Introduction

Neoplasia detection in inflammatory bowel disease (IBD) poses a clinical challenge. We have previously reported the efficacy of a novel computer aided detection (CADe) algorithm for use in IBD (CADe-IBD) in images and videos. CADe-IBD is designed for use in high-definition white light endoscopy which may reduce operator variability which comes with chromoendoscopy. The added value of CADe-IBD is yet to be explored which this study aims to address.

Aims & Methods

Based on pilot data this study was powered as a superiority test, with 90% power for increased sensitivity of non-expert endoscopists with CADe-IBD compared to without CADe-IBD. 10 experienced and 11 less experienced endoscopists were asked to review short video clips of high definition white-light IBD endoscopy on a bespoke computer software designed by NEC Japan. The videos were watched once without CADe-IBD and then again with CADe-IBD when the videos were randomly redistributed to reduce recall bias. After each video the endoscopist was asked to select ‘polyp’, ‘no polyp’ or ‘uncertain’. If the endoscopist selected ‘polyp’ for a video they were asked to annotate the suspected abnormality.

Results

The study included 285 videos from IBD colon. 131 videos had lesions which showed a diverse range of size, morphology, histology and background mucosal inflammation. Videos were from all 3 major endoscopy processors (Pentax, Olympus and Fuji).
The standalone CADe-IBD sensitivity and specificity were 94.7% and 70.8% respectively. In comparison, experienced endoscopist sensitivity and specificity were 90.5% and 80.2% and less experienced endoscopists sensitivity and specificity of 73.7% and 82.1%. CADe-IBD sensitivity was significantly better than both experts and non-exerts (p<0.05).
With the addition of CADe-IBD, less experienced endoscopists sensitivity increased significantly to 89.2% (p <0.01) and specificity remained similar at 81.0%. Experienced endoscopist sensitivity also improved with CADe-IBD to 93.4% which was again statistically significant (p<0.05).
Sub-analysis was performed based on neoplastic or non-neoplastic histology, polypoid (Paris Is, Isp, Ip) and non-polypoid (Paris IIa/IIb/IIc) morphology and Mayo endoscopic sub-score for mucosal inflammation (Table 1).

Conclusion

CADe-IBD has a standalone performance which is superior to both less experienced and experienced endoscopists. The addition of CADe-IBD significantly improved lesion detection regardless of experience. This superior performance was observed in neoplastic lesions, non-polypoid lesions and in the presence of mild background mucosal inflammation which is of high clinical importance. This calls for a head to head comparison of CADe-IBD with conventional surveillance techniques.

References

Abdelrahim M, Siggens K, Iwadate Y, et al New AI model for neoplasia detection and characterisation in inflammatory bowel disease Gut 2024;73:725-728.

Disclosure

Professor Bhandari has received research grants or is the advisory board for Fujifilm, Boston, Olympus, Pentax, 3-D matrix, NEC (Japan) and Medtronic

Introduction

The BIOSTOP Trial is a prospective, multicenter, randomized, controlled, open-label study conducted in Norway to evaluate the two-year outcomes of tumor necrosis factor-alpha (anti-TNF) antibody withdrawal in patients with ulcerative colitis (UC) in sustained clinical and endoscopic remission. Prior non-randomized studies have suggested that approximately half of such patients maintain remission after anti-TNF discontinuation and that reintroduction of anti-TNF therapy is generally effective and safe in the event of relapse.

Aims & Methods

A total of 174 UC patients in confirmed clinical and endoscopic remission were enrolled across 19 gastroenterology centers between June 2017 and December 2020 and randomized 1:1 to either continue or discontinue anti-TNF therapy. Eligibility criteria included at least 12 months of first-line anti-TNF maintenance treatment, clinical remission, fecal calprotectin <200 µg/g, and endoscopic remission (Mayo endoscopic score 0 or 1). Two-year follow-up data were available for 172 patients (86 in each group). In 156 of the patients endoscopies were available for central reading (77 in the withdrawal group and 79 in the maintenance group). The primary endpoint was sustained endoscopic remission at two years.

Results

At two years, central reading of follow-up colonoscopies confirmed endoscopic remission in 64 of 77 patients (83%, 95% CI 71.8 – 93.1) in the anti-TNF withdrawal group, compared to 77 of 79 patients (96 %, 95 % CI 92.1 – 100.8) in the anti-TNF maintenance group. The non-inferiority primary endpoint of the study was thus not met. During the study period, 48% of patients in the withdrawal group and 88% in the maintenance group remained in sustained clinical and endoscopic remission without relapse. Among the 45 patients in the withdrawal group who experienced endoscopic confirmed relapse, 28 (62%) resumed anti-TNF therapy, with 26 achieving both clinical and endoscopic remission. Additionally, 10 of 13 patients with mild relapses achieved endoscopic remission with optimized non-biologic therapy. There were no difference in serious adverse events between the groups.

Conclusion

After two years, 83% of patients in the anti-TNF withdrawal group and 96% in the maintenance group were in clinical and endoscopic remission, including those who experienced flares and achieved new remission after reintroduction of anti-TNF or optimized non-biologic therapy. Nearly half of the patients maintained remission without anti-TNF, and the majority of relapses were effectively managed. These findings suggest that anti-TNF withdrawal is a safe option for selected UC patients in confirmed remission, provided they are monitored closely.
Trial Registration: ClinicalTrials.gov Identifier: NCT03011268; EudraCT Number: 2016-001409-18. Trial completion date: 31 January 2025.

Disclosure

No disclosures

Introduction

JAK inhibitors (JAKi) are small molecules capable of crossing the placenta via passive diffusion or active extracellular transport from early pregnancy.¹ Data on the risks of in utero JAKi exposure are limited,² particularly regarding pregnancy outcomes, infant infections, vaccine responses, and childhood development.

Aims & Methods

We conducted a multicenter retrospective JAKi and pregnancy observational study supported by the ECCO Collaborative Network for Exceptionally Rare Case Reports (CONFER). Pregnant women with inflammatory bowel disease (IBD) exposed to tofacitinib (TOFA), upadacitinib (UPA), or filgotinib (FILGO) during pregnancy were enrolled from 21 centers across 15 countries. Data collected included maternal demographics, IBD characteristics, disease activity, medication use - including timing and duration of JAKi exposure - along with maternal, pregnancy, and infant outcomes.

Results

Of 43 JAKi exposed pregnancies, 17 (39.5%) were unplanned. Disease activity was present in 22 (51.2%) of the pregnancies. One-in-five women initiated JAKi in pregnancy (n=8, 18.6%). Abortion occurred in 8 cases, at a median gestational age (GA) of 8.5 weeks (range 3-16). Of these, 3 (7.0%) were spontaneous and 5 (11.6%) induced, with two terminations due to concerns about potential adverse effects of JAKi treatment. Of the remaining 35 pregnancies 26 (74.3%) were exposed to TOFA (5 mg BID (n=9), 10 mg BID (n=17)), 8 (22.9%) to UPA (30 mg daily (n=2), 45 mg daily (n=6)) and one (2.9%) to FILGO (200 mg daily). The majority received JAKi treatment throughout pregnancy (n=24, 68.6%). Discontinuation of JAKi during the 1^st or 2^nd trimester was followed by disease activity in 7 of 11 cases (63.6%). Maternal complication risk was low: no cases of DVT or (pre)eclampsia; premature rupture of membranes (GA 34–37) occurred in 3 cases, and 4 women required hospitalization due to infection or other complications. Among 35 live births, one infant (2.9%) was preterm (GA 34), three (8.6%) were small for gestational age, one (2.9%) had an Apgar score <7 at 5 minutes, and no congenital abnormalities were reported. Follow-up infant data are shown in table 1. One-third of breastfeeding women continued JAKi treatment. A high adherence rate to the national immunization schedule was seen. Three (8.6%) skipped the live rotavirus vaccine due to in uteroJAKi exposure. No adverse effects were reported following live attenuated or inactivated vaccines, and no malignancies were observed.

Conclusion

In this global multicenter study of JAKi exposure during pregnancy in women with IBD, maternal complication rates were low, and no increased risk of adverse pregnancy outcome were observed among live births. While disease activity was common, particularly following early discontinuation of JAKi, infant outcomes - including development, infection risk, and vaccine response - were reassuring. These findings provide important preliminary safety data to guide decision-making regarding the use of JAKi in pregnancy, though further prospective studies are needed to confirm long-term safety.

References

1. Fein KC, Arral ML, Kim JS, et al. Placental drug transport and fetal exposure during pregnancy is determined by drug molecular size, chemistry, and conformation. J Control Release 2023;361:29-39.
2. Torres J, Chaparro M, Julsgaard M, et al. European Crohn's and Colitis Guidelines on Sexuality, Fertility, Pregnancy, and Lactation. J Crohns Colitis 2023;17:1-27.

Disclosure

M. Julsgaard: Advisory board for AbbVie. G. Santana: Speaker and advisory board for pfizer.