Introduction

Despite new therapeutic strategies, substantial proportion of patients with ulcerative colitis (UC) undergo colectomy at some point. Restorative proctocolectomy with ileal pouch ano anastomosis (IPAA) is regarded as intervention of choice in these patients. However, the disease conversion to Crohn´s disease (CD) is reported in up to one third of these patients who necessitate immune suppressive treatment after IPAA. Considering the life-long need for immune suppressive therapy in these patients, ileo-rectal anastomosis (IRA) would represent a good alternative to IPAA in this specific group of patients. Todate, no data are available to predict the UC-CD conversion. One of the possibility to reduce the risk of performing IPAA in patients developing CD in pouch is to use the modified two-stage proctocolectomy approach and identify patients who develop CD endoscopically between colectomy and the restoration of continuity.

Aims & Methods

The aim of the present study was to assess the UC-CD conversion rate identified prior IPAA via ileoscopy.
All patients with UC operated in one tertiary IBD center between 2016 and 2021 were identified in medical records. The main outcome was CD detected at ileoscopy between the first stage operation, i.e. total colectomy with terminal ileostomy and the restoration of continuity either via IPAA or IRA. The ileoscopy was performed between three to six months after colectomy. The secondary outcome was the rate of conversion to CD after IPAA or IRA.

Results

Sixty patients underwent total colectomy (mean age 41 years, range 22-77; 62% were men); seven patients were lost to follow-up, finally the data from 53 patients were analysed. The majority of these patients (36 - 68%) underwent colectomy for therapy resistent chronically active UC, 9 (17%) patients for acute severe UC, 2 patients had benign colonic stenosis, 5 had high-grade dysplasia or colorectal cancer detected at surveillance colonoscopy and one patient had extensive pseudopolyposis.
All resection specimen were reviewed and no histopathological features of CD were found. Three out of the 53 (6%) ileoscopically assessed patients prior IPAA or IRA were diagnosed with CD in prestomal terminal ileum. During the further follow-up, additional 4 patients developped CD, two after IPAA, one with definitive ileostomy in prestomal ileum and one in neoterminal ileum after IRA.
In total 7 out of 53 patients in this cohort developped CD (13%). Using the two stage approach with ileoscopy between colectomy and restoration of continuity, three out of these seven patients with CD convertion in this cohort were detected prior the decision on the type of second-stage operation.

Conclusion

The conversion from ulcerative colitis to Crohn`s disease occurs in a significant proportion of IBD patients after colectomy. Ileoscopy performed between the two stages of restorative proctolectomy is helpfull in detecting these patients and guiding the decision on the type of surgical intervention to restore continuity.

Disclosure

Nothing to disclose.

Introduction

Ulcerative colitis (UC) is associated with debilitating symptoms that impair the quality of life (QoL) of patients; restoration of QoL is an important long-term treatment goal.¹ Upadacitinib (UPA), an oral, reversible Janus kinase inhibitor approved for the treatment of UC, improves health-related QoL (HRQoL) and patient-reported outcomes (PROs) with 1 year (yr) of maintenance therapy.^2-4 This post hoc analysis of the U-ACTIVATE long-term extension (LTE) study evaluated the long-term efficacy of UPA in sustaining PROs and HRQoL outcomes in patients who had received up to a total of 4 years (yrs) of UPA maintenance therapy.

Aims & Methods

This analysis included patients who completed 1 yr (52 weeks [wks]) in the U-ACHIEVE maintenance study and received UPA15 mg once-daily (QD) (UPA15) or UPA 30 mg QD (UPA30) maintenance treatment in the U-ACTIVATE LTE study. Patients receiving UPA15 or UPA30 who achieved clinical remission per Adapted Mayo score at maintenance wk 52 continued their double-blind treatment upon entering the LTE study. Nonremitters receiving UPA15 were escalated to UPA30, those receiving UPA30 continued UPA30, and those assigned to PBO were escalated to UPA15, all in a blinded manner. The UPA UC program was not designed to compare UPA15 and UPA30 doses. Efficacy was assessed at LTE wks 0, 96, and 144 (data cutoff date: 30 June 2024) and included the percentage of patients who achieved absence of abdominal pain, absence of bowel urgency, Inflammatory Bowel Disease Questionnaire (IBDQ) response, IBDQ remission, and a meaningful within-person change (MWPC) in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue; Short-Form Health Survey-36 version 2 Mental Component Score (SF-36v2 MCS), and SF-36v2 Physical Component Score (PCS). Data were reported using as-observed (AO) and modified nonresponder imputation (mNRI) methods (shown in Table). Safety was reported previously.²

Results

This analysis included 369 patients treated with UPA15 or UPA30 at wk 0 of LTE trial. In the AO analysis, patients treated with UPA15 or UPA30 achieved sustained improvements from LTE wk 0 to wk 144 in PROs and HRQoL assessments (Table), including the absence of abdominal pain, absence of bowel urgency, IBDQ response, IBDQ remission; and achieved MWPC in FACIT-Fatigue, SF-36v2 PCS, and SF-36v2 MCS. Similar results were observed for all endpoints with the more conservative mNRI analysis (Table).

Conclusion

Patients with UC who responded to induction therapy and received long-term UPA maintenance therapy showed a sustained absence of symptoms and improvements in HRQoL, suggesting that UPA maintains long-term improvements in patient-reported outcomes.

References

1. Turner D, Ricciuto A, Lewis A, D’Amico F, Dhaliwal J, et al. Gastroenterology. 2021;160:1570–83.
2. Panaccione R, et al. J Crohn’s Colitis. 2025;19(S1):i84-i86 [abstract].
3. AbbVie Inc. RINVOQ (Upadacitinib) [package insert] U.S. Food and Drug Administration website. https://www.rxabbvie.com/pdf/rinvoq_pi.pdf. Revised May 2023. Accessed 25 Feb 2025.
4. AbbVie DG& CoK. RINVOQ. Summary of Product Characteristics. European Medicine Agency website. https://www.ema.europa.eu/en/documents/product-information/rinvoq-epar-product-information_en.pdf. Revised Feb 2025. Accessed 25 Feb 2025.

Disclosure

Funding: AbbVie funded this study (U-ACTIVATE; NCT03006068) and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship.

Acknowledgments: AbbVie and the authors thank the participants, study sites, and investigators who participated in this clinical trial. Paulette A. Krishack, PhD, of AbbVie, provided medical writing support; Angela T. Hadsell, BA, of AbbVie, provided editorial support.

Joana Torres has received grant funding/speaker fees from and/or has participated in advisory boards for AbbVie, Lilly, Takeda, Janssen, and Pfizer.

Corey A Siegel has served as a consultant, advisor, and/or speaker for CME activities and/or received grant funding from AbbVie, BMS, Celltrion, Fresenius, Janssen, Lilly, Napo, Pfizer, Prometheus, Prometheus Labs, Roivant, and Takeda.

Julian Panés received consultancy fees/honorarium from AbbVie, Alimentiv, Athos, Atomwise, Boehringer Ingelheim, Celsius, Ferring, Galapagos, Genentech/Roche, GlaxoSmithKline, Janssen, Mirum, Nimbus, Pfizer, Progenity, Prometheus, Protagonist, Revolo, Sanofi, Sorriso, Surrozen, Takeda, and Wasserman, and has served on a data safety monitoring board for Alimentiv, Mirum, Sorriso, Sanofi, and Surrozen.

Edward V. Loftus Jr. has served as a consultant for AbbVie, Abivax, Amgen, Astellas, Avalo, Biocon, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Fresenius Kabi, Genentech, Gilead, Iota Biosciences, Iterative Health, Janssen, Morphic Therapeutics, Ono Pharma, Takeda, and TR1X Bio; has received research grants from AbbVie, Genentech, Gilead, Janssen, Merck, and Takeda; and is a share owner of Exact Sciences and Moderna.

Remo Panaccione has received consulting fees, speaker fees, and research support from Abbott, AbbVie, Abbivax, Alimentiv Amgen, AnaptysBio, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, GlaxoSmithKline, JAMP Bio, Janssen Pharmaceuticals, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Roche, Sandoz, Sanofi, Satisfai Health, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Viatris, Ventyx, and UCB.

Si Xuan, Nidhi Shukla, Ari Stromberg, Sina Ogholikhan, Leah Rizzo, and Dolly Sharma, are employees of AbbVie and may own stock options.

Gareth Parkesreports personal payments, honoraria, speaker fees, travel grants and/or fellowships from AbbVie, Allergan, Bristol Myers Squibb, Celltrion, Ferring, Galapagos, Janssen, Napp, Takeda, and Tillotts, and directorship and shareholding with Ampersand Health. TR reports personal grants from AbbVie; personal consulting fees from AbbVie, Arena, Aslan, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Ferring, Galapagos, Gilead, GSK, Heptares, LabGenius, Janssen, MonteRosa, Mylan, MSD, Novartis, Numab, Pfizer, Roche, Sandoz, Takeda, UCB and XAP; membership of the ECCO Scientific Committee, and membership in the UEG Scientific Committee; director of Endoread.

Clinical Case Summary

A 39-year-old woman was admitted on June 20, 2024, with a right middle cerebral artery stroke, nine weeks after starting Upadacitinib for ulcerative colitis. She presented with dysarthria, dysphagia, and severe left-sided weakness. CT imaging revealed a wedge-shaped infarction without intracranial hemorrhage (CT head/ Brain MRI).
She was diagnosed with ulcerative colitis in November 2023, she initially responded to Mezavent and steroids but was hospitalized on March 31, 2024 for moderate UC flare, requiring infliximab rescue therapy. The patient presented with four bloody bowel movements and elevated inflammatory markers (CRP>100), confirmed by a Mayo score of 2 on flexible sigmoidoscopy and cytomegalovirus (CMV) infection was excluded. Clostridium difficile tests were negative twice and a CT scan revealed pancolitis. Despite minimal response to rescue therapy, she opted for medical treatment over colectomy.
On April 23, 2024, she began an eight-week induction of Upadacitinib 45 mg, which she tolerated well. However, on June 20, she developed sudden stroke symptoms while eating dinner, including difficulty swallowing, choking, left-sided weakness, and numbness. She had no vascular risk factors or family history of premature cardiovascular conditions. Lupus, and vasculitis work up were unremarkable and extensive thrombophilia screenings were all negative.
Discussion: Thrombosis in IBD patients can result from various potential causes. First of all, Inflammation and hypercoagulability, driven by elevated cytokines like TNF, interleukins, and CRP, activate the coagulation cascade, increasing thrombosis risk.
Conclusion: IBD is a known risk of thromboembolic disease, this risk increased during flare up will raise future research questions regarding extended anticoagulation prophylaxis during flare and uses of Jak stats inhibitor.

References

1. Ferro JM,Oliveira Santos M. Neurology of inflammatory bowel disease. J Neurol Sci. 2021 May 15;424:117426. doi: 10.1016/j.jns.2021.117426. Epub 2021 Mar 27.

2. Solitano V.Thrombosis in IBD in the Era of JAK Inhibition. Curr Drug Targets. 2021;22(1):126-136. doi: 10.2174/1389450121666200902164240.

3. Guiu A,a new opportunistic pathogen associated with cystic fibrosis?]Enferm Infecc Microbiol Clin. 2014 Oct;32(8):497-501. Spanish.DOI: 10.1016/j.eimc.2013.08.003

4. Tan JT, Ng DP.Genetic variation in KCNQ1 associates with fasting glucose and beta-cell function: a study of 3,734 subjects comprising three ethnicities living in Singapore.Diabetes. 2009 Jun;58(6):1445-9.DOI: 10.2337/db08-1138

5. Reddy VB.The burden of diverticular disease on patients and healthcare systems.Gastroenterol Hepatol (N Y). 2013 Jan;9(1):21-7.

6. Kim WJ.Major constituents and antimicrobial activity of Korean herb Acorus calamus.Nat Prod Res. 2011 Aug;25(13):1278-81.DOI: 10.1080/14786419.2010.513333

7. Lou JS, Effect of expectancy and personality on cortical excitability in Parkinson's disease.Mov Disord. 2013 Aug;28(9):1257-62.DOI: 10.1002/mds.25471PMID: 23630185

8. Parra-Izquierdo I,Janus kinase inhibitors ruxolitinib and baricitinib impair glycoprotein-VI mediated platelet function.Platelets. 2022 Apr 3;33(3):404-415.DOI: 10.1080/09537104.2021.1934665Epub 2021 Jun 7.

9. Kwak SH, Incidentally found resectable lung cancer with the usage of artificial intelligence on chest radiographs.PLoS One. 2023 Mar 10;18(3):e0281690.DOI: 10.1371/journal.pone.0281690PMID: 36897865;

10. Nguyen GC, et al. Consensus Statements on the Risk, Prevention, and Treatment of Venous Thromboembolism in Inflammatory Bowel Disease: Canadian Association of Gastroenterology. Gastroenterology. 2014;146(3):835–848. doi:10.1053/j.gastro.2014.01.042

Introduction

The estimated global prevalence of biopsy-confirmed celiac disease (CeD) is 0.7% and sero-positive prevalence is 1.4%. Differences in definitions of CeD cases and at-risk populations, as well as underdiagnosis, may affect accurate estimation of the size of the diagnosed CeD population. In this study, we calculated the 10-year prevalence of diagnosed CeD in the USA using different CeD case definitions and at-risk populations.

Aims & Methods

A prevalence analysis of CeD cases was conducted using data collected from the Optum Clinformatics^® Data Mart, a US claims database. Prevalence calculations were based on two different definitions of CeD cases. Case definition 1 included any of the following: 1) International Classification of Diseases (ICD)-9/-10 diagnostic codes for CeD (≥ 1 inpatient or ≥ 2 outpatient codes), 2) tissue transglutaminase immunoglobulin A (tTG-IgA) positive serology or 3) biopsy-confirmed CeD (defined as esophagogastroduodenoscopy [EGD] followed by an ICD diagnostic code for CeD used as proxy). Case definition 2 was defined as the first ever positive tTG-IgA test followed by biopsy-confirmed CeD. The prevalence of diagnosed CeD was estimated for each study year from 2013 to 2022. Prevalence estimations were age- and sex-standardized using 2022 US Census data.

Results

The total population (denominator) comprised ~81 million individuals; of whom, 110,140 had ≥ 1 inpatient or ≥ 2 outpatient diagnostic codes for CeD, 41,184 had ≥ 1 positive tTG-IgA test and 44,641 had biopsy-confirmed CeD. Among all individuals that were tested for tTG2-IgA, 0.85% (95% confidence interval [CI]: 0.82, 0.89) were positive for CeD. The age- and sex-standardized prevalence of diagnosed CeD according to case definition 1 modestly increased from 0.27% (95% CI: 0.27, 0.27) in 2013 to 0.35% (0.34, 0.35) in 2022. Over the same time period, the age- and sex-standardized prevalence of diagnosed CeD according to case definition 2 increased from 0.01% (0.01, 0.01) to 0.03% (0.03, 0.03), respectively.

Conclusion

The overall prevalence of diagnosed CeD in the USA modestly increased from 2013 to 2022. During this same time period, the proportion of patients who underwent an EGD after a positive tTG-IgA test steadily rose. Validation of the CeD case definitions used in this study will be important to enable these results to be replicated or refuted. Furthermore, a standardized and validated CeD case definition will support comparisons between studies and inform better clinical care/disease management.

Disclosure

MA, SM, NC, KG and DAL are employees of Takeda Development Center Americas, Inc. and receive stock or stock options.

Introduction

The LIR!C trial demonstrated that laparoscopic ileocaecal resection (ICR) is a cost-effective alternative to infliximab therapy (IFX) in patients with uncomplicated ileocaecal Crohn’s disease (CD), with comparable quality of life outcomes. The aim of this study was to assess the 10-year follow-up of patients enrolled in the LIR!C trial.

Aims & Methods

This retrospective follow-up study included patients from the original LIR!C trial, a multicentre randomized controlled trial comparing ICR to IFX treatment in patients with ileal CD. Long term follow-up data were collected between February 3 and April 14, 2025. Data extraction was focused on initiation or switch of IBD treatments (corticosteroids, immunomodulators and/or advanced medical therapies) and (re)-resections. The follow-up period ranged from trial enrolment to the last visit with the gastroenterologist or surgeon. Primary outcomes were: (1) proportion of patients in clinical remission without therapy switch (no medical therapy or re-resection in the ICR group, and continuation or the cessation of IFX in case of remission in the IFX group), and (2) therapy-free remission, defined as clinical remission without IBD medication and (re)resections.

Results

Follow-up data were available from 60 ICR patients and 57 IFX patients (87% of 134 patients originally included). The median follow-up time was 12 years (IQR 9-14). The clinical remission rate without therapy switch was 40% in the ICR group compared to 26.3% in the IFX group (p=0.117). Of the 60 ICR patients, 24 (40%) had no additional therapy, 13 (21.7%) received an immunomodulator, 18 (30%) biological therapy and 5 (8.3%) underwent a second resection after biological treatment. In the IFX group, 33 (57.9%) required an ICR of whom 25 (75.8%) had previously received second-line biological treatment. Additionally, 7/57 patients (12.3%) were therapy free, 8 (14%) continued IFX treatment, 6 (10.5%) received other biological treatment, and 3 (5.3%) switched to an immunomodulator. Therapy-free remission was significantly higher in the ICR group when compared to the IFX group (40% vs 12%, p < 0.001).

Conclusion

After 10 years of follow-up, the clinical remission rate without therapy switch was comparable between both groups, highlighting the long-term durability of both treatment approaches. The majority of IFX patients needed ICR within 10 years of follow-up. 40% of the ICR group did not require any additional therapy further supporting ICR as first-line treatment option in ileal CD.

References

Ponsioen, C. Y., de Groof, E. J., Eshuis, E. J., Gardenbroek, T. J., Bossuyt, P. M. M., Hart, A., Warusavitarne, J., Buskens, C. J., van Bodegraven, A. A., Brink, M. A., Consten, E. C. J., van Wagensveld, B. A., Rijk, M. C. M., Crolla, R. M. P. H., Noomen, C. G., Houdijk, A. P. J., Mallant, R. C., Boom, M., Marsman, W. A., Stockmann, H. B., … LIR!C study group (2017). Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial. The lancet. Gastroenterology & hepatology, 2(11), 785–792. https://doi.org/10.1016/S2468-1253(17)30248-0

Disclosure

GD'H served as a consultant for AbbVie, Alimentiv, AstraZeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Exeliom Biosciences, Johnson & Johnson, Pfizer, and Takeda; and has received speakers bureau fees from AbbVie, Eli Lilly, Pfizer, Bristol Myers Squibb, and Takeda.