Introduction

Ulcerative colitis (UC) is a progressive disease and associated with reduced quality of life.¹ Treatment goals for patients with UC are to induce and maintain clinical remission, and avoid or delay the need for surgery.^2,3 Increasing number of advanced treatment options have been approved in recent years for patients with UC. However, the optimal treatment pathway is not well understood. Guselkumab, a dual-acting IL-23 inhibitor, has demonstrated clinical remission as high as 50.0% at maintenance Week 44 in the Phase 3 QUASAR study, suggesting the potential of guselkumab to provide durable clinical remission.⁴ A disease model was developed to identify the optimal treatment sequence with guselkumab for patients with moderate-to-severe UC.

Aims & Methods

A hybrid decision tree/Markov disease model was developed to project rates of clinical remission, response and active disease for patients with UC over five years. Patients were first distributed into health states representing remission, response without remission, and active UC (no response) based on the rates of clinical remission and response reported in the induction phases of Phase 2 and Phase 3 trials. Over time, loss of response and transition to the next line of therapy is derived based on loss of response rates in the trial data. Up to three treatment lines were modelled, and patients who lose response after third-line treatment are categorized as in active disease state where they can receive surgery. Age- and sex-adjusted mortality rates obtained from the US population life table were applied in the model. Three treatment sequences were assessed, where guselkumab was placed in first-line, second-line, and third-line, respectively. A treatment basket was used for the other lines of therapy, informed by 2024 market share data from MarketScan. We report the predicted average proportion of time spent in each health state for each of the three treatment sequences over five years.

Results

Over a 5-year period, the predicted average proportion of time patients spent in active disease is consistently lower for patients treated with guselkumab as a first-line therapy compared to those receiving it in later lines. In the first year, patients receiving first-line guselkumab spent 28% of time in active disease, while those treated with guselkumab in the second or third line spent 33%. This difference becomes more pronounced over the 5-year period, with proportion of time in active disease at 36% for first-line guselkumab use versus 48% and 51% for second- and third-line use, respectively. The reduction in time in active disease with earlier use of guselkumab infers that patients are asymptomatic, as patients are also projected to experience longer time in remission. The model predicts that, over 5 years, patients treated with first-line guselkumab spend an average of 52% of their time in remission, in contrast to 40% and 38% for those treated with guselkumab in the second- or third-line, respectively.

Table 1: Projected average proportion of time spent in each health state over a 5-year period

	Remission	Response without remission	Active UC	Surgery
First-line guselkumab	52.1%	10.8%	36.4%	0.7%
Second-line guselkumab	39.5%	11.9%	47.7%	0.9%
Third-line guselkumab	38.1%	9.9%	51.0%	1.0%

Conclusion

Model projections suggest that using guselkumab in first line is associated with long-term sustained remission for patients with UC, compared to using guselkumab in later lines of treatment.

References

1. Armuzzi A, Liguori G. Quality of life in patients with moderate to severe ulcerative colitis and the impact of treatment: A narrative review. Dig Liver Dis. 2021;53(7):803-808.
2. Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG Clinical Guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019;114(3):384-413.
3. Feuerstein JD, Isaacs KL, Schneider Y, et al. AGA clinical practice guidelines on the management of moderate to severe ulcerative colitis. Gastroenterology. 2020;158(5):1450-61.
4. Rubin DT, Allegretti JR, Panes J, et al. Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies. Lancet. 2025;405(10472):33-49.

Disclosure

Mariya Dimova, Mi Jun Keng, Dominik Naessens, Sumesh Kachroo, Shashi Adsul, Mario Gomez, and Elise Wu are employees of and may hold stock/stock options in Johnson & Johnson.

Clinical Case Summary

Aims: We report 3 cases of new inflammatory bowel disease (IBD) which occurred in multiple sclerosis (MS) patients undergoing ocrelizumab therapy over last year in Irish Teaching Hospital setting.
Background: Ocrelizumab, a monoclonal antibody targeting CD20-positive B cells, is an established treatment for MS. While it is generally well-tolerated, emerging reports suggest a possible link to gastrointestinal complications, including IBD.
Methods: Three MS patients presented after starting ocrelizumab with gastrointestinal symptoms suggestive of inflammatory bowel disease. They were fast-tracked for endoscopic evaluation by an experienced gastroenterologist specializing in IBD. Diagnosis was based on clinical presentation, endoscopic findings, and histological analysis. Data regarding symptom onset, disease severity, colitis grade, inflammation distribution, and treatment response were assessed.
Results: A temporal relationship was observed between ocrelizumab initiation and IBD onset in all three cases, with symptoms emerging after 4-6 infusions. Reported symptoms included diarrhoea, nausea, urgency, and abdominal pain. Faecal calprotectin levels at time of referral ranged from 900 to 1800 µg/g. Endoscopy confirmed mild colitis and terminal ileitis, while histology revealed active colitis with cryptitis, acute terminal ileitis, or normal colon findings. Treatment with steroids, Mesalazine, and antibiotics led to symptom resolution in all cases. Discontinuing ocrelizumab resulted in recovery within 4-6 weeks, with no relapse over an average follow-up of two months.
Conclusion: These cases suggest a potential association between ocrelizumab and IBD onset or exacerbation in MS patients. Symptom resolution upon drug withdrawal supports a possible causal relationship. Clinicians should be aware of this risk to facilitate early detection, management, and patient education.

References

https://journals.lww.com/acgcr/Fulltext/2022/01000/Severe_Ocrelizumab_Induced_Enterocolitis_Treated.31.aspx
https://pubmed.ncbi.nlm.nih.gov/32198886/

Disclosure

No Conflict of Interest

Clinical Case Summary

We report a case of Intrahepatic Cholestasis of Pregnancy (ICP) leading to a rejections of a living, related donor liver two years after the liver transplantation (LT). The 36yo patient underwent LT in November 2021 in Mongolia due to a HBV/HDV related liver cirrhosis. Until August 2024, she had normal test results when she presented with severe pruritus and jaundice at 16-17th week of her second pregnancy. The ICP was diagnosed after elevated total bile acids were detected. A medical pregnancy termination was induced with subsequent three sessions of plasmapheresis. The patient's condition deteriorated further before she received her second living, unrelated donor LT in December 2024.
.

	2023.07.03- prior to pregnancy	2024.08.18- during the pregnancy	2024.09.30- A month after termination	2024.11.04	2025.02.02- Two months after re-transplantation
Total bilirubin (mg/dL) /norm 0-1.2/	1.5 N	17.6 H	20.2 H	40.6 H	0.73 N
GOT/GPT (IU/mL) /norm 0-40/	11.3/18.3 N	265.3/196.1 H	79.5/77.1 H	262.5/113.1 H	6.2/7.6 N
Total bile acids (umol/mL) /norm 0-10/		170.2 H	332 H		7 N

The explant histology stated a massive hepatocellular necrosis (fulminant), total bile duct loss, massive cholestasis (canalicular and intracellular), allograft arteriopathy: Foamy histiocytes in the intimal artery, Arteriosclerosis and Lumen narrowing. No genetic test was performed , either prior or after the LTs. The final diagnosis: An Intrahepatic Cholestasis of Pregnancy leading to a liver graft rejection.
The ICP is a relatively common pregnancy related condition (0.2-2% of pregnancies in Europe and Americas¹) that presents with jaundice and pruritus. The condition usually improves after delivery/termination. In rare cases elevated serum bile acid levels lead to fetal abnormalities or loss of pregnancy. Since the patients condition did not improve after the pregnancy termination in September, 2024, Progressive Familial Intrahepatic Cholestasis (PFIC) was suspected when she admitted her first pregnancy was also complicated by ICP. Better history taking is needed to prevent graft rejection due to bile acid transport dysfunction.

References

1- Williamson, C. and V. Geenes, Intrahepatic cholestasis of pregnancy. Obstet Gynecol, 2014. 124(1): p. 120-133

Clinical Case Summary

MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) is a rare mitochondrial disorder characterized by multisystem involvement, particularly in the neurological, cardiovascular, and gastrointestinal (GI) systems. GI manifestations are less commonly discussed but can present significant clinical challenges, including dysmotility, bowel ischemia, and obstruction.
A 19-year-old male, with a family history of MELAS affecting multiple relatives, was admitted with status epilepticus and other associated neurological and cardiovascular symptoms. On admission, the patient exhibited severe metabolic acidosis and elevated lactate levels, raising suspicion for mitochondrial dysfunction. During his ICU stay, he was found to have significant GI symptoms, including a post-operative ileus likely secondary to dysmotility syndrome associated with MELAS. He was subsequently diagnosed with a faecal bezoar causing large bowel obstruction (LBO) in the sigmoid colon, requiring laparotomy with disimpaction of the faecal mass, and decompression of the small and large bowel. There was evidence of bowel ischemia during the surgical exploration, with friable mucosa and necrotic areas observed in the proximal rectum and descending colon. Fortunately, all bowel sections were viable after decompression, and no further ischemic damage was noted.
This case highlights the importance of considering gastrointestinal complications, such as fecal bezoars and bowel ischemia, in patients with MELAS syndrome. GI manifestations, though less commonly recognized, can lead to significant clinical issues such as bowel obstruction and ischemic damage. Early intervention, including surgical management and decompression, is crucial to preventing further complications. Awareness of these potential issues is essential for clinicians managing patients with MELAS, as prompt treatment can improve outcomes and mitigate the risk of severe long-term GI dysfunction.

References

1. Colonoscopy images of diffuse friable mucosa with necrosis in sigmod colon and descending colon

Introduction

Aims & Methods

The purpose of this study is to evaluate the feasibility of extracting RNA in sufficient quantity and quality to perform genomic analyses from specimens obtained through EUS-fine needle aspiration (EUS-FNA) of PanNENs, comparing three methods of RNA preservation and extraction.

Results

Conclusion

Introduction

The consequences of chronic pancreatitis (CP) may not be exclusively limited to the pancreas or restricted to the gastrointestinal tract but could also be systemic. To date, the relationship between chronic pancreatitis and cardiovascular risk factors has not been studied extensively. We conducted a systematic review and meta-analysis to examine if the combination of chronic inflammatory changes may possibly place CP patients at risk for cardiovascular disease.

Aims & Methods

We systematically searched PubMed, Scopus, and Cochrane Register of Controlled Trials for observational studies that compared major cardiovascular outcomes in patients with chronic pancreatitis. The outcomes explored were: (1) acute coronary disease/myocardial infarction; (2) hypertension; (3) hyperlipidemia; and (4) diabetes mellitus. We computed odds ratio (OR) for binary endpoints, with 95% confidence intervals (CI). Heterogeneity was examined I² statistics; p values less than 0.10 and I² > 25% were considered significant for heterogeneity.

Results

Four observational studies comprising a total of 57,721 patients with chronic pancreatitis were included in this meta-analysis. The most consistent finding across studies was a significantly higher risk of diabetes mellitus in patients with chronic pancreatitis compared to a control group without chronic pancreatitis (OR 4.77; 95% CI 1.32–17.28; p=0.017; I²=100%). In contrast, no statistically significant associations were found between chronic pancreatitis and other cardiovascular outcomes, including cerebrovascular disease (OR 1.59; 95% CI 0.98–2.57; p=0.05; I²=99.4%), acute coronary syndrome/myocardial infarction (OR 1.35; 95% CI 1.00–1.82; p=0.049; I²=95.4%), hypertension (OR 0.52; 95% CI 0.30–7.61; p=0.608; I²=99.9%) or hyperlipidemia (OR 2.60; 95% CI 0.36–18.77; p=0.342; I²=100%).

Conclusion

The results of our meta-analysis suggest that chronic pancreatitis is not associated with increased risk of cardiovascular disease despite being associated with a higher risk of diabetes mellitus.

Introduction

Pancreatic neuroendocrine tumors (NETs) are rare neoplasms that are classified as functional (F-NET) or nonfunctional (NF-NET) depending on the presence or absence of excess hormone production. Endoscopic Ultrasound guided fine needle aspiration (EU-FNA) is often used to diagnose NETs but there are limited data on its sensitivity for this purpose.

Aims & Methods

To determine the sensitivity of EUS-FNA for the diagnosis of a NET.
A prospective randomized trial study, from May 2013 to Abril 2025 was performed in a referred Gastrointestinal hospital in Brazil. A total of 184 patients underwent EUS for suspected NETS and collected materials from fine needle aspiration and sent to histopathology analyzes. The diagnosis of a NET was confirmed by: 1) EUS-FNA with or without confirmatory immune chemistry (ICC) with synaptophysin and chromogranin form pancreatic mass or metastatic site; or 2) an alternative biopsy method and/or surgical resection of the pancreas or other metastatic site

Results

184 patients (112 male; median age: 54 yrs, range: 21-78 yrs) with 68 (37%) F-NETs and 116 (63%) NF-NETs were identified. By EUS, the tumors were located in the pancreas head, body, tail or were multifocal in 76 (41%), 54 (29%), 38 (21%) and 16 (18%), respectively. Of these 184, 152 (83%) underwent EUS-FNA of a pancreatic mass, 72 (47%) of whom also had a EUS-FNA of an alternative (nonpancreatic) site including liver (n=30; 16%), another lesion in the pancreas (n=14; 8%), or lymph node (n=18; 10% peripancreatic in 10, celiac in 6 and mediastinal in 2). Immunohistochemistry was performed in 102/152 (67%) EUS-FNA specimens and the result were: ICC-positive (n=88), ICC-negative (n=10), not interpretable (n=2) or inadequate for interpretation (n=2), Surgery was performed in 82 (54%): distal pancreatectomy (n=32), Whipple procedure (n=20), enucleation (n=20) and subtotal (n=4) and total pancreatectomy (n=2). The remaining four who underwent surgery had an exploration laparotomy only. 132 patients had a confirmed diagnosis of NET and the sensitivity of EUS-FNA was respectively: all patients 84%, F-NET 78%, NF-NET (89%) and lesions less than or equal to 13 mm (62%). The results of the false-negative EUS-FNA biopsies of pancreas (n=24) were interpreted as: normal in 4; suspicious in 4, nondiagnostic in 10, adenocarcinoma in 4, and a solid pseudopapillary tumor in 2.

Conclusion

EUS-FNA is a sensitive method for the diagnosis of pancreatic NETS but yield is lower in tumor smaller than 13mm in diameter.