bluuebunny/crossref_metadata_2025 huggingface dataset:
P658 Safety and efficacy of MH002, an optimized live biotherapeutic product, for the treatment of mild to moderate ulcerative colitis: a first-in-disease, double-blind, randomized clinical trial
Authors: Vermeire S , Dewint P , Vansteelant M , Peterka M , Štěpek D , Kierkuś J , Wiernicka A , Napora P , Wolański Ł , Kopoń A , Magro F , Pinheiro I , Possemiers S , Haazen L , Bolca S
Published: January 2024

Background

Treatment options for patients with mild to moderate ulcerative colitis (UC) failing 5-ASA are limited. MH002 is an optimized consortium of 6 non-pathogenic, well-characterized commensal bacteria with immune modulating, wound healing and gut barrier protective effects. This study evaluated the safety, efficacy, and mechanistic effects of MH002 in mild to moderate UC.

Methods

In this 2:1-randomized, double-blind, placebo-controlled first-in-disease study (EudraCT 2020-001355-33), 45 patients with mild to moderate active UC (Modified Mayo Score [MMS] =4-8 but including Mayo Endoscopic Sub-score [MES] ≥2) received treatment with 400mg MH002 or placebo (PBO) once daily for 8 wks. Full colonoscopies with biopsies were performed at baseline and wk8, biopsies and endoscopy videos were scored by blinded central readers. The primary endpoint was the rate of treatment-emergent adverse events (TEAEs). Exploratory efficacy endpoints included clinical remission (MMS ≤2 with all sub-scores ≤1 and rectal bleeding sub-score =0), endoscopic improvement (MES ≤1), and UC-100 and biomarker normalisation (C-reactive protein [CRP] ≤5mg/L, faecal calprotectin [FCP] ≤250mg/kg). Changes from baseline (CFBL) in MES and stool consistency (Bristol Stool Form Scale) were also evaluated.

Results

MH002 was safe and well tolerated: a TEAE was reported in 11/31 (35%) patients with MH002 and in 8/14 (57%) with PBO. Most TEAEs were mild and unrelated to study treatment. Early discontinuations (7/45; 16%) occurred similarly in both groups. At wk8, patients achieved clinical remission, endoscopic improvement, and biomarker improvements at higher rates with MH002 vs PBO (Table 1). Clinical remission rates were 14% for MH002 vs 7% for PBO (Per-protocol Set [PPS]: 18% vs 0%). Significant differences in favour of MH002 over PBO were seen in the CFBL for MES at wk8 (P=0.05, 1-sided Wilcoxon) and for stool consistency at wk2 (P=0.0057, 1-sided Student t). In total, 14/45 (31%) and 36/42 (86%) patients had elevated CRP and FCP levels at baseline, resp. Of these, more patients treated with MH002 achieved normalisation at wk8 (CRP: 60% vs 25%; FCP: 36% vs 15%). Decreases in FCP and stool consistency with MH002 were observed as early as wk2 and were greater than with PBO through wk8 (Fig 1).

Conclusion

MH002 treatment was safe and well tolerated and resulted in clinically meaningful improvements in disease activity and inflammatory parameters. MH002 therefore represents a promising new treatment for mild to moderate UC patients insufficiently controlled with 5ASA. These results warrant further development in a phase 2/3 study.
P666 Accuracy of information given by ChatGPT for patients with Inflammatory Bowel Disease in relation to ECCO guidelines
Authors: Farrugia Y , Sciberras M , Gordon H , Furfaro F , Allocca M , Torres J , Arebi N , Fiorino G , Iacucci M , Verstockt B , Magro F , Katsanos K , Fenech V A , Chetcuti Zammit S , Ellul P
Published: January 2024

Background

As acceptance of AI platforms increases, more patients will consider these tools as sources of information. The ChatGPT architecture utilizes a neural network to process natural language, thus generating responses based on the context of input text. The accuracy and completeness of ChatGPT3.5 in the context of Inflammatory Bowel Disease (IBD) remains unclear.

Methods

In this prospective study, 38 questions worded by IBD patients were inputted into ChatGPT3.5. The following topics were covered: 1) Crohn’s Disease, Ulcerative Colitis, and malignancy, 2) maternal medicine 3) infection and vaccination 4) complementary medicine. Responses given by ChatGPT were assessed for accuracy (1 – completely incorrect to 5 – completely correct) and completeness (3-point Likert scale; range 1 – incomplete to 3 – complete) by 14 expert gastroenterologists, in comparison with relevant ECCO guidelines.

Results

In terms of accuracy, most replies (84.2%) had a median score of ≥4 (IQR:2) and a mean score of 3.87 (SD: +/- 0.6). For completeness, 34.2% of the replies had a median score of 3 and 55.3 % had a median score of between 2 and <3. Overall, the mean rating was 2.24 (SD: +/- 0.4, Median:2 IQR :1). Though group 3 and 4 had a higher mean for both accuracy and completeness, there was no significant scoring variation between the 4 question groups (Kruskal-Wallis test p:>0.05) (Table 1). However, statistical analysis for the different individual questions revealed a significant difference both for accuracy (p<0.001) and completeness (p<0.001). The questions which rated the highest for both accuracy and completeness were related to smoking, while the lowest rating was related to screening for malignancy and vaccinations especially in the context of immunosuppression and family planning.

Conclusion

This is the first study to demonstrate the capability of an AI-based system to provide accurate and comprehensive answers to real-world patient queries in IBD. AI systems may serve as a useful adjunct for patients, in addition to standard of care in clinic and validated patient information resources. However, responses in specialist areas may deviate from evidence-based guidance and the replies need to give more firm advice.
P670 Intestinal Motility Changes in Patients Undergoing Removable Stent Treatment for Focal Crohn’s Disease Strictures
Authors: Das R , Singh R , Menys A , Din S , Hoad C , Lund J , Cole A
Published: January 2024

Background

Management and assessment of fibrostenotic Crohn’s disease(CD) is a research priority. Deep phenotyping is key for effective therapeutic development. In this study, we explore MRI assessed bowel motility before and after endoscopic stent treatment of focal fibrotic strictures in patients with CD.

Methods

Patients (n = 12, median age = 51 y) undergoing removable stent treatment were recruited as part of an approved study. Average CD diagnosis was 31y (range 16-57 y). All strictures were fibrotic in nature- three were de novo, while the remaining were anastomotic (ileocolonic). All patients had symptoms attributable to focal stricturing. Each patient had an MR – Enterography (MRE) scan (median 21 weeks) before and after (median 17 weeks) stent dilation. MR – Enterography (MRE) protocol included oral preparation, anatomical and cine ‘motility’ sequences across the abdomen in 20s breath hold (1 image/second). Motility sequences were processed with CE/FDA cleared GIQuant (Motilent, UK) to produce a quantitative map from which, objective data could be generated across the bowel. Stricture assessment was performed by a consultant radiologist.

Non parametric statistics were used to investigate the following questions:

1. Was the baseline regional motility (mean, range) at stricture, dilation and morphologically normal bowel different across patients (Kruskal-Wallis)?

2. What were the changes in stricture motility pre and post stent placement (Wilcoxin Rank)?

3. Was stricture motility associated with stricture morphology (Spearman’s Rho)?

Results

1. Motility at the stricture (126, range 62 to 139), pre-stenotic terminal ileum (252, range 80 to 478) and the global small bowel (269, range 166 to 339) was varied across the cohort (P < 0.001).

2. All patients had improvement in symptom scores & reporting, without change in stricture motility (P = 0.94).

3. A positive change in stricture motility was associated with reduced length of pre stricture dilatation (R = 0.64, P = 0.02)

Conclusion

Strictured intestine displayed reduced motility compared with adjacent bowel segments. While reduced, peristalsis was still present although paired analysis suggested no change pre and post stent stricture management. This implies that symptomatic relief was not related to altered peristalsis across the study. Finally, the length of dilation did appear to be associated with dynamic changes in stricture motility. In summary, as noted in stent-treated CD strictures, a dynamic physiological environment exists which can be captured with Cine MRI. These motility assessments, which have been studied as a proxy indicator of active CD, represent the first reported dynamic motility outcomes following stricture intervention.
P697 Short- and long-term outcomes following biologic use before non-conventional stricureplasty for Crohn’s Jejunoileitis
Authors: Belkovsky M , Cohen B , Sommovilla J , Hull T , Holubar S
Published: January 2024

Background

Non-conventional strictureplasties, specifically the Finney and Michelassi technique, are bowel-preserving surgical techniques for diffuse jejunoileal Crohn’s Disease (CD). We investigated the association of biologic use during non-conventional strictureplasty for Crohn's jejunoileitis and its short- and long-term outcomes.

Methods

We conducted a retrospective review of all patients with CD who underwent non-conventional strictureplasty at our centre, e.g., side-to-side antiperistaltic strictureplasty (SSAS) according to the Finney or modified Finney technique, or side-to-side isoperistaltic (SSIS) according to the Michelassi or modified Michelassi techniques from January 2000 to October 2022. Patients were categorized into BIO and NoBIO groups based on their uninterrupted use of biologics until the moment of surgery. Our outcomes of interest were: (a)30-day complications; and (b)surgical recurrence. Statistical analysis was performed using R version 4.3.1.

Results

A total of 71 patients underwent non-conventional strictureplasty: 80 SSAS and 14 SSIS. Group 1 had 17 patients in which 15 SSAS and 3 SSIS were performed. Group 2 had 54 patients in which 65 SSAS and 11 SSIS were performed. Most patients also underwent concurrent Heineke-Mikulicz strictureplasty in 49 patients (69%) and concurrent small bowel resection in 53 patients (74.6%). The patients in the BIO and NoBIO groups had similar baseline characteristics (Table 1). No differences were observed in perioperative outcomes (Table 2). No difference was observed when comparing surgical recurrence rates, but a longer median time to recurrence was observed in the BIO group (4.7 vs. 4.4 years, p=0.004).

Conclusion

Biologic use at the time of non-conventional strictureplasty for diffuse jejunoileal Crohn’s disease is safe and is associated with a longer median time to recurrence.
P698 Effectiveness and Safety of Ustekinumab for Ulcerative Colitis: A Brazilian Multicentre Real-World Observational Study
Authors: Parra R , Chebli J M F , Freitas Cardoso de Azevedo M , Chebli L A , Zabot G P , Cassol O S , Fróes R D S B , Santana G O , Lubini M , Magro D O , Imbrizi M , Moraes A C S , Teixeira F V , Alves Jr A J T , Gasparetti Junior N L T , Ferreira S D C , Queiroz N S F , Kotze P G , Féres O
Published: January 2024

Background

Real-world data on the effectiveness and safety of ustekinumab (UST) in ulcerative colitis (UC) are lacking in Latin America. In this study, we aimed to describe the effectiveness and safety of UST in a real-world multicentre cohort of Brazilian patients with UC.

Methods

We conducted a multicentre retrospective observational cohort study, including patients with moderate to severe UC (Total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who received UST. The co-primary endpoints were clinical remission, defined as a total Mayo score ≤2 at 1 year, with a combined rectal bleeding and stool frequency subscore of ≤1, and endoscopic remission (endoscopic Mayo subscore of zero) within one year from baseline. Secondary endpoints included clinical response between weeks 12-16, endoscopic response within one year of starting UST, steroid-free clinical remission at week 52, and biochemical remission at week 52. We also evaluated UST treatment persistence and safety.

Results

A total of 50 patients were included (female, n=36, 72.0%), with a median disease duration of 9.2 years (1-27). Most patients had extensive colitis (n=38, 76.0%), and 43 (86.0%) were steroid-dependent at baseline. Forty patients (80.0%) were previously exposed to biologics (anti-TNF drugs, n=31; vedolizumab [VDZ], n=27). The co-primary endpoints of clinical remission and endoscopic remission at 1 year were achieved by 50.0% and 36.0% of patients, respectively. Clinical response at weeks 12-16 was 56.0%, endoscopic response, steroid-free clinical remission, and biochemical remission at week 52 were 68.0%, 67.4%, and 50.0%, respectively. The UST treatment persistence rates at 24 months was 73.7%. During the follow-up, 10 patients (20.0%) were hospitalized, mostly due to disease progression, and three patients required colectomy. Nine patients (18.0%) discontinued the drug mainly due to a lack of effectiveness. Twenty-six adverse events (AEs) were reported, 15 of which were considered as serious AEs.

Conclusion

This is the first real-world experience study to report the effectiveness and safety of UST specifically in a Latin American population. In this real-world cohort of difficult-to-treat UC patients, UST was associated with improvements in clinical, biochemical, and endoscopic outcomes. The safety profile was favorable, consistent with the known profile of UST.
P699 Identification of A Novel Activated NK-Associated Gene Score Associated with Diagnosis and Biological Therapy Response in Ulcerative Colitis
Authors: Dong S , Zhang Y , Ye L , Cao Q
Published: January 2024

Background

Natural killer (NK) cells are associated with the pathogenesis of ulcerative colitis (UC), while their precise contributions remain unclear. The present study sought to investigate the diagnostic value of activated NK-associated gene score (ANAG score) in UC and evaluate its predictive value in biological therapy response.

Methods

Bulk RNA-seq datasets were obtained from the Gene Expression Omnibus (GEO). GSE11223, GSE87466, and GSE92415 were integrated for diagnosis value analysis. GSE206285 and GSE92415 were used to analyze the prediction of response to ustekinumab (UST) and golimumab (GLM), respectively. The immune infiltration landscape was estimated by single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. Differentially expressed genes (DEGs) correlated with activated NK cells were identified as activated NK-associated genes (ANAGs). Key ANAGs were screened by protein-protein interaction (PPI) analysis and least absolute shrinkage and selection operator (LASSO) regression.

Results

The immune infiltration analysis revealed a higher abundance of activated NK cells in non-inflamed UC tissues. 54 DEGs correlated with activated NK cells were identified as ANAGs. PPI analysis and LASSO regression were utilized to screen out 4 key ANAGs (SELP, TIMP1, MMP7, and ABCG2). ANAG score was established with the following formula: ANAG score = 0.628 * SELP + 1.574 * TIMP1 + 0.740 * MMP7 - 0.361 * ABCG2 – 18.940. The ANAG scores were significantly higher in inflamed tissues, as well as in biological therapy non-responders (NR) tissues before treatment. The ANAG score demonstrated excellent diagnostic value (AUC = 0.979). Furthermore, according to quartile stratification, patients with a higher ANAG score before treatment were more likely to experience lack of response to ustekinumab and golimumab.

Conclusion

This study established a novel ANAG score with the ability to precisely diagnose UC and distinguish the efficacy of biological treatment.
P706 Tofacitinib in Moderate to Severe Ulcerative Colitis patients naïve to biological therapy: A prospective real world analysis of efficacy and safety
Authors: Banerjee R , Dhanush M , Raghunathan N , Pal P , Joshi V , Patel R , Godbole S , Akki Y , Valluri S , Nagasuri P , Haridas A
Published: January 2024

Background

Tofacitinib is an oral non-selective Janus Kinase inhibitor approved for Ulcerative colitis (UC) after the failure of biological therapy. Tofacitinib as first line therapy in biologic naive patients has not been evaluated.

Methods

We conducted a prospective study to assess the safety and efficacy of Tofacitinib as first line therapy in biologic naive moderate to severe UC. Tofacitinib was given at a dose of 10mg BD for 8 weeks followed by de-escalation to 5mg BD maintenance in responders. Dose escalation was done for relapses. Demographics, disease characteristics, concomitant medication, adverse events, severity and time to relapse were recorded. Clinical response and remission (defined as partial Mayo score: PMS decrease ≥2 and PMS ≤1 respectively) were measured at 4 weeks, 8 weeks, 24 weeks and 52 weeks. Endoscopic response (UCEIS score decrease ≥2) and remission (UCEIS 0-1) were assessed at 1 year. Time to event analysis was done to evaluate the cumulative rate of clinical response.

Results

176 patients (136 biologic naive, 58% male; median age 40y [IQR:31-48y]) were included. Median baseline PMS and UCEIS score were 5 (IQR: 5-7 and 4-6 respectively) (Table 1). Of the biologic naïve cohort, clinical response was achieved in 68.4% and 79.4% at 4 and 8 weeks respectively. Clinical remission was achieved in 45.6%(4-weeks) and 55% (8-weeks). Maintenance of remission was seen in 44.1% and 32.4% in 24 and 52 weeks respectively (Fig1A). There was a significant reduction in PMS from baseline to end of 8-weeks (p<0.001) (Fig 1B). Corticosteroid-free clinical remission was achieved in 64.8% at 24-weeks. 106 patients (77.9%) maintained response till last follow-up. 11 relapsed after dose de-escalation (median time of 5m [range 3-22m]. 7/11 responded to dose escalation to 10mg. Endoscopic response was noted in 62.5% and remission in 33.9% with significant reduction in UCEIS from baseline to 52-weeks(p<0.001) (Fig 1B). Severe and minor adverse events were noted in 4 and 3 patients respectively (Table 1). Overall 1/3 of patients discontinued therapy at 24-weeks (14%) and 52 weeks (10%).

No significant difference in proportion of clinical or endoscopic remission was observed between the biologic naïve and those with history of prior biologic usage (n=31, median time from withdrawal of biologics to Tofacitnib initiation=9 months).

Conclusion

Tofacitinib was effective in induction of clinical remission in more than half of biologic naive, moderate to severe UC . Three-fourth of these patients continued to be in remission at one year with few serious adverse events. Tofacitinib can be considered as upfront oral therapy after failure of conventional management.
P714 Immunogenicity and safety of adjuvated recombinant zoster vaccine in IBD patients on different immunosuppressive therapies
Authors: Franco M , De Bona M , Brun P , Bortoluzzi M , Nappo A , Zaetta D , Roncen E , Riguccio G , Boito C , Piselli P , Castagliuolo I , Savarino E V , Buda A
Published: January 2024

Background

Aberrant immune regulation and the use of immunosuppressive therapy make IBD patients more susceptible to complications of primary Varicella Zoster Virus (VZV) infection and significantly increase the risk of Herpes Zoster (HZ). HZ can be prevented by vaccination and RZV is the first HZ vaccine approved for immunocompromised persons. Limited data on immunogenicity and safety of RZV in immunosuppressed IBD patients are available. We investigated humoral and cell-mediated response and safety of RVZ vaccination in IBD patients under different immunosoppressive therapies.

Methods

In this prospective single centre study, adult IBD patients were enrolled and vaccinated with 2 doses of RZV between May and July 2022. Different immunosuppressive regimens (anti-metabolites, anti-TNF mono and combination therapy; ustekinumab and vedolizumab monotherapy; mofetyl mycofenolate/steroid combination therapy) were not discontinued and the administration schedule maintained. Immunogenicity was evaluated by quantitative detection of serum IgG anti-VZV antibodies and anti-VZV glycoprotein E (gE) antibodies before and 1 month after vaccination completion using ELISA. Reactogenicity was evaluated by diary cards reporting adverse events for 7 days after each dose. Events were graded from 1 (mild, not interfering with everyday activities) to 3 (severe, preventing normal everyday activities). Disease activity was assessed by SCCAI and HBI before vaccination, 7 and 30 days after each dose.

Results

Vaccination was completed in 104 (98.1%) out of 106 enrolled patients (median age 49.7 years, 59.4% male; 55.7% UC, 44.3% CD). Humoral response was observed in all patients, with a significant increase of anti-VZV antibodies (median UTI 23.8; IQR: 20.2-26.2 vs median UTI 419; IQR: 20.2-26.2, 376-458, p<0.001, median 17.8 fold increase, figure 1) and anti-gE antibody concentration compared to baseline (median OD 0.24; IQR: 0.21-0.26 vs OD 0.53; IQR:0.4-0.6, median 2.3 fold increase, p<0.001, figure 1). Imunosuppressive agents, either in mono or combination therapy, did not influence anti-VZV titre, anti-gE concentration and CMI response. Local and systemic solicited reactions after any dose were reported in 96.2% (grade 3=24.8%) and 88.6% (grade 3=33.3%) of patients respectively, with higher grade of intensity after the second dose. No severe adverse events related to vaccination were observed; 2 patients (1.9%) reported a disease flare.

Conclusion

RZV vaccine is able to induce a robust gE-specific humoral immune response. The type and intensity of immunosuppressive regimens did not influence humoral immunogenicity. RZV vaccination was safe and well tolerated in terms of both reactogenicity and exacerbation of disease.
P731 Relapse rate following withdrawal of anti-TNF therapy in patients with inflammatory bowel disease: A single-center experience
Authors: Sina Dr. M , Pemaj X , Djegsi A , Telaku S , Prifti S
Published: January 2024

Background

Discontinuation of anti–tumor necrosis factor alpha treatment (anti-TNFα) in patients with inflammatory bowel disease (IBD) poses a significant risk for relapse. The aim of this study is to analyze relapse rates and to possibly identify factors associated with relapse in IBD patients after treatment cessation with anti-TNFα.

Methods

This is a prospective study conducted at University Clinic of Gastroenterology in Albania from 2019-2022. IBD patients who discontinued biologic therapy with infliximab (IFX) or adalimumab (ADA) were included. All the patients discontinued therapy due to reimbursement issues. Demographic, clinical,laboratory and endoscopic data were collected for each patient. Relapse rates and predictors for relapse were studied using survival and Cox regression analysis.

Results

A total of 52 IBD patients, mean age 50.8±14.7 years (46 UC and 6 CD), 25(48%) males, were included in the study. Mean follow-up was 29 months. 47.4% were treated with ADA and 51.5 % with IFX. The mean period of biologic therapy was 33.3 months for all patients. Upon treatment cessation, 55.8% of patients were in complete clinical remission, and 30.8% were in partial clinical remission.

Cumulative relapse rates at 6, 12, 24 and 36 months were 23.9%, 39.1%, 44.2% and 69.7% respectively for all UC patients while 66.7% of CD patients relapsed within 6 months. The mean time to relapse was 13 months for UC and 5 months for CD patients.

Among all IBD patients in complete clinical remission at the time of treatment discontinuation, the cumulative relapse rates at 6, 12, 24 and 36 months, were: 6.9%, 24.8%, 57.7%, and 58% respectively. Significantly higher cumulative relapse rates were found in patients with partial remission, the at the same time points: 37.5%, 50%, 75%, and 81.2% respectively (p=0.01).

Multivariable Cox analysis revealed that the only factor associated with lower risk of relapse was mucosal healing (vs nonmucosal healing: HR, 0.322; 95% CI, 1.26 to 6.677; p=0.012).

Conclusion

The majority of IBD patients relapsed within 3 years after anti TNFα discontinuation, Mucosal healing was the only factor associated with a lower risk of relapse. These results emphasise the crucial role of mucosal healing in guiding treatment decisions for IBD patients.
P744 Evaluation of a lifestyle program based on physical activity on quality of life and fatigue in patients with Inflammatory Bowel Disease: a pilot study
Authors: Van De Pol N , Visser E H , van der Woude C J , de Vries A C , de Jonge V , West R L
Published: January 2024

Background

Patients with inflammatory bowel disease (IBD) tend to be less physical active, whilst maintaining an active lifestyle has been associated with enhanced disease control, diminished fatigue and improved quality of life. The primary objective was to evaluate the potential impact on physical fitness, fatigue, quality of life and disease control of a specially designed exercise program for IBD patients.

Methods

Patients with IBD, treated at two teaching hospitals in the southwest of the Netherlands, participated in a 16-week exercise program (IBD-Fit) between March until June 2023. The program was designed especially for patients with IBD to sport with peers and was adjusted to a patient's fitness level. Improvement of physical fitness (measured with body composition, grip strength, sit-and-reach test, Y-balance test and 6-minute walk test) was analysed. In addition, patients were asked to fill in validated questionnaires at baseline and at the end of the program (IBD-Quality of life, IBD-Fatigue and IBD-control), to assess the effect of the exercise program on quality of life, fatigue and disease control. For statistical analyses, a paired t-test or Wilcoxon matched paired rank test was used.

Results

A total of 27/32 patients completed the entire exercise program, with a mean age of 50.4 years (SD 12.5), 40.7% were male, 48.1% had Crohn’s disease and 51.9% had ulcerative colitis (table 1). After 16 weeks, body composition, such as BMI and muscle mass improved compared to baseline; fat percentage significantly decreased (32.3 to 29.7%; Z=-2.983; P=0.003). Physical fitness improved significantly, based on the sit-and-reach test (23 to 29 cm; Z=-3.03; P=0.002), the absolute reach distance of the Y-balance test (73.7 to 79 cm; Z=-2.77; P=0.006), and the mean distance during a 6-minute walk test (505.2 to 557.5 m; 95%CI 32.6 – 72.2; P<0.001). Grip strength showed no significant improvement. Quality of life improved on average with 8.0 points on the IBDQ. The Systemic Symptoms domain improved significantly (mean difference 2.7; 95%CI 0.1–5.4, P=0.043). The program significantly improved fatigue scores (Z = -2.296, P=0.022). Disease control showed no significant improvement after the program. Overall, patients were very satisfied with the exercise program. Average rating was 8.6 out of 10.

Conclusion

This pilot study in a small number of patients shows that a specially designed exercise program has a positive effect on IBD patients. These results underline the importance to broaden our standard of care and can be used as a steppingstone to implement the program on a larger scale and ultimately become part of the standard of care for patients with IBD.
P745 Assessment of Crohn’s disease patients following risankizumab initiation using intestinal ultrasound: A prospective study
Authors: Rosentreter R , Ingram R , Ma C , Chan M , Shukla T , Devlin S , Kaplan G , Seow C , Panaccione R , Novak K , Lu C
Published: January 2024

Background

Risankizumab (RIS) is a humanized monoclonal antibody that inhibits interleukin-23 by binding to its p19 subunit. The use of RIS in the treatment of moderate to severe Crohn’s Disease (CD) was approved in December 2022. Intestinal ultrasound (IUS) is an accurate and well-tolerated modality for evaluating response to therapy. Here, we assessed the IUS response at 3 and 6 months following RIS therapy.

Methods

CD patients initiating RIS were recruited and evaluated by IUS at baseline (within 14 days of initiation), 3, and 6 months. Data elements collected at baseline included demographics, medication exposures, surgical history, as well as inflammatory biomarkers. IUS response (decrease in bowel wall thickness (BWT) ≥ 25%)) and transmural remission (TR) (normalization of BWT normalization, color doppler signal (CDS, modified Limberg (ML) score 0), wall stratification, inflammatory fat)) for each segment were evaluated. Paired t-tests were used to compare values at 3 and 6 months relative to baseline.

Results

A total of thirty-three (20, 60.6% female) patients were recruited; 30 completed baseline and 3 month IUS, while 18 patients have also completed a 6 month IUS. Median age was 55 years (IQR 39-63), with a 12 year median CD duration (IQR 5-28). Five had inflammatory behaviour, 19 had stricturing, and 6 had fistulizing behaviour. CD distribution was 18 ileal, 1 colonic, and 11 ileocolonic. Baseline mean CRP (4.1 ± 4.9 mg/L) did not differ at 3 months (5.0 ± 6.8 mg/L, p=0.16), nor at 6 months for patients with values available (6.2mg/L ± 8.3, p = 0.38). Of patients with FC concentrations, 3 month mean FC (129.4 ±70 mcg/g) (9 patients) had significantly decreased from baseline (427.6 ± 271 mcg/g) (p=0.008), and similarly at 6 months (9 patients; baseline 396 ± 299 vs. 129 ± 75, p = 0.02). 80.0% (4/5) patients with colonic BWT > 3mm had IUS response (baseline mean BWT 5.6±1.4mm vs 3.5 ± 0.8mm at 3 months (p=0.011). IUS response was achieved in 20% (5/25) with ileal CD at 3 months (BWT 6.3 ± 2.1mm vs 3 month 6.0 ± 2.5mm (p=0.31). 21.4% (3/14) of ileal CD patients had an IUS response at 6 months. There was a non-significant ileal BWT reduction (5.4 ± 1.6mm) from baseline (6.0 ± 1.7mm) at 6 months. Of the 9 with moderate to severe CDS, 55% (5/9) had reduction to mild CDS by 3 months. TR was achieved by one patient with ileal CD at 6 months.

Conclusion

IUS response was achieved in 80.0% of CD patients with colonic disease at 3 months follow RIS initiation. IUS response was detected for 20% of ileal CD patients at 3 months and 21.4% at 6 months A significant FC reduction by 3 and 6 months was attained. Further prospective patient recruitment and IUS at 6 and 12 months to assess preliminary results and longer-term response is needed.
P767 Pharmacokinetics of subcutaneous infliximab induction and maintenance in patients with moderate-to-severely active Crohn’s disease
Authors: Anjie S , Mâthot R A A , Gecse K B , D'Haens G R A M
Published: January 2024

Background

Since 2021, subcutaneous (SC) infliximab (IFX) has been available for maintenance treatment of Crohn’s disease (CD) after an induction phase of 2 intravenous administrations of 5 mg/kg. The DIRECT-CD study is an ongoing randomised multicentre trial in which CD patients receive SC IFX also during induction. The applied SC IFX doses in the DIRECT-CD are based on population pharmacokinetics derived during maintenance treatment with SC IFX. We aimed to validate our induction regimen and correlate serum concentrations with clinical efficacy.

Methods

Patients with moderate-to-severe CD (Crohn’s disease activity index [CDAI]) >220 and endoscopic ulceration) received fixed SC IFX induction doses of 240 mg at week 0 and 2, followed by maintenance treatment (120 mg every other week). IFX serum concentrations and CDAI were evaluated at week 2, 4, 8, 14 and 26. Clinical remission was defined as a CDAI ≤150. For this analysis, body weight is defined as low if <80 kg and high if ≥80 kg.

Results

In total, 48 samples of 12 Crohn’s disease patients were analysed (Table 1). During the induction phase (week 2 and 4), observed IFX serum concentrations were lower than expected by the population pharmacokinetic model for all patients (median 15.0 µg/mL [IQR 9.4-20.0]). Moreover, concentrations were significantly lower in patients with a low versus high body weight (median 20.0 µg/mL [IQR 15.0-21.0] vs median 10.2 µg/mL [IQR 4.4-15.8], resp., P=0.004). During the maintenance phase (week 8, 14 and 26), median IFX serum concentrations were also higher in patients with a low body weight compared to patients with a high body weight (17.5 µg/mL [IQR 14.8-19.5] vs 8.9 µg/mL [IQR 5.8-13.8], P<0.001). No patients in the first quartile of IFX serum concentrations (≤7.0 µg/mL) at week 2 reached clinical remission at Week 8, whereas all patients who had an IFX serum concentration at week 2 of ≥15.0 µg/mL reached clinical remission at week 8. At the end of the study (week 26), clinical remission was reached in 67% of patients with a low body weight whereas only 33% of patients with a high body weight reached clinical remission.

Conclusion

These data implicate the importance of body weight in SC IFX dosing strategies. Based on these findings, SC IFX induction and maintenance treatment is changed to a weight-based dosing scheme in the ongoing DIRECT-CD trial.
P787 Use of upadacitinib to treat IBD in post-liver transplant
Authors: Miyatani Y , Choi D , Choi N K , Aronsohn A I , Pillai A , Cohen R D , Rubin D T
Published: January 2024

Background

Approximately 2% of patients with inflammatory bowel disease (IBD) have concurrent primary sclerosing cholangitis (PSC). Liver transplantation (LT) is sometimes required due to progressive PSC. However, the management of active IBD post-LT is challenged due to concomitant anti-rejection immunotherapies. Janus kinase inhibition has been previously described to have anti-rejection properties in patients who have had renal transplants. Here, we describe our experience with upadacitinib (UPA), a selective Janus kinase-1 inhibitor, for post-LT active IBD combined with anti-rejection immunosuppression therapy.

Methods

This is a retrospective, single-center observational study in a tertiary IBD center. We identified patients with LT treated with UPA for their IBD. Patient related outcomes including transplanted liver status and clinical efficacy and safety of UPA for IBD activity were reviewed.

Results

We identified four patients (3 with Crohn’s disease, 1 with ulcerative colitis) treated with UPA after LT due to PSC, with the UPA indication for the treatment of IBD (n=3) and organ rejection (n=1). Median follow-up was 3 months (interquartile range (IQR) 1.5-7.1), median age at starting UPA was 41.5 years (IQR 40-44), and median interval from the transplant was 3.2 years (IQR 2.3-5.6). Two patients with Crohn’s disease clinically responded to UPA, one weaned off prednisone 30mg/day and remained in clinical remission after reducing UPA from 30 mg/day to 15 mg/day. Two patients developed elevated AST/ALT of up to 107/57 U/L and 83/228 U/L; one required discontinuation of UPA at one month with subsequent AST/ALT normalization; the other remained on UPA with 1.5 month follow-up so far. One UC patient was treated with UPA combined with vedolizumab in an attempt to discontinue prednisone for their immunosuppression for organ rejection, however, they were unable to wean off prednisone due to recurrent ALT and Alk Phos elevations. One patient acquired a mild case of COVID-19 which resolved without change in therapy. No life-threatening adverse events were observed.

Conclusion

We describe 4 patients with IBD who had LT for PSC and who were treated with UPA with successful management of active IBD in 2 cases but lack of efficacy in one case and liver enzyme elevations limiting UPA use in a second. These findings support further exploration of this novel mechanism for treatment of IBD in the post-LT setting.
P799 Deficits in geriatric assessment are dynamic over 18 months and impacted by therapeutic treatment in older patients with Inflammatory Bowel Disease
Authors: Fons A , Asscher V , Stuyt R , Baven-Pronk M , van der Marel S , Jacobs R , van der Meulen-de Jong A , Mooijaart S , Kalisvaart K , Maljaars J
Published: January 2024

Background

Frailty is a dynamic condition, however most previous studies in patients with IBD measured frailty at one point in time. Therefore, we aimed to study the course frailty, reflected by deficits measured in a geriatric assessment, during 18 months follow-up in older patients with Inflammatory Bowel Disease (IBD). In addition, we aimed to identify factors associated with changes in geriatric deficits over time.

Methods

In a prospective, multicenter cohort study, a geriatric assessment was performed at baseline and repeated after 18 months in 154 older patients with IBD. This geriatric assessment evaluated the presence of deficits in five geriatric domains: the somatic domain, mental domain, social domain, activities of daily living and physical capacity. The number and type of impaired domains at baseline were compared to follow-up. An increase in number of domains suggests worsening frailty, whereas a decrease in number of impaired domains suggests improving frailty. Logistic regression was performed to identify factors associated with change in number of domains. All analyses were adjusted for age, sex, type of IBD and educational level.

Results

During follow-up, 32.5% had increased and 26.0% decreased ≥ 1 in number of impaired domains, compared to baseline. At domain level, the proportion of patients with impaired activities of daily living decreased from 49.4% at baseline to 37.7% at follow-up (p-value=0.001). The proportion with impaired physical capacity increased from 14.3% to 26.0% (p-value=0.001). Use of systemic corticosteroid at baseline and/or the year prior to baseline was associated with an increase in impaired domains (aOR 3.00; 95% confidence interval (95% CI) 1.11-8.08; p-value= 0.030), while initiation of biological therapy was associated with a decrease in impaired domains at follow-up compared to baseline (aOR 4.92, 95%CI 1.41-17.15, p-value=0.013).

Conclusion

Geriatric deficits, reflecting levels of frailty, are dynamic over 18 months in older patients with IBD. Therapeutic IBD management appeared an important determinant for the longitudinal course of frailty. This study provides the first longitudinal data on the course of geriatric deficits, measured in a geriatric assessment, in older patients with IBD.
P805 The persistence of subcutaneous infliximab is equivalent to intravenous form in patients with inflammatory bowel diseases
Authors: Bothorel L , Laharie D , Poullenot F , Gohier E , Chevrier C , Berger A , Zerbib F , Riviere P
Published: January 2024

Background

Switching from intravenous (IV) infliximab to subcutaneous (SC) is a new tool in treating patients with inflammatory bowel disease (IBD). This study aimed to evaluate the persistence and tolerance of SC IFX compared to IV IFX and to study outcomes of patients switched back to IV in a real-life patient cohort.

Methods

We conducted a retrospective monocentric study involving consecutive patients with IBD treated with maintenance IV IFX. The switch to SC was offered to patients in clinical remission receiving an IFX IV dose ≤ 10mg/kg every ≥ 6 weeks, and with a favorable patient profile (good adherence to IFX IV treatment, no decompensated psychiatric condition). Two groups were compared: a "switched" group receiving SC and a control group remaining on IV IFX due to an unfavorable patient profile or refusal of the switch.

Results

Among 360 consecutive patients treated by IV IFX, 282 were switched to SC and 78 remained on IV (44 due to refusal and 34 with an unfavorable profile). Both groups were similar in age, sex, and disease type and location; IV IFX dosage and frequency were higher in the IV group.

With a median follow-up of 59 (46-67) weeks, SC IFX was discontinued in 28/282 (10%) patients (10 due to relapse, 10 by patient decision, and 8 due to intolerance), whereas it was stopped in 1/78 (1%) IV IFX patient for intolerance (p=0.01). Among the 28 who discontinued SC IFX, 27 reverted to IV, with 4 (1% of the switch group) permanently stopping IFX. Overall, persistence rates for IFX, irrespective of administration route, were comparable between the two groups at 52 weeks: 99% (96-100%) for IV versus 99% (98-100%) for SC (p=0.60). Adverse events were more frequent in the switched group than the control group (10% versus 3%, p=0.03). Primarily, this involved psoriasiform lesions in 9 patients; 4 patients reported an injection site reaction. The proportion of side effects leading to IFX discontinuation or hospitalization was identical in both groups (1 patient, 2%).

Conclusion

In a real-life cohort, switching from IV to SC IFX does not alter treatment persistence. In cases of poor tolerance to SC IFX, IV IFX re-initiation is effective. Switching to SC IFX is a therapeutic option for patients in remission on IV IFX.
P807 HLA type impact on immunization and efficacy of ustekinumab in IBD patients: a multicenter study
Authors: Delmeule A , Dubois V , gay C , Roblin X , Paul S , Nancey S , Boschetti G
Published: January 2024

Background

About 30% of patients treated with ustekinumab will present primary or secondary failure. Outcomes and frequency of ustekinumab immunization are still controversial. Some HLA types (especially DQA1*05) appear to be predictive factors of anti TNFα immunization. This study aimed to assess the impact of HLA type on the risk of immunization and on the efficacy of ustekinumab.

Methods

IBD patients treatede with ustekinumab in Saint-Etienne and Lyon hospitals were included between 2017 and 2023. Ustekinulab through level was measured by ELISA and HLA type (DQA1, DQB1, DRB1) determined by PCR. Anti-drug antibodies (ADA) detection was done using both a "drug sensitive" assay (ELISA) and an innovative "drug tolerant" method based on anti human lambda chain. Data about clinical, biological (CRP, fecal calprotectin) and endoscopic responses were retrospectively collected.

Results

Among the 115 patients included (43% males, mean age of 40 years old), 98 had Crohn disease. Nighty-eight percent of the patients were previously treated with at least one anti-TNFα and 33% of them were immunized. In this study, 43 patients were immunized against ustekinumab with the "drug tolerant" assay and only 2 with the "drug sensitive" method. Immunization tended to reduce (not significatively) clinical, biological and endoscopic responses. Ustekinumab through level was significately higher for patients with good clinical (p = 0.009) and biological (p = 0.036). HLA DQA1*05 or DRB1*03 carriage was associated with higher risk of immunization (OR = 5.13, p = 0.048 / OR = 5.36, p = 0.006) and with a trend to decrease clinico-biological response. Other HLA types, notable DQA1*01 tended to be associated with a lower immunization (OR = 0.7, p=0.3) and a better response (OR = 2.55, p = 0.018). A small group involved (26 patients), combination therapy at induction had no significant benefit in terms of immunization prevention or therapeutic response. Sub-groups analysis seemed to confirm some HLA types involvement, by breaking free of imbalances due to haplotype transmission.

Conclusion

Our study suggests the usefulness of ustekinumab monitoring and a more common immunization than previously described. HLA type seem to influence immunization and ustekinumab response. Some specific HLA types and patients profiles tend to be associated with a higher risk of immunization not only to anti-TNFα but also to ustekinumab.
P814 Empowering IBD communities worldwide: The global impact of www.ibd-eii.com in disseminating evidence-based information and educational support
Authors: Gros B
Published: January 2024

Background

In recent decades, the volume of inflammatory bowel disease (IBD) research has surged, presenting a challenge for health care professionals to be updated. This is even more complicated for professionals in countries with low IBD prevalence and for registrars, fellows and other healthcare professionals.

Methods

IBD-EII website was launched the 8th February 2023 and serves as a comprehensive, unfunded and free platform offering up-to-date IBD evidence-based data. To highlight the impact, analyzing its first 8 months (data extracted via Google Analytics as of October 26, 2023) and using a google form questionnaire that was sent to subscribers in August 2023.

Results

The website encompasses over 300 trials and study summaries, along with 22 evidence-corner summaries, 102 guidelines from 12 scientific societies, 19 infographics featuring classifications and scores, 65 Cochrane meta-analyses and 13 network meta-analysis.

Over the study period, there were 151,736 visits from 139 countries, with an average of 8.29 visits per user. The top-engaged countries were the United States, United Kingdom, Spain, Russia, and India (Figure 1). The site garnered 1058 subscriptions, with 10 (0.9%) individuals unsubscribing during the study period.

Of the 850 invited users, 81 (9.5%) filled the questionnaire. Of them 53 (65.4%) were female. There were 49 (60.5%) healthcare professionals, 35 (43.2%) patients/family members of a patient, 4 (6%) were IBD researchers/ pharma industry workers, working for patients organization or both doctor and patient. Among healthcare professionals, 22 (44%) were IBD specialists, 14 (28%) general gastroenterologists, 4 (8%) trainees/ med school, 12 (24%) were IBD nurses/dieticians or pharmacists, 3 (6%) others. Most people have heard of the website in social media 66 (81.5%), by colleagues recommendation 8 (9.9%), congresses 7 (8.6%), or other 5 (6%). Website impact: 80 (98.8%) thought it was useful, 80 (98.8%) recommended to be subscribed. The most valuable sections were "evidence corner" 56 (69.1%) followed by guidelines 48 (59.3%) and timeline 35 (43.2%).

Conclusion

The data highlights the significant global impact of www.ibd-eii.com in disseminating evidence-based information to a diverse international community of healthcare professionals and patients. The website stands as a novel resource, fostering collaboration and empowerment within the global IBD community.
P828 Evaluation of adherence and beliefs about medication in patients with Inflammatory Bowel Disease following a novel microlearning programme (The ADEII project)
Authors: De Castro Parga M L , Hernández V , Sanromán L , Figueira M , Martínez-Cadilla J , Rodriguez-Prada I
Published: January 2024

Background

Information and communication technologies (ICTs) represent a novel approach to chronic disease management. However, their use in Inflammatory Bowel Disease (IBD) is lacking and their results as far unknown, because no specific tools are available. The rate of non-adherence in IBD ranges from 30 to 40%, with medication concerns being one of the main factors. Our aim was to evaluate the outcomes of a novel microlearning programme for IBD patients in adherence and beliefs about medication.

Methods

Prospective cohort study in adult patients with IBD (18 to 70 years old) who underwent a microlearning programme over a 2-month period, throught 4-minute videos organised in individualised video pathways that were sent via mobile phone using a Telegram bot. All patients received the 4-video main pack, consisting of 2 videos with information about their disease (ulcerative colitis or Crohn's disease), 1 video on adherence and another one on steroid treatment. To these were added as many videos as the number of drugs used by the patient to control IBD. Before starting the programme and at 6 months, patients completed the Medicines Beliefs Questionnaire (BMQ). Adherence was defined as a medication possession ratio (MPR≥80%) at these same dates. MPR values were computed separately for each drug, and patients on combination therapy were considered adherents if they got MPR≥0.8 in every prescribed medication.

Results

Between 1 June and 31 October 2022, 1226 videos were sent to 200 IBD patients: 51.5% female (103), UC 52.5% (105), mean age 46.1 (13.2) years (Table 1). Median number of videos per patient was 6 (6-7). Attendance to ADEII programme ranged between 78% and 90%. Prior to the study, Initial non-adherence was 29.8% (59 patients), decreasing significatively to 18.1% (36) after the programme (p=0.02). Regarding BMQ test, we also found significant differences between the pre-intervention versus post-intervention medians and IQR of General BMQ score 18 (15 -21,8) vs. 17 (13.3 - 20) (p=0,001), BMQ-Overuse score 8 (7 -9) vs. 8 (6 -9) (p=0,027), BMQ-Harm score 10 (8 -12) vs 9.5 (7-11) (p=0,002) and BMQ-Concern score 13,5 ( 11-16) vs 13 (10-16) (p=0,001), with no changes in BMQ Global Specific and BMQ-Necessity scores.

Conclusion

Patients with IBD widely accepted an ICT-based educational program, which improved adherence, along with a decrease in negative ideas or beliefs about medications.