. The effectiveness of both VEDO (n = 86) and anti-TNF (n = 241) was remarkably high for induction treatment, but VEDO performed significantly less well than anti-TNF (clinical remission: 56.3% vs 73.9%, P < .05). In contrast, clinical remission after 2 years was significantly better for VEDO compared with anti-TNF (74.2% vs 44.7%; P < .05; odds ratio, 0.45; 95% CI, 0.22-0.94). Remarkably, only 17% of patients switched from VEDO to another biologic vs 44% who received anti-TNF. The results of this prospective, 2-year, real-world evidence study suggest that the choice of VEDO led to higher remission rates after 2 years compared with anti-TNF. This could support the role of VEDO as a first-line biologic therapy in CD.

Quality of Life (QoL) in Patients with Chronic Inflammatory Bowel Diseases: How Much Better with Biological Drugs?

Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic and disabling diseases that affect patient health-related quality of life (HRQoL). IBD patients are frequently exposed to high levels of stress and psychological distress. Biological drugs have been proven to reduce inflammation, hospitalization, and most of the complications that characterize IBDs; their potential contribution to patients' HRQoL remains to be explored. To evaluate and compare any change in the HRQoL and markers of inflammation in IBD patients undergoing biological drugs (infliximab or vedolizumab). A prospective observational study was conducted on a cohort of IBD patients, aged >18 years, who were prescribed with infliximab or vedolizumab. Demographic and disease-related data at baseline were collected. Standard hematological and clinical biochemistry parameters, including C-reactive protein (CRP), white blood cells count (WBC), erythrocytes sedimentation rate (ESR), and α1 and α2 globulins were measured after a 12-h fast at baseline (T0), after 6 weeks (T1), and at 14 weeks (T2) of biological treatment. Steroid use, disease activity as measured by the Harvey-Bradshaw index (HBI) and partial Mayo score (pMS) for the CD and UC, respectively, were also recorded at each timepoint. The Short Form 36 Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT-F), and Work Productivity and Activity Impairment-General Health Questionnaire (WPAI:GH) were administered to each patient at baseline, T1, and T2 to address the study aims. Fifty eligible consecutive patients (52% with CD and 48% with UC) were included in the study. Twenty-two patients received infliximab and twenty-eight received vedolizumab. We noted a significant reduction in the CRP, WBC, α1, and α2 globulins from T0 to T2 (p = 0.046, p = 0.002, p = 0.008, and p = 0.002, respectively). Participants showed a significant decrease in steroid administration during the observation period. A significant reduction in the HBI of CD patients at all three timepoints and a similarly significant decrease in the pMS of UC patients from baseline to T1 were recorded. Statistically significant changes were observed in all questionnaires during follow-up as well as an overall improvement in the HRQoL. The interdependence analysis carried out between the biomarkers and the scores of the individual subscales showed a significant correlation between the variation (Δ) of the CRP, Hb, MCH, and MCV with physical and emotional dimensions of the SF-36 and FACIT-F tools; work productivity loss expressed by some of the WPAI:GH items negatively correlated with the ΔWBC and positively with the ΔMCV, ΔMCH, and Δ α1 globulins. A sub-analysis according to the type of treatment showed that patients receiving infliximab experienced a more pronounced improvement in their HRQoL (according to both SF-36 and FACIT-F) compared with patients receiving vedolizumab. Both infliximab and vedolizumab played an important role in contributing to the improvement of the HRQoL in IBD patients by also reducing inflammation and, consequently, steroid use in patients with an active disease. HRQoL, being one of the treatment goals, should also be assessed when taking charge of IBD patients to assess their clinical response and remission. The specific correlation between the biomarkers of inflammation and life's spheres, as well as their possible role as clinical markers of HRQoL, should be further investigated.

Pretreatment serum monocyte chemoattractant protein-1 as a predictor of long-term outcome by ustekinumab in patients with Crohn's disease.

Ustekinumab has been proven to be effective for treatment of patients with Crohn's disease; however, 30-40% of patients have been reported to lose clinical response within 2years. We aimed to evaluate the efficacy of ustekinumab and identify predictors of short-term and long-term efficacy in Crohn's disease. Patients with Crohn's disease receiving their first ustekinumab infusion in our hospital between June 2017 and September 2020 were prospectively enrolled. Concentrations of serum cytokines and chemokines were measured using a multiplex bead array assay. Fifty-nine Crohn's disease patients were enrolled in this study. Among 34 clinically active patients, 38.2% achieved a clinical response at week 8. None of the assayed factors were associated with short-term clinical response. Cumulative persistence rates of ustekinumab were 77.6% at 1year and 58.9% at 2years. Univariate Cox regression analysis revealed that Harvey-Bradshaw Index scores at baseline, concomitant immunomodulator treatment, and concentrations of interferon gamma-induced protein-10, monocyte chemoattractant protein-1 (MCP-1), and interleukin (IL)-1RA, IL-4, IL-6, and IL-8 were significantly associated with loss of efficacy. Multivariate Cox regression analysis found that biologic naïve status (hazard ratio [HR]: 0.1191, 95% confidence interval [CI]: 0.02458-0.5774) and MCP-1 concentrations (HR: 1.038, 95% CI: 1.015-1.062) were significantly and associated with loss of sustained efficacy for ustekinumab treatment. Our findings suggest that pretreatment serum MCP-1 analysis, combined with a history of biologic use, could be a novel biomarker for predicting the long-term efficacy of ustekinumab in patients with Crohn's disease.

P705 Switching from intravenous to subcutaneous infliximab: clinical and patient experience outcomes

Abstract Background Intravenous (IV) infliximab (IFX) monotherapy is associated with significant loss of response. Therapeutic drug monitoring shows an association with low serum trough drug levels and development of anti-IFX antibodies. Combination therapy with immunomodulators is not always possible, and IFX dose escalation leads to higher drug costs and time pressure on infusion units. Both approaches have raised heightened patient safety concerns due to the Covid-19 pandemic. Subcutaneous (SC) IFX pharmacokinetics lead to improved drug trough levels, which could lead to better clinical outcomes. Methods The NHS Greater Glasgow and Clyde biologics database was used to identify selected patients currently treated with IV IFX for IBD for suitability for SC switch. Patients were contacted to allow informed choice to opt in or out of switch. Baseline clinical data was collected, and patients were reviewed at week 8 and week 24 for assessment of clinical disease activity scores, IFX trough levels/anti-drug antibody levels, and faecal calprotectin. Patient experience outcomes were assessed using a quality of life questionnaire (CUCQ-8). Results 31 patients consented to switch; F:M = 17:14. The majority of patients (16) had Crohn’s disease, with 13 with UC and 2 IBDU. Mean duration of disease was 9.1 years and duration of prior IV therapy was 3.3 years. 28 patients were reviewed at week 8 and 24 at week 24. At week 24, 71% of patients were in clinical remission (Harvey-Bradshaw index score &amp;lt;5 or partial Mayo score &amp;lt;2), 96% had CRP &amp;lt;5 mg/Land 87% had FCP &amp;lt;250µg/g. 21% of patients had subtherapeutic IFX trough levels at baseline, all had increased by week 8 and there were no subtherapeutic levels measured by week 24. One patient had detectable antibodies at week 24, compared with 9 patients at baseline. Three patients required oral steroid therapy during the 24-week follow up period. There were no hospital admissions, significant infections or adverse reactions within the cohort. 15 patients submitted CUCQ-8 scores, of these 7 patients’ scores had worsened at week 8 but by week 24 13/15 were stable or improved compared to baseline. Conclusion Switching from IV to SC infliximab is welcomed by most patients. The efficacy, tolerability, increased drug level and safety which has previously been demonstrated is reproduced in our cohort. This study is the first to explore patient experience outcomes. The finding of initial worsening of the CUCQ-8 score, but overall improvement by week 24 opens further opportunity for engaging patient involvement in switch programmes.

P643 Psoriasis induced by anti-TNF therapy in Inflammatory Bowel Disease: analysis of therapeutic management and evolution of both diseases in a nationwide cohort study

Abstract Background Some patients with Inflammatory Bowel Disease (IBD) who are treated with anti-TNFα therapy develop a drug-induced psoriasis (IP) as an adverse event. There are some therapeutic approaches, being more frequent to change the biologic therapy to ustekinumab, effective and approved for the treatment of both entities. This could be the best option, but available data are lacking and it could increase the risk of IBD relapse. Our aim is to assess the management of anti-TNF IP in IBD, and the subsequent evolution of both diseases in a large nationwide cohort of patients. Methods Retrospective, observational multicenter study from the prospectively maintained Spanish ENEIDA registry. Participants were patients with IBD and anti-TNFα IP. At baseline, psoriasis severity was classified as mild, moderate or severe, and remission was defined as the resolution of skin lesions, clinical response as an improvement without complete resolution, and no response as the absence of improvement. IBD clinical activity was defined based on Harvey-Bradshaw Index and Partial Mayo Score. All items were evaluated when available at baseline and 16, 32 and 54 weeks. Results Anti-TNFα IP was reported in 234 patients (CD: 185, UC: 46, unclassified IBD: 3). SWAP strategy was chosen in 76 patients (32.5%), most of them to ustekinumab (90.8%), 71 (30.3%) patients continued anti-TNF, 49 (20.9%) discontinued it, and in 38 (16.2%) a switch to a second anti-TNF was made. The decision to continue or not anti-TNF was associated to psoriasis severity (p&amp;lt;0.001) and baseline IBD activity (p=0.03). In mild psoriasis, anti-TNF was continued in 56.81% of patients, whereas SWAP and withdrawal of the anti-TNF were the most used in moderate and severe disease (32.3% and 36.5% respectively). SWAP strategy was also the most used in active IBD (46%). During follow-up, CD activity got worse in anti-TNF withdrawal group (p=0.003), without differences in the other groups. Regarding to psoriatic lesions, all strategies showed a significant improvement, with worse results when anti-TNF was continued (remission rate of 58%, p=0.042), and without differences between the other strategies at week 54. In multivariate analysis, male gender was associated with IBD remission (HR 0.233; IC95% 0.061-0.894). Trunk (OR 2.777; IC95% 1.120-6.889), as well as palms and soles location (OR 2.091; IC95% 1.018-4.294), and stopping anti-TNF treatment (OR 3.010; IC95% 1.110-8.159), were independently associated with remission of skin lesions. Conclusion Evaluating IBD activity and psoriasis severity is essential before modifying IBD treatment due to IP. Continuing anti-TNF treatment in mild psoriasis cases, and considering SWAP to ustekinumab in moderate-severe ones, could be a suitable strategy.

P644 Leucine-rich alpha 2 glycoprotein- A useful biomarker to discriminate small intestinal mucosal healing in asymptomatic CRP-negative Crohn’s disease

Abstract Background The long-term treatment goals for inflammatory bowel disease including Crohn’s disease (CD) have shifted from clinical remission to mucosal healing. However, frequent endoscopies are a great burden on the patients. Leucine-rich alpha 2 glycoprotein (LRG) is produced by hepatocytes, neutrophils, and the intestinal epithelium. Therefore, it is speculated to be more gut-specific than C-reactive protein (CRP) level. This study examined whether LRG could be used as a biomarker to determine the presence or absence of small intestinal mucosal healing in asymptomatic patients with CRP-negative CD. Methods The subjects of this study were asymptomatic CRP-negative CD patients who visited our department from May 2021 to October 2022, had their LRG measured, and underwent imaging evaluation by capsule endoscopy or balloon-assisted endoscopy. We analysed the patients’ clinical background, the ROC-AUC of LRG for mucosal healing, the cut-off value of LRG to discriminate mucosal healing. Endoscopic evaluation was performed within 3 months before and after the LRG measurement. Mucosal healing was defined as the absence of open ulcers. Clinical remission (no subjective symptoms) was defined as a Harvey-Bradshaw index (HBI) ≤4 points. The upper limit of the normal CRP value was set to &amp;lt;3 mg/L. Results A total of 28 cases were analysed; 13 (46%) were men. The median age (range) of onset was 21.2 years (7-52 years). The median disease duration (range) was 6.4 years (0-27). B1 was established in 13 (45%) cases, B2 in 7 (25%) cases and B3 of Montreal Classification in 8 (29%) cases. The median (range) of the HBI score was 2 (0-4). The median (range) of LRG was 12.3 g/ml (7.6-20.5 μg/ml). The ROC-AUC of LRG for mucosal healing was 0.743 (95% confidence interval 0.559-0.927). The cut-off value of LRG for discriminating mucosal healing was 12.2 μg/ml (sensitivity 0.769, specificity 0.682). Conclusion In asymptomatic CRP-negative CD patients, when LRG was 12.2 μg/ml or more, it was suggested that they might have small intestinal ulcers.

Validation of the German version of the Short Health Scale - a brief, valid and reliable instrument to assess health-related quality of life in German-speaking patients with inflammatory bowel diseases.

Health-related quality of life (hrQoL) may be the most important patient-reported outcome for patients with chronic disorders. The Short Health Scale (SHS) is a brief four-item instrument to assess hrQoL in patients with bowel disorders. This study examined the validity, reliability and sensitivity of the German translation of the SHS in a cohort of outpatients with inflammatory bowel diseases (IBD). The study was preregistered in April 2021 (https://doi.org/10.17605/OSF.IO/S82D9). Outpatients with IBD (n=225) in different stages of disease activity (as determined by the Harvey-Bradshaw index or partial Mayo score) completed the German SHS and the short Inflammatory Bowel Disease Questionnaire (sIBDQ) as an established measure of hrQoL to examine the convergent validity. To assess reliability, a subset of patients (n=30) in remission completed the same questionnaires after 4-8 weeks. Sensitivity to change was established from questionnaires of patients with either decreased (n=15) or increased (n=16) disease activity after 3-6 months. The internal consistency of the German SHS was high (Cronbach's α=0.860). SHS total scores correlated strongly with sIBDQ scores (ρ=-0.760, p<0.001) and disease activity (ρ=0.590, p<0.001). Retest reliability was high (ρ=0.695, p<0.001). Sensitivity to change was statistically significant for patients with decreased (p=0.013) but not increased (p=0.134) disease activity. The German version of the SHS is a valid and reliable tool to measure hrQoL in persons with IBD.