Introduction

In accordance to Rome IV Criteria irritable bowel syndrome (IBS) is classified into four subtypes: IBS with predominant constipation (IBS-C), IBS with predominant diarrhea (IBS-D), with mixed bowel habits (IBS-M) or IBS, unsubtyped. Some authors distinguish a post-infectious subtype of IBS, in which an acute episode of infectious gastroenteritis is a trigger of the disorder. In all the other cases, mostly psycho-emotional stress is the trigger factor, with this variant being defined as stress-associated subtype of IBS.

Aims & Methods

Aim: to study the peculiarities of the formation and course of IBS in children, depending on the trigger factor. A total of 54 patients aged 6-12 years with a verified diagnosis of IBS according to Rome criteria IV have been examined. The trigger factor of the onset of IBS was established by the interrogation of patients and their parents. The levels of trait anxiety and somatization were assessed by Children's Form of the Manifest Anxiety Scale (CMAS) questionnaire and Somatoform Symptom Screening (SOMS) test respectively. The Catechol-O-methyltransferase (COMT) gene val158met polymorphism was estimated by the polymerase chain reaction. Enzyme immunoassay Ridascreen Calprotectin (R-Biopharm AG, Germany) was used for the quantitative determination of calprotectin in stool samples.

Results

We have diagnosed post-infectious subtype of IBS in 30 children. In this group we have found significantly higher concentration of fecal calprotectin (60.0 (35.6; 129.0) vs 31.2 (21.1; 58.7 µg/g)), which is consistent with pathogenesis of this subtype of IBS. On the contrary, we have discovered that psycho-emotional stress was the trigger factor of the onset of IBS in 22 patients (stress-associated subtype of IBS). Children with stress-associated IBS had higher levels of trait anxiety (25.1±5.7 vs. 18.7±6.4) and somatization (11.1 ± 4.0 vs. 8.6 ± 3.1) in comparison to patients with post-infectious subtype of the disorder. Furthermore, the analysis of the COMT gene val158met polymorphism revealed, that almost the half patients (48%) with stress-associated IBS had 472 AA (Met/Met) genotype. Met/Met carriers have genetically determined low enzymatic activity of COMT, which may lead to decreased elimination of catecholamines and is associated with chronic stress. In contrast, only 31% of children with post-infectious subtype of IBS were found to have 472 AA (Met/Met) genotype.

Conclusion

Our study suggests that not only predominant bowel habit, but also trigger factor in the development of IBS determine the heterogeneity of the disorder. This approach may be used for classification of IBS in children, as it dictates treatment strategy.

References

1. Lacy, B. E., & Patel, N. K. (2017). Rome Criteria and a Diagnostic Approach to Irritable Bowel Syndrome. Journal of clinical medicine, 6(11), 99. https://doi.org/10.3390/jcm6110099
2. Barbara, G., Cremon, C., Pallotti, F., De Giorgio, R., Stanghellini, V., & Corinaldesi, R. (2009). Postinfectious irritable bowel syndrome. Journal of pediatric gastroenterology and nutrition, 48(2), S95–S97. doi:10.1097/MPG.0b013e3181a15e2e
3. Chen, J., Lipska, B. K., Halim, N., Ma, Q. D., Matsumoto, M., Melhem, S., …& Weinberger, D. R. (2004). Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. American journal of human genetics, 75(5), 807–821. doi.org/10.1086/425589
4. Semen, M. O., Lychkovska, O. L., Tyrkus, M. Y., Kaminskyy, D. V., & Yelisyeyeva, O. P. (2023). Association between Val158Met polymorphism in the COMT gene with anxiety and heart rate variability in children with irritable bowel syndrome. Zaporozhye Medical Journal, 25(5), 439–446. https://doi.org/10.14739/2310-1210.2023.5.278878

Disclosure

Nothing to diclosure.

Introduction

We conducted a retrospective analysis of a large U.S. based administrative claims database comparing the risk of major adverse cardiovascular events (MACE) and venous thromboembolism (VTE) among patients with inflammatory bowel disease (IBD) initiating advanced biological therapies.

Aims & Methods

Patients with CD and UC who were incident users of advanced biological agents from 2013 to 2023 were identified within the Optum Labs® database. The therapeutic agents included either tumor necrosis factor-α (TNF) antagonists (infliximab, adalimumab, and certolizumab pegol), IL-12/23 antagonists (ustekinumab), IL-23 antagonists (risankizumab), anti-integrin agents (vedolizumab), Janus kinase (JAK) inhibitors (tofacitinib and upadacitinib), or S1PR modulators (ozanimod). Eligible patients were required to have continuous insurance coverage for at least one year before and after treatment initiation. We estimated incidence rates (IRs) and compared risks for VTE and MACE (myocardial infarction and stroke). Fatal cardiovascular outcomes were excluded due to limited specificity and data constraints.
To account for baseline confounding, we applied stabilized inverse probability of treatment weighting (IPTW) using multinomial propensity scores. Hazard ratios were estimated using Cox proportional hazard models.

Results

We included 12,245 patients with CD (mean age: 44.5 ± 17.5 years; 54.2% female; 30.9% using concomitant steroids), and 9,430 patients with UC (mean age: 47.5 ± 17.7 years; 49.2% female; 50% on concomitant corticosteroids). Patients receiving JAK inhibitors and vedolizumab were more likely to have higher comorbidity burden than others for CD while those receiving IL-23 antagonists had the most comorbid burden for UC patients, when assessed through proportion of patients with Charlson comorbidity index of ≥ 5. In UC patients, VTE incidence rates ranged from 1.69 to 2.01 for VTE and MACE rates from 0.52 to 0.99 per 100 person-years. For CD, VTE incidence rates ranged from 0.89 to 2.33 and for MACE, 0.68 to 1.73. Hazard ratios comparing the risk of events across therapies is presented in table 1.

Table 1: Hazard ratios for risk of VTE and MACE in patients with Crohn’s disease and Ulcerative colitis receiving advanced biological therapies and small molecules

Conclusion

In this large real-world IBD cohort, there was no difference in risk of adverse cardiovascular and thrombotic events between any biological agent or small molecule, in compairosn to TNF antagnoists.

Disclosure

• CM: Consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Forte Biosciences, Fresenius Kabi, Gilead, Janssen, McKesson, Mirador Therapeutics, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda, Tillotts Pharma; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Eli Lilly, Ferring, Fresenius Kabi, Janssen, Merck, Organon, Pendopharm, Pfizer, Sanofi, Takeda, Tillotts Pharma; royalties from Springer Publishing; research support from AbbVie, Eli Lilly, Ferring, Pfizer.
• VJ: Consulting/advisory board fees from AbbVie, Alimentiv Inc, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma, Roche, Sandoz, Second Genome,Takeda, Teva, Topivert, Ventyx, Vividion; speaker’s fees from, Abbvie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda, Fresenius Kabi
• SS: Research grants from Pfizer

Introduction

Pancreatic exocrine insufficiency (PEI) is characterized by a significant reduction in pancreatic exocrine activity within the intestine, impairing normal digestive processes ⁽¹⁾. This condition results in malnutrition-related complications and a diminished quality of life. Faecal pancreatic elastase serves as an optimal biomarker for evaluating pancreatic function in individuals with PEI. Its high stability ensures that faecal pancreatic elastase is concentrated during intestinal transit, thereby accurately reflecting total pancreatic secretion. The BÜHLMANN fPELA^® turbo is a particle-enhanced turbidimetric immunoassay (PETIA) that is commercially available for the automated quantification of pancreatic elastase in faecal extracts using clinical chemistry analyzers. Additionally, BÜHLMANN has developed the Quantum Blue^® fPELA, a lateral flow immunoassay (LFIA) designed for environments requiring lower sample volumes. This study aimed to evaluate the clinical performance of both assays and compare them to a commercially available ELISA reference method.

Aims & Methods

A total of 189 symptomatic patients, comprising 82 non-PEI controls and 107 PEI-diagnosed patients, were utilized to compare the clinical performance of PETIA and LFIA against the ELISA reference assay. Sensitivity and specificity for both assays were determined using cutoffs of 100 μg/g and 200 μg/g.

Results

The area under the curve (AUC) was 0.809 for the BÜHLMANN fPELA^® turbo (optimal cut-off: 166 μg/g), 0.792 for the Quantum Blue^® fPELA (optimal cut-off: 109 μg/g), and 0.814 for the reference ELISA (optimal cut-off: 154 μg/g). At clinically relevant cut-offs of 100 μg/g and 200 μg/g, the BÜHLMANN fPELA^® turbo demonstrated sensitivity of 0.57 and 0.74, and specificity of 0.9 and 0.76, respectively. The Quantum Blue^® fPELA showed sensitivity of 0.62 and 0.71, and specificity of 0.93 and 0.74, respectively. The reference ELISA exhibited sensitivity of 0.64 and 0.73, and specificity of 0.87 and 0.70, respectively. A direct method comparison using at least 60 samples within the linear measuring range of all assays revealed a relative median difference in Bland-Altman analysis of 9.3% between the BÜHLMANN fPELA^® turbo and the reference ELISA, 10.8% between the ELISA and the Quantum Blue^® fPELA, and 11.0% between the PETIA and the LFIA.

Conclusion

The study demonstrated that both the BÜHLMANN fPELA^® turbo and the Quantum Blue^® fPELA exhibit strong diagnostic performance to detect PEI in symptomatic patient population and high concordance with the reference ELISA assay. The BÜHLMANN fPELA^® turbo, a particle-enhanced turbidimetric immunoassay, is an accurate, non-invasive, automated test ideal for large-scale determination of pancreatic elastase levels in faecal extracts. Meanwhile, the Quantum Blue^® fPELA rapid test is well-suited for smaller laboratories, offering a faster time to result compared to traditional ELISA methods, while offering a coequal clinical performance.

References

(1) Philips ME, et al. BMJ Open Gastro 2021; 8: e000643

Disclosure

Conflict of interest: CR, DT, HI, AT, MU, RT, MS, TS, SN and CG are employees of BÜHLMANN Laboratories AG

Introduction

Tofacitinib and upadacitinib are Janus kinase (JAK) inhibitors that are increasingly used for the treatment of acute severe ulcerative colitis (ASUC). However, comparative analyses of safety and effectiveness have not been performed for their use in this setting.

Aims & Methods

This multicenter, retrospective study enrolled hospitalized adult patients treated with tofacitinib or upadacitinib for ASUC between January 2019 and June 2024. The main outcomes were clinical response, clinical remission, and colectomy-free survival. Propensity-adjusted analyses using inverse probability treatment weighting (IPTW), and double robust estimations (DRE) were used to control for confounding factors.

Results

In total, 111 patients (60 tofacitinib, 51 upadacitinib) were enrolled across 23 international centers. JAK inhibitors were used to induce response in 86 (77%) patients and used to maintain response after adequate intravenous steroid response in 25 (23%). The median follow up was 31 weeks (IQR 13-64). Between days 3-7 after treatment initiation, upadacitinib was associated with greater response rates 84% vs. 54%, p=0.02, but response/remission were comparable at day 98 (45%/36% vs 55/48%) and day 182 (29/29% vs. 39/34%). Sub-analyses for JAK inhibitor use as salvage therapy (tofacitinib (n=35) vs. upadacitinib (n=31)) showed similar effectiveness outcomes across both groups. The probabilities of colectomy-free survival at days 98/182 for tofacitinib and upadacitinib were 79%/75% and 80%/78%, respectively, with no significant differences in the comparison of survival curves, p=0.99. Treatment failure rates (where JAK inhibitor was used to maintain remission) were similar at days 98 and 182. The frequency of adverse events was comparable.

Conclusion

This is the first comparative study of JAK inhibitors in ASUC and presents the largest series of JAK inhibitor-treated patients to date. Tofacitinib and upadacitinib appear to have similar effectiveness for inducing remission and preventing colectomy with comparable safety outcomes. Further prospective studies with longer-term follow up are needed to validate these findings.

Disclosure

No conflicts of interest for this study. No funding received.

Introduction

Current guidelines provided information on the management of patients with gastrointestinal bleeding, in particular focusing on admission, endoscopic management and medical treatment during the hospital stay. So far, 11-15% of patients treated for GIB required a new hospitalization for a new bleeding episode.

Aims & Methods

The aim of the study is to verify if the management in a dedicated practice after hospital discharge for gastrointestinal bleeding reduces further bleeding and costs. This is an ambispective cohort single center study, including patients observed between May 2022 and September 2023 in our clinical practice dedicated to gastrointestinal bleeding. We enrolled consecutive patients with overt gastrointestinal bleeding or iron deficiency anemia affected by vascular lesions. The effectiveness was defined as a composite endpoint including iron supplementation, blood transfusion, medical treatment and number of hospital stay. Costs were evaluated starting from Diagnosis Related Groups (DRG) codes. The cost effectiveness analysis and ICER has been calculated using the ICERconf.EXE software (Software Prescriptions, c/o Bob Obenchain, California, USA).

Results

In our institute 602 patients with gastrointestinal bleeding were evaluated between May 2022 and September 2023, of these 79 were included in the study. The mean age was 73.8 years (SD±10,8), 46% were female. The source of bleeding was angiodysplasia in 63% of patients, GAVE in 9% (Gastric Antral Vascular Ectasia), erosions in 9%. After the introduction in the dedicated practice, the re-bleeding decrease from 1.3 episodes to 0.2 episodes, p<0.001. The cost average after the practice was 4074 euro (SD ±5485), the average cost before the practice was 4885 euro (SD ±4567), it has been observed a cost saving after the management in the dedicated practice, C diff= -751 euro. The average effectiveness after practice was 8.7 (SD±1.06) and the average effectiveness before the practice was 7.3 (SD ±1.3) with the E diff= 1.47, p<0.001.

Conclusion

The dedicated practice for patients with gastrointestinal bleeding provides effectiveness in reducing transfusion, iron supplementation and hospitalization with a consistent cost reduction.