Inflammatory Bowel Disease Clinical

Background Acute Severe Ulcerative Colitis (ASUC) is a medical emergency, with limited therapeutic options available for medical management. Tofacitinib and Upadacitinib are novel Janus Kinase inhibitors (JAKi), with proven efficacy for ulcerative colitis (UC). This study aimed to examine the outcomes of patients treated with JAKi for ASUC in a real-world population. Methods A retrospective multi-centre study was conducted including patients (≥18 years) with ASUC commenced on Tofacitinib or Upadacitinib from April 2021 to April 2024. ASUC was defined according to Truelove and Witt’s criteria. Demographic and clinical data were recorded at admission, JAK induction, discharge, week 8, week 16 and 1 year post-induction. The primary outcome was need for colectomy. We further evaluated adverse events and drug-specific response. Results A total of 124 patients were included from 11 Australian Inflammatory Bowel Disease (IBD) centers. Tofacitinib was used in 49%, while Upadacitnib was used in the remainder. 58% of patients received JAKi as first line salvage therapy, while the remainder received JAKi sequentially after failure of first line infliximab therapy. The rate of colectomy during admission was 17% and 40% by 1 year. There was no significant difference between rate of colectomy during index admission (p=0.38), or 1 year post induction (p=0.24) between Tofacitinib and Upadacitinib. There was a significantly increased risk of inpatient colectomy for those receiving sequential salvage compared to initial JAKi salvage (p=<0.01). However, there was no significant difference in the rate of colectomy in either cohort up to 1 year post induction (p=0.19). Clinical response was observed in 45% of patients by day 3 of induction and 65% by day 7. Clinical remission rates were 40% by week 8 and 65% by week 16. Biochemical remission was achieved in 51% by week 16. Mucosal healing was achieved in 47% of patients who underwent repeat endoscopy within 16 weeks of induction. Adverse events occurred in 16% of patients, all of which were minor and did not require hospitalisation. The most common events noted were acne (7%) and nasopharyngitis (6%). Conclusion Jaki demonstrate effectiveness and safety for the management of ASUC. There was no significant difference in the inpatient colectomy rate between Tofacitinib and Upadacitinib. There was a significantly higher rate of inpatient colectomy for patients requiring sequential salvage therapy, but no significance when patients were followed up to 1 year. There is variability in prescribing practice between dosage of Tofacitinib and Upadacitinib, duration and dosage of corticosteroid wean, and the use of prophylactic PJP and VTE prophylaxis.

Background Obesity represents a chronic inflammatory state that may influence the pathogenesis and clinical progress of Inflammatory Bowel Disease (IBD). Its role on treatment response remains complex and multifactorial.1 This study aimed to assess the prevalence of obesity and its impact on clinical and endoscopic outcomes in IBD patients undergoing biologic therapy. Methods This is a prospective study carried out at a tertiary hospital center in Albania including IBD patients under biologic therapy with adalimumab, intravenous infliximab, and vedolizumab. Demographic laboratory and clinical data [age, gender, body mass index (BMI), disease location, extent, activity and duration] were collected. Endoscopic activity was assessed using the Mayo endoscopic sub score for ulcerative colitis (UC) and the Simple Endoscopic Score for Crohn’s Disease (SES-CD). Clinical remission was defined as a total Mayo score ≤2 for UC and a Crohn’s Disease Activity Index (CDAI) <120 for CD. Mucosal healing (MH) was defined as a Mayo endoscopic sub score of 0–1 for UC and an SES-CD ≤2 for CD. Patients were stratified by BMI into non-obese (18.5–29.9 kg/m²) and obese (≥30 kg/m²) groups. The primary outcomes were steroid-free clinical remission and MH at week 52. All analyses were performed with IBM SPSS Statistics version 27.0. Results A total of 131 IBD patients were included (mean age 45.3 ± 15.5 years), 51.1% male. Mean disease duration was 8.5 ± 7.0 years, and mean age at diagnosis was 37.2 ± 12.8 years. 17% of patients were obese. Obesity was significantly associated with lower steroid free clinical remission at week 52 (20% vs 59%; χ²=4.77, p = 0.029; Fisher’s p = 0.038). MH was less frequent in obese individuals, with significantly higher mucosal activity scores at week 52 (χ² = 4.19, p = 0.041; Fisher’s exact p = 0.043). Among laboratory biomarkers, only CRP levels were found higher in obese patients compared with non-obese patients (16.96 vs.7.42 mg/L), although it didn’t reach statistical significance (p = 0.136). Conclusion Obesity was present in 17% of our IBD cohort and was significantly associated with poorer clinical outcomes, including reduced rates of remission and mucosal healing at week 52. These findings highlight the need for targeted weight management strategies in this subgroup. Encouraging weight loss in obese IBD patients may not only enhance general health but also improve therapeutic response and long-term disease control. Reference: 1. Peraza, J., Abbott, E., Shneyderman, M. et al. The Rising Epidemic of Obesity in Patients with Inflammatory Bowel Disease. Curr Treat Options Gastro 22, 134–144 (2024). https://doi.org/10.1007/s11938-024-00453-5 Conflict of interest: Dr. Sina, Marsela: No conflict of interest Pemaj, Xhensila: No conflict of interest Prifti, Skerdi: No conflict of interest Mullaj, Rubin: No conflict of interest Telaku, Skender: No conflict of interest

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Objective: To determine the correlation between inflammatory markers (fecal calprotectin and CRP) and Simple Endoscopic Score for Crohn's Disease (SES-CD) in patients with Crohn's disease. Study Design: Cross-sectional study. Setting: Department of Medicine, Liaquat University of Medical and Health Sciences. Period: 24th August 2024 to 24th February 2025. Methods: Thirty-three patients with endoscopically diagnosed Crohn's disease were enrolled. Blood samples for CRP and first-morning stool samples for fecal calprotectin were collected. SES-CD was calculated during endoscopic evaluation. Demographic and clinical data were recorded using standardized proformas. Spearman's correlation coefficient was used to assess relationships between variables. Results: The study included 33 patients with a median age of 44.00 years (IQR: 34.00-52.50) and mean BMI of 25.86 ± 2.30. The median SES-CD score was 8.00 (IQR: 6.00-13.00), and mean CRP level was 14.00 ± 6.48 mg/L. Spearman correlation analysis revealed strong positive correlations between SES-CD and both fecal calprotectin (ρ = 0.994, p < 0.001) and CRP levels (ρ = 0.993, p < 0.001). A significant correlation was also found between SES-CD and BMI (ρ = 0.882, p < 0.001). No significant correlations were observed between SES-CD and age (ρ = 0.048, p = 0.791), gender (ρ = -0.102, p = 0.571), or disease duration (ρ = -0.017, p = 0.925). Conclusion: Both fecal calprotectin and CRP demonstrated strong correlations with endoscopic disease activity in Crohn's disease, suggesting their potential utility as reliable non-invasive biomarkers for monitoring disease severity and guiding treatment decisions.

Introduction: In patients with Inflammatory Bowel Diseases (IBD) there is an increased risk of Cytomegolovirus (CMV) infection possibly due to malnutrition and immunosuppressive medication. There are other risk factors such as advanced age and disease duration more than 5 years. Moreover, there is evidence that CMV infection increases colectomy rates. Anti-viral treatment in CMV infection in IBD patients is controversial. In this study, we aimed to define the CMV infection effect on IBD course. Methods: Patients with IBD who had positive serum CMV-DNA (> 42 copies/ml) between 2013 and 2016 were identified in Ankara University IBD cohort. Patient charts were reviewed retrospectively. We identified 75 patients with positive serum CMV-DNA. Patient demographics, colectomy rates, medication types, mortality rates were abstracted from database retrospectively. Results: Out of 78 patients, 66 patients had Ulcerative Colitis (UC) (88%). Mean age of patients was 39.4 years. 54 % of UC patients had either extensive disease or pancolitis. There was no correlation between age, gender, leucocyte count, crp levels, hemoglobin levels and either mortality or colectomy. CMV viremia did not lead to colectomy. However, in patients who had clinical events (colectomy or mortality), median serum CMV-DNA level was 1038 copies/ml whereas in patients who had spontaneous remission, median serum CMV-DNA level was 182 copies/ml (p value: 0.006). There were higher mortality and colectomy rates in patients with serum CMV DNA levels > 1000 copies/ml (p value: 0.032). Trombosis was found to be an independent risk factor for mortality and colectomy (%95 CI: 19.3 (1.9-188);P:0.011). Steroid use was found to be in 82% of the patients. There was no correlation between steroid use and mortality or colectomy rates. Conclusion: Serum CMV-DNA levels more than 1000 copies/ml increases the colectomy rates in IBD patients. Steroid use seems not to be a factor increases colectomy rate in this cohort. Thrombosis is an independent risk factor for colectomy and mortality in IBD patients with CMV infection.

We aimed to identify early noninvasive predictors of clinical and endoscopic remission in children with Crohn disease (CD) under infliximab (IFX). Prospective observational study conducted in children with moderate-to-severe CD starting IFX. All patients underwent weighted pediatric CD activity index (wPCDAI) assessment, C-reactive protein and fecal calprotectin (FC) at week 0, 14, and 48. Endoscopy was performed at 0 and 48 weeks. The primary outcome was to determine the ability of 14-week wPCDAI, C-reactive protein, and FC to predict 1-year steroid-free clinical remission and mucosal healing. As a secondary outcome we evaluated their concordance with Simple Endoscopic Score for CD (SES-CD) at week 48. Forty-one children were enrolled. At 1 year, 21 (51%) and 16 (39%) were in clinical and endoscopic remission. Only combined postinduction FC and wPCDAI were able to predict 1-year clinical and endoscopic remission (hazard ratio 4.81 [95% confidence interval 1.76-20.45], P = 0.05 and hazard ratio 5.51 [95% confidence interval 1.83-26.9], P = 0.03). One-year SES-CD moderately correlated with FC (r = 0.52; P = 0.001). The FC cut-off value for mucosal healing was 120.5 μg/g (area under the curve 0.863, 83% sensitivity, 75.5% specificity; P = 0.005). The concordance between wPCDAI and SES-CD was excellent and good for severe disease and remission (k 0.87 and 0.76). Post induction FC combined with wPCDAI can predict 1-year clinical and endoscopic response to IFX in pediatric CD. FC shows a moderate correlation with SES-CD, whereas wPCDAI has a good concordance with endoscopic remission or severe disease, but not with mild and moderate disease.

Validation of Endoscopic Activity Scores in Patients With Crohn's Disease Based on a Post Hoc Analysis of Data From SONIC

AGA Clinical Practice Update on Management of Inflammatory Bowel Disease in Elderly Patients: Expert Review

Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease. While endoscopy is the gold standard for assessing activity, its invasiveness limits routine application. Fecal calprotectin (FC) offers a non-invasive alternative, but validated cut-offs for endoscopic activity, disease extent, and acute severe UC (ASUC) are lacking. This study aims to establish validated FC cut-offs using internal and external cohorts and to explore their relationship with disease extent and ASUC Methods This multicenter study consecutively enrolled 330 UC patients from five centers, dividing them into a 270-patient internal training cohort and a 60-patient external validation cohort. FC’s performance in differentiating endoscopic activity (Mayo subscore) was evaluated via ROC analysis. Exploratory analyses employed ordinal logistic regression to link FC with disease extent (Montreal E1/E2/E3) and the Mann-Whitney U test to compare FC levels between severe activity and ASUC patients, both within the internal cohort. Results In the internal training cohort, FC demonstrated excellent diagnostic performance in differentiating endoscopic activity grades. For detecting clinically significant endoscopic activity (Mayo endoscopic subscore ≥1), the AUC was 0.957 (95% CI: 0.931–0.983). A set of FC cut-offs was established: 97.5 μg/g for distinguishing remission from activity (sensitivity 90.1%, specificity 100%), 309.5 μg/g for distinguishing mild from moderate-to-severe activity (sensitivity 86.3%, specificity 91.7%), and 938 μg/g for distinguishing moderate from severe activity (sensitivity 88%, specificity 74.1%). These cut-offs showed consistent diagnostic performance in both the internal and external validation cohorts. Exploratory analyses revealed no independent correlation between FC levels and disease extent after adjusting for endoscopic activity (P > 0.05). Notably, the FC assay’s upper detection limit (1800 μg/g) impacted its discriminatory performance. The AUC for differentiating moderate from severe activity decreased to 0.841 (95% CI: 0.789–0.894). Furthermore, FC could not effectively distinguish ASUC from non-ASUC severe patients [median FC: 1800 μg/g vs. 1800 μg/g, P = 0.0638]. Conclusion This study establishes and validates a set of FC cut-off values for stratifying endoscopic activity in UC, supporting its role as a valuable non-invasive alternative to endoscopy. However, FC was not associated with disease extent, and its utility in distinguishing ASUC and precisely differentiating moderate from severe activity was limited, partly due to the assay’s upper detection limit. In these specific scenarios, integrating FC with other clinical indicators is recommended

Background Redox imbalance and systemic oxidative stress are implicated in the pathophysiology of inflammatory bowel disease (IBD). Oxidative stress previously demonstrated strong associations with endoscopic disease activity in IBD1,2. In this study, we aimed to prospectively evaluate a panel of redox proteins, including circulating total free thiols (FTs), low-molecular-weight thiols including cysteine, glutathione (GSH), and homocysteine, ischemia-modified albumin (IMA), and thioredoxin-1, as biomarkers for endoscopic disease activity in patients with IBD. Methods Patients with IBD (n = 111) undergoing surveillance endoscopy were prospectively enrolled. Blood samples were collected at endoscopy along with clinical and biochemical disease activity assessments. Endoscopic disease activity was graded using the Mayo endoscopic subscore for patients with ulcerative colitis (UC) or the Simple Endoscopic Score for Crohn’s disease (SES-CD) for patients with Crohn’s disease (CD). Serum and plasma biomarkers (FTs, GSH, IMA, homocysteine, cysteine, thioredoxin-1) were measured by ELISA. Multivariable logistic regression analysis was used to investigate associations with disease activity, while adjusting for relevant confounders including sex, age and systemic steroid usage. Results Among all biomarkers, only serum GSH remained significantly associated with active endoscopic disease in multivariable analysis (adjusted odds ratio (OR) per doubling: 4.19, p = 0.04) (Fig. 1A). This was most evident in CD (p = 0.05), but not significant in UC (p = 0.10). IMA only showed a univariable association (p < 0.05) (Fig. 1B). ROC analysis identified GSH as the most accurate oxidative stress marker in distinguishing quiescent from active endoscopic disease (AUC=0.71 in CD; 0.65 in UC) (Fig. 1C). All these biomarkers were individually outperformed by fecal calprotectin (AUC=0.77). However, combining calprotectin with these oxidative stress markers substantially improved discriminative capacity (AUC=0.95) (Fig. 1D). Conclusion Serum GSH may serve as a systemic biomarker of endoscopic disease activity in IBD, particularly in patients with CD. While less accurate than fecal calprotectin alone, systemic oxidative stress markers strongly enhance its diagnostic performance, suggesting complementary value for disease monitoring.

Data on the value of therapeutic drug monitoring of infliximab (IFX) to predict mucosal healing (MH) in inflammatory bowel diseases (IBD) are scarce. All consecutive patients with IBD receiving ongoing IFX (5 mg/kg) treatment and developing secondary failure to IFX were enrolled in a prospective study between June 2010 and May 2011. IFX trough levels, antibodies to IFX concentrations, C-reactive protein levels, and fecal calprotectin were measured before IFX optimization and at week 8. A proctosigmoidoscopy was performed on the day of first IFX optimization and at week 8 in all patients with ulcerative colitis (UC). MH was defined by fecal calprotectin <250 μg/g stools in Crohn's disease (CD) and by an endoscopic Mayo score of 0 or 1 in UC. This study included 52 patients with IBD: 34 patients with CD (mean Crohn's Disease Activity Index, 300; mean C-reactive protein, 28 ± 10 mg/L; mean fecal calprotectin, 705 ± 300 μg/g) and 18 patients with UC (mean Simple Clinical Colitis Activity Index, 7; mean Mayo endoscopic score, 3). After IFX dose intensification, half of CD and UC patients achieved MH. Increase in IFX trough levels (called "delta IFX" in micrograms per milliliter) was associated with MH in both CD and UC (P = 0.001). A delta IFX >0.5 μg/mL was associated with MH (sensitivity [se], 0.88; specificity [sp], 0.77; P = 0.0001, area under the receiver operating characteristic curve, 0.89). On multivariate analysis, the only factor associated with MH after IFX optimization was a delta IFX >0.5 µg/mL (likelihood ratio = 2.02; 95% confidence interval, 1.01-4.08; P = 0.048) in patients with IBD. Therapeutic drug monitoring of IFX strongly predicts the likelihood of achieving MH following IFX dose intensification in both CD and UC.

Faecal calprotectin assay after induction with anti-Tumour Necrosis Factor α agents in inflammatory bowel disease: Prediction of clinical response and mucosal healing at one year

Background Anaemia is the most common systemic complication of Inflammatory Bowel Disease (IBD). Contemporary studies linking its prevalence with symptom burden at disease onset are limited. We present the prevalence and disability associated with anaemia in a large new onset adult IBD cohort. Methods Demographic, clinical and biochemical indices were collected prospectively in patients referred with suspected IBD between January 2021 - April 2023. Anaemia was defined as haemoglobin (Hb) of &amp;lt;115g/L in women and &amp;lt;130g/L in men. Iron deficiency was defined as Ferritin &amp;lt;30ug/L (&amp;lt;100ug/L if active inflammation – CRP &amp;gt;5mg/L, Faecal Calprotectin [FCP] &amp;gt;200ug/g) or Iron saturations &amp;lt;15%. IBD disk scores were collected in a subgroup of patients. For two groups, non-parametric Mann-Whitney U tests were utilised, with a pairwise Dunn test and holm corrected p values for more than two. Results Hb results were available for 586 patients (182 CD, 170 UC, 234 non-IBD). Of these, an IBD disk score was available for 245 (84 CD, 71 UC, 90 non-IBD). Hb levels were significantly lower in CD than non-IBD (Table 1). Overall, a significantly larger proportion of patients with CD were anaemic than UC (X2 10.2 p=0.001, odds ratio 2.4 [95% CI 1.39-4.16]). Whilst most anaemic patients in both groups were iron deficient, many without anaemia also had demonstrable iron deficiency (Figure 1). In CD, Hb levels were significantly lower in ileocolonic disease than either isolated ileal (median Hb 125vs135.5g/L, p=0.002) or isolated colonic (125vs139g/L, p=0.002). Across IBD, Hb significantly correlated with Harvey Bradshaw Index (n=142, Spearman’s Rho [SR] -0.23 p=0.007), Partial Mayo (n=143, SR -0.23 p=0.006), Simple endoscopic score for CD (n=130, SR -0.29 p&amp;lt;0.001) and FCP (n=314, SR -0.23 p&amp;lt;0.001). Regarding overall disease burden, Hb correlated with overall disability as determined by the IBD disk (n=155, -0.23 p=0.004). Anaemic patients had higher overall disability (total disk score 62.5vs49 p=0.007). Using individual disk domains, those with anaemia had higher fatigue (median 9vs8, p=0.012), disruption of education or work (7vs4, p&amp;lt;0.001), impairment of body image (7vs4, p=0.019) and reduced sexual function (5.5vs1, p=0.004). When compared in a linear regression alongside age, body mass index, ethnicity, IBD type and baseline FCP, Hb was the second strongest predictor of overall disk score (Model fit R=0.515, BMI t=3.05 p=0.003, Hb t=-2.41 p=0.019). Conclusion Anaemia is frequently present at IBD onset, particularly in CD. Nearly half of those without anaemia have demonstrable iron deficiency. Severity of anaemia is associated with overall disease activity but influences symptom burden and disability beyond that which is attributable to mucosal inflammation alone.

Leucine-rich alpha-2 glycoprotein (LRG) is a novel biomarker for monitoring disease activity in inflammatory bowel disease (IBD). The aim of this study was to evaluate its utility in monitoring disease activity. In this retrospective study based on case records between August 2020 and July 2021 at our two centers, we examined the correlation between serum levels of LRG and C-reactive protein (CRP) with disease activity in IBD patients. Background factors related to serum LRG levels were also analyzed. Overall, 47 Crohn's disease (CD) and 123 ulcerative colitis (UC) patients were evaluated. In patients with CD, LRG and CRP levels correlated with Harvey-Bradshaw Index (HBI) and Simple Endoscopic Score for CD (SES-CD) (LRG and HBI, r = 0.397; LRG and SES-CD, r = 0.637; CRP and HBI, r = 0.253; CRP and SES-CD, r = 0.332). In patients with UC, LRG and CRP significantly correlated with the partial Mayo score (PMS) and Mayo endoscopic subscore (MES) (LRG and PMS, r = 0.3; CRP and PMS, r = 0.282; LRG and MES, r = 0.424; CRP and MES, r = 0.459). In CD patients with normal CRP, serum LRG level was significantly higher in those with mucosal inflammation than in those with mucosal healing (16.4 vs. 10.7 μg/ mL). Stenosis was associated with serum LRG levels in CD group using multiple regression analysis. Therefore, LRG is a useful biomarker for monitoring disease activity and mucosal inflammation, and indicates the status of intestinal stenosis in IBD patients.