Introduction

Long-term data on bowel urgency (BU) in Crohn’s disease (CD) are limited, and the associations with other efficacy outcomes are not well studied.

Aims & Methods

Our aims were to examine the long-term efficacy of mirikizumab (MIRI) on BU remission and the associations between BU remission and clinical remission, endoscopic remission, and patient-reported outcomes (PRO) improvement at week (W) 104 in patients with moderately to severely active CD who were randomized to MIRI in the Phase 3 study VIVID-1 and continued into the long-term extension study VIVID-2. In VIVID-1, the MIRI group received induction with 900 mg intravenously (IV) at W0, W4, and W8, then 300 mg subcutaneously (SC) every 4W. W52 endoscopic responders (≥50% reduction from baseline in Simple Endoscopic Score for CD [SES-CD]) continued MIRI SC dosing in VIVID-2. Endoscopic non-responders received reinduction with MIRI IV (3x Q4W) at the start of VIVID-2 followed by SC dosing (IV-SC) as described. Patients that had an Urgency Numeric Rating Scale (UNRS) ≥3 (least to worst range 0-10) at baseline were included in these analyses. BU remission was defined as an UNRS score of ≤2. Associations between BU remission with clinical remission by Crohn’s Disease Activity Index (CDAI), endoscopic remission, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (range 0-52, higher is better), and Inflammatory Bowel Disease Questionnaire (IBDQ) remission, were assessed at W104, within the VIVID-1 W52 endoscopic response subgroups as well as the MIRI total group. Discontinuations or missing data were handled using modified non-responder imputation (mNRI) for categorical data. Missing values were imputed by multiple imputation and modified baseline observation carried forward for FACIT-Fatigue change from baseline.

Results

Over 50% of the MIRI total group, 56% of MIRI W52 endoscopic responders, and 43% of the MIRI W52 endoscopic non-responders achieved BU remission at W104. In the MIRI total group, a significantly higher percentage of patients achieved clinical remission, endoscopic remission and IBDQ remission at W104 in the BU remission group compared to those without BU remission. The improvement in fatigue by FACIT-Fatigue score was significantly more in the group with BU remission versus those without BU remission (p<0.0001). In both MIRI W52 endoscopic responders and non-responders, patients who achieved BU remission at W104, compared to those who did not, achieved significantly higher rates of clinical remission, greater improvements in FACIT-Fatigue, and higher rates of quality of life improvement measured by IBDQ remission (Table 1).

Table 1

Endpoint at W104	MIRI Total N=405			MIRI W52 endoscopic responders N=236			MIRI W52 endoscopic non-responders N=169
	With BU Remission (51%)	Without BU Remission (49%)	p-value	With BU Remission (56%)	Without BU Remission (44%)	p-value	With BU Remission (43%)	Without BU Remission (57%)	p-value
Clinical remission by CDAI, %	96%	48%	<0.0001	98%	54%	<0.0001	93%	41%	<0.0001
Endoscopic remission, %	34%	21%	0.018	49%	35%	0.058	10%	5%	0.219
FACIT-Fatigue CFBL, mean (SD)	12.2 (1.0)	5.9 (0.9)	<0.0001	12.3 (1.2)	6.1 (1.3)	0.001	12.2 (1.5)	5.7 (1.2)	0.002
IBDQ remission, %	87%	43%	<0.0001	89%	45%	<0.0001	82%	40%	<0.0001
Footnote: P-values for all binary outcomes are from CMH test adjusted by biologic-failed status (yes/no), baseline SES-CD total scores (<12, ≥12), either baseline SF ≥7 and/or baseline AP ≥2.5 (yes or unknown/no). P-values for FACIT-Fatigue are from t-test. mNRI was applied to all binary outcomes and BU remission. Multiple Imputation was applied to FACIT-Fatigue after mBOCF was applied. IBDQ remission is based on patients with baseline IBDQ<170. Clinical remission by CDAI is defined as CDAI total score <150. Endoscopic remission is defined as SES-CD ≤4 and ≥2-point reduction from baseline, and no subscore >1. Abbreviations: AP= abdominal pain; BU= bowel urgency; CDAI= Crohn’s disease activity index; CI=confidence interval; CFBL = change from baseline; CMH= Cochran Mantel Haenszel; mBOCF= Modified Baseline Observation Carried Forward; MIRI = mirikizumab; mNRI = modified nonresponder imputation; N = number of patients in the analysis population; FACIT= Functional Assessment of Chronic Illness Therapy; IBDQ = Inflammatory Bowel Disease Questionnaire; SD= standard deviation; SES-CD = Simple Endoscopic Score for Crohn’s Disease; SF= stool frequency; W=week

Conclusion

Over 50% of patients with CD achieved BU remission at 2 years of treatment with MIRI. These results highlight that the achievement of BU remission corresponded with improvements to outcomes important to patients with CD, underscoring the importance of long-term management of BU in improving overall patient outcomes.

Disclosure

SRV: has received consulting fees, speaker’s honoraria and unrestricted research grants from Abbott, Alfasigma, Amgen, Arenapharm, BMS, Falk Pharma GmbH, Ferring Pharmaceuticals, Gilead, iQuone, Janssen, MSD, Permamed, Pfizer, Sanofi-Aventis, Schwabe Pharma, Takeda, Tillotts, UCB and Vifor
DTR: receives grants or contracts from Takeda, and discloses consultancy fees with AbbVie, Altrubio, Apex, Avalo Therapeutics, Bristol Myers Squibb, Buhlmann Diagnostics Corp, Celgene, Connect BioPharma, Intouch Group, Iterative Health, Janssen Pharmaceuticals, Lilly, Pfizer, Samsung Neurologica, and Takeda. He serves on the Board of Directors for Cornerstones Health.
JW, GY, AV, REM, and RRH: Employees and stockholders of Eli Lilly.
GD-H: Has received research grants from: Alimentiv BV, Bristol Myers Squibb, Eli Lilly and Company, Pfizer, and Takeda; and consulting fees from: AbbVie, Alimentiv, AstraZeneca, Bristol Myers Squibb, Celltrion, Eli Lilly and Company, GSK, Merck Sharp & Dohme, Pfizer, Sorriso Pharmaceuticals, Takeda, Tillotts Pharma AG, and Ventyx Biosciences
ST: has received grants from: AbbVie, BUHLMANN Diagnostics, ECCO, Eli Lilly and Company, Ferring Pharmaceuticals, International Organization for the Study of Inflammatory Bowel Disease, Janssen, Merck Sharp & Dohme, Norman Collison Foundation, Pfizer, Procter & Gamble, Schering-Plough, Takeda, UCB Pharma, Vifor Pharma, and Warner Chilcott; and reports other disclosures from: Abacus Pharma, AbbVie, Actial Farmaceutica, ai4gi, Alcimed, Allergan, Amgen, Aptel, Arena Pharmaceuticals, Asahi Kasei Pharma, Aspen Pharmacare, Astellas, AstraZeneca, Atlantic Pharmaceuticals, Barco, Biocare Medical, Biogen, BL Pharma, Boehringer Ingelheim, Bristol Myers Squibb, BUHLMANN Diagnostics, Calcico Therapeutics, Celgene, Cellerix, Cerimon Pharmaceuticals, ChemoCentryx, Chiesi, Cisbio, Comcast, Coronado Biosciences, Cosmo Pharmaceuticals, Dr. Falk Pharma, Ducentis BioTherapeutics, Dynavax Technologies, Elan Pharma, Eli Lilly and Company, Enterome, Equillium, Ferring Pharmaceuticals, Galapagos NV, Genentech/Roche, Genzyme, Gilead Sciences, GlaxoSmithKline, Glenmark Pharmaceuticals, Grünenthal, GW Pharmaceuticals, Immunocore, Indigo Biosciences, Janssen, Lexicon Pharmaceuticals, Medarex, MedTrix, Merck, Merrimack Pharmaceuticals, Mestag Therapeutics, Millennium Pharmaceuticals, Neovacs, Novartis, Novo Nordisk, NPS Pharmaceuticals/Nycomed, Ocera Therapeutics, OPTIMA Pharma, Origin Pharma, Otsuka, Palau Pharma, Pentax Medical, Pfizer, PharmaVentures, Phesi, Phillips Pharma Group, Procter & Gamble, Pronota, Proximagen, Resolute Pharma, Robarts Clinical Trials, Sandoz, Santarus, Satisfai Health, Sensyne Health, Shire, Sigmoid Pharma, Sorriso Pharmaceuticals, Souffinez, SynDermix, Synthon, Takeda, Theravance Biopharma, TiGenix, Tillotts Pharma AG, Topivert, Trino Therapeutics with Wellcome Trust, TxCell SA, UCB Pharma, Vertex Pharma, VHsquared, Vifor Pharma, Warner Chilcott, and Zeria Pharmaceutical
AW: reports consulting and/or speaking fees from Abbvie, Bristol-Myers Squibb, Ferring, Galapagos, Janssen, Pfizer, and Takeda.

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

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

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

Introduction

Gallstone disease affects approximately 6% of the global population. Adequate knowledge about gallstone disease among the public can facilitate early medical consultation and enable them to navigate healthcare pathways effectively. In the digital age, patients increasingly turn to the internet for health-related information, with over half of the global population relying on it for access to knowledge.

Aims & Methods

This study aimed to evaluate the quality, readability, usability, and reliability of patient-oriented websites providing information on gallstone disease, using validated assessment tools. The three most widely used search engines, Google, Yahoo, and Bing were searched employing keywords related to gallstone disease. The first 50 search results per keyword per engine were screened. Applying the inclusion and exclusion criteria, 52 websites were selected for detailed analysis. The information was assessed for readability using the Flesch Reading Ease Score (FRES), for usability and reliability using the LIDA tool, and for overall quality using the DISCERN instrument. Statistical analysis was performed using SPSS (v27), with significance set at p < 0.05.

Results

Among the 52 websites analyzed, only sixteen (30.8%) sites had obtained Health on the Net (HON) code certification. The median FRES score of the included websites was 60.5 out of 100 (range: 33-79.6), indicating readability appropriate for readers aged 13–15 years. The median LIDA usability and reliability scores were 40 out of 54 (range: 31–54) and 24.5 out of 51 (range: 10–51), respectively. The median DISCERN score was 69.8 out of 80 (range: 30-80) with 5.8% (n=3) of websites scoring below 50%. A low DISCERN score (≤ 50%) was found in three (5.8%) websites. The DISCERN score was found to be significantly associated with LIDA reliability and LIDA overall scores (p < 0.001), government run websites (p= 0.028) and HON code certification (p = 0.01). However, no significant association was found between DISCERN scores and LIDA usability or FRES. Most websites (86.5%) provided accurate clinical information, but only 76.9% discussed treatment complications.

Conclusion

The quality of online patient information on gallstone disease varied considerably, with only a minority meeting optimal standards for readability and certification. While clinical accuracy was generally satisfactory, gaps remain in presenting treatment risks and maintaining content currency. These findings emphasize the need for improved oversight and standardization of online health content to support patient education and informed decision-making.

References

1. Internet World Stats. Internet world stats: Usage and population statistics, http://www.internetworldstats.com/stats.htm (2013, accessed 16 June 2023).
2. Lee JS, Seo HS, Hong TH. YouTube as a source of patient information on gallstone disease. World J Gastroenterol 2014; 20: 4066–4070.
3. Raptis DA, Sinanyan M, Ghani S, et al. Quality assessment of patient information on the management of gallstone disease in the internet. HPB 2019; 21: 1632–1640.
4. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the prevention, diagnosis and treatment of gallstones. J Hepatol 2016; 65: 146–181.

Disclosure

There is no conflict of interest

Introduction

Diabetes mellitus (DM) is a risk factor of pancreatic cancer (PC), but the effect of glycemic control on PC development among patients with long-standing type 2 diabetes (T2D) is not well investigated.

Aims & Methods

We aimed to investigate the benefit effect of optimal glycemic control on PC development in patients with long-standing T2D. In this retrospective cohort study, adults with newly diagnosed T2D between 2001 and 2015 were identified from a territory-wide electronic healthcare database. T2D diagnosis was based on the American Diabetes Association criteria, ICD-9 codes, or use of anti-diabetic medications. Exclusion criteria were prior history of PC, immunoglobulin G4 disease, pancreatectomy and PC cases occurring within three years of T2D diagnosis (to address reverse causality). The primary outcome was PC, while secondary outcome was PC-related mortality. For primary exposure, optimal glycemic control was defined as time-weighted mean hemoglobin A1c (HbA1c) <7%, For secondary exposure, optimal glycemic control was defined as fasting glucose (FG) ≤7mmol/L. Adjusted hazard ratios (aHRs) were derived from propensity score (PS) regression adjustment for 28 covariates including age, sex, smoking, alcohol use, body mass index, diabetes complications, history of pancreatitis and cholangitis, comorbidities, and medications (aspirin, statins, anti-diabetic drugs).

Results

Among 458,331 T2D patients (mean age:60.0±12.1 years; 51.2% male), there were 257,659 and 200,672 patients with optimal and suboptimal glycemic control. Among them, 1,382 (0.3%) developed PC and 922 (0.2%) died from PC over a mean follow-up of 10.8±4.1 years. Optimal glycemic control was associated with lower PC risk – HbA1c <7% (aHR:0.43; 95%CI:0.37-0.48) and FG <7mmol/L (aHR:0.71; 95%CI:0.63-0.80). Optimal control of both HbA1c and FG conferred lowest PC risk (aHR:0.39; 95% CI:0.33-0.46). Optimal control was also associated with lower PC-related mortality – HbA1c <7% (aHR:0.35; 95%CI:0.30-0.41) and FG <7mmol/L (aHR:0.69; 95%CI:0.59-0.79). Every 1% rise in HbA1c and 1mmol/L rise in FG was associated with higher PC risk by 46% (95%:39-35%) and 14% (95% CI:11-17%), respectively. When compared with HbA1c <7.0%, higher HbA1c conferred stepwise increase in PC risk (P_trend<0.001), with aHRs being 1.85 (95% CI:1.59-2.16), 2.52 (95% CI:2.10-3.02), 3.47 (95%CI:2.81-4.29), 3.58 (95% CI:2.76-4.66) and 4.61 (95% CI:3.72-5.70) for HbA1c levels of <7%, 7.0 to <7.5%, 7.5 to <8.0%, 8.0 to <8.5%, 8.5 to <9.0% and ≥9.0%, respectively. When compared with FG <7.0%, higher FG also conferred stepwise increase in PC risk (P_trend<0.001), with aHRs being 1.36 (95% CI:1.20-1.54) and 2.53 (95% CI:1.99-3.22), respectively.

Conclusion

Optimal glycemic control was associated with lower risk of PC risk and PC-related mortality in T2D. Further multicenter cohort studies are warranted to confirm its oncopreventive strategy.

Introduction

Pancreatic calcification is the most frequent structural change in chronic pancreatitis (CP), but the factors associated with its development are not well understood.

Aims & Methods

We aimed to investigate the risk factors of calcification development in patients with chronic pancreatitis. The study protocol was registered on PROSPERO (CRD42024591837). On September 18, 2024, we conducted a systematic search across three databases (PubMed, EMBASE, and CENTRAL) for studies reporting factors associated with calcification in chronic pancreatitis (CP). Pooled proportions and odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random effects model.

Results

The systematic search resulted in 10,893 articles, from which 85 eligible studies were identified, covering a total of 34568 participants. The odds of calcification were 45% higher in alcoholic compared to idiopathic CP (OR=1.45, CI: 1.00–2.11). Alcohol consumption (OR=2.31, CI: 1.8–2.98) and smoking (OR=2.22, CI: 1.61–3.06) were associated with a two times higher risk of calcification in CP, when compared to non-smokers and non-drinkers. In contrast, the presence of CFTR mutations did not increase the risk of calcification in CP (OR=0.43, CI: 0.11–1.66) compared to patients without CFTR mutations.

Conclusion

Alcohol consumption and smoking were significantly associated with the presence of calcification in CP, making it essential to identify these risk factors and incorporate smoking cessation and alcohol reduction programs into standard care.