bluuebunny/crossref_metadata_2025 huggingface dataset:
P610 Ustekinumab demonstrates superior treatment persistence over anti-TNF in Crohn’s disease patients previously treated with vedolizumab
Authors: Chiu H Y , Le P H , Yeh P J , Kuo C J , Lai M , Wu R C , Chen C M , Chiu C T , Chiu C H , Su M , Pan Y B
Published: January 2024

Background

With the rise in biologic therapies to manage moderate to severe inflammatory bowel disease (IBD), determining the optimal treatment sequence has become crucial. This aids in the selection of the next biologic agent after prior exposure or unresponsiveness to a previous regimen. Vedolizumab (VDZ) is a gut-specific α4β7-integrin inhibitor recognized for its efficacy in treating moderate to severe IBD. Yet, only a few studies have assessed the comparative effectiveness of alternative biologics, such as ustekinumab (UST) and antitumor necrosis factor agents (anti-TNF), following VDZ exposure.

Methods

In our retrospective study conducted at Chang Gung Memorial Hospital at Linkou, a leading 3700-bed medical facility in Taiwan, we examined 110 IBD patients who underwent treatment with UST or anti-TNF agents (including adalimumab and infliximab) from May 2019 to September 2023. UST's standard maintenance dosing in Taiwan is every 12 weeks. We utilized Kaplan-Meier analysis and Cox proportional hazards models to evaluate the 52-week treatment retention of UST versus anti-TNF.

Results

Of the 110 participants, 40 were diagnosed with ulcerative colitis (UC), and 70 with Crohn’s disease. The demographics between the anti-TNF and UST groups regarding age, gender, and body mass index were comparable. The primary reason for vedolizumab discontinuation in both groups was secondary non-response (Table 1). UST exhibited a notably higher 52-week retention in overall IBD (HR: 5.36, 95% CI: 1.84-15.62, P = 0.002, Figure 1a) and in Crohn’s disease patients (HR: 10.75, 95% CI: 1.34-86, P = 0.025, Figure 1b) compared to anti-TNF. While UST also showed superior persistence at 52 weeks in UC patients, the difference was not statistically significant (HR: 2.25, 95% CI: 0.63-8, P = 0.211, Figure 1c). At the 52-week mark, 73.5% of the anti-TNF group and 81% of the UST group were not on steroids. Secondary non-response was the predominant cause for discontinuation of the current biologic. Notably, UST required more frequent dose adjustments than anti-TNF. The safety profile of both treatments was comparable.

Conclusion

UST showed superior treatment persistence, compared to anti-TNF in Crohn's disease patients who had previously been exposed to vedolizumab. However, UST required more frequent dosing adjustments compared to anti-TNF.
P683 Economic impact of achieving mucosal healing on UC-related hospitalisations and work productivity in patients with moderately to severely active UC: A post-hoc analysis of risankizumab Phase 2b/3 trials
Authors: Peyrin-Biroulet L , Ungaro R , Rubin D T , Bokemeyer B , Ricart E , Levine P , Lai J H , Sharma D , Vladea R , Sanchez Gonzalez Y , Patel K
Published: January 2024

Background

The value of endoscopic-histologic healing is incompletely understood, and definitions are variable. We assessed the clinical and economic value of achieving mucosal healing in patients with ulcerative colitis (UC) by evaluating the relationship of histologic-endoscopic mucosal improvement (HEMI) and subsequent UC-related hospitalisation and work productivity, and associated costs in the United States (US); United Kingdom (UK); and France, Germany, Italy, and Spain (EU4).

Methods

Data from the risankizumab (RZB) INSPIRE induction (NCT03398148) and COMMAND maintenance (NCT03398135) studies were analysed. The number of UC-related hospitalisations was compared in patients who achieved HEMI or no HEMI using a chi-square test. The mean percent changes in Work Productivity and Activity Impairment (WPAI)-UC domains from baseline to induction week 12 and maintenance week 52 were compared in patients who achieved HEMI or no HEMI using analysis of variance test. Hospitalisation and work productivity differences during induction and maintenance were converted to annualised costs based on average earnings and hospitalisation cost inputs from US, UK, and EU4.

Results

UC-related hospitalisations were significantly lower in patients who achieved HEMI at induction week 12 than those who did not (0% vs 2.9%, p≤0.05). A similar result was found at maintenance week 52, but the difference was not significant. In patients who achieved HEMI vs no HEMI, a greater mean change in activity impairment, impairment while working, and overall work impairment from baseline to induction week 12 was observed (p≤0.001). Improvements were sustained at maintenance week 52 for patients who achieved HEMI vs those who did not. Estimated annualised cost benefits from maintenance data for UC-related hospitalisations in patients who achieved HEMI was $490 in the US, £29 in the UK, and €28–€58 in EU4. Greater monetised benefits accrued from work productivity gains, where estimated annualised cost savings were $5,085 in the US, £3,507 in the UK, and €3,240–€4,456 in EU4.

Conclusion

These findings demonstrate that patients treated with RZB who achieved HEMI had fewer UC-related hospitalisations and greater improvement in work productivity and ability to perform daily activities than those who did not, which results in moderate direct cost savings and substantial indirect cost savings to healthcare systems in the US, UK, and EU4.
P775 Efficacy and safety of risankizumab in children with Crohn’s disease: A preliminary report
Authors: Spencer E , Stein R , Shalem T , Zifman E , Dubinsky M , Lev Tzion R , Turner D , Assa A
Published: January 2024

Background

Risankizumab (RISA) is a selective p19 anti-interleukin (IL)-23 antibody approved for adults with Crohn’s disease (CD) and for children ≥ 16 years in selected countries. Given delays in pediatric approvals, we aimed to assess the real-world effectiveness and safety of RISA in pediatric patients with CD.

Methods

From September 2022 to November 2023, all pediatric patients (<18 years) with refractory CD treated with RISA in 5 centers from US and Israel were retrospectively included. All received a 600 mg RISA intravenous induction at weeks 0-4-8. Patients completing the induction phase were treated with subcutaneous injection of 360mg at week 12 and every 8 weeks thereafter. The primary endpoint was steroid-free clinical remission (SFR) after 3 intravenous infusions (i.e., wPCDAI ≤12.5). Secondary endpoints included clinical response (i.e., >17.5-point decrease of wPCDAI), biochemical remission (CRP ≤ 5 mg/L) and drug sustainability. Adverse events were explicitly recorded.

Results

Included were 23 children [13 (56%) males; mean age at diagnosis 14.1±3.7 years, median disease duration 3.9 (IQR 2.6-7.7) years, 11 (48%) < 16 years of age] with a median follow-up period of 21 weeks (IQR 9.4-44.2) (Table 1). All had failed at least one previous biologic treatment and 18 (78%) failed two, including 15 (65%) with prior ustekinumab treatment. After 3 infusions, SFR was observed in 15 (65%) children, clinical remission in 16 (70%), clinical response in 17 (74%), and CRP remission in 17 (74%). There was no difference in response rate of patients <16 years (64% SFR). In a subgroup analysis of 15 patients with prior ustekinumab exposure, SFR was observed in 11 (73%). Only two patients discontinued RISA during follow-up, one who was in clinical and CRP remission at week 12, due to loss of follow-up and the other due to occurrence of an intra-abdominal abscess. Ten patients completed 6 months follow-up, of whom 8 (80%) achieved SFR by then. Only one disease-related adverse event occurred in one patient (intra-abdominal abscess). No drug-related adverse events were recorded.

Conclusion

While awaiting pediatric registration trials, our preliminary data suggest that RISA is safe and effective in inducing and maintaining remission in children with highly-refractory CD. This includes also children previously failing ustekinumab and children younger than 16 years.
P812 Whole Food and Antioxidants Consumption Linked to Lower Risk of Inflammatory Bowel Disease in Taiwan
Authors: Meng M J , Huang J , Le P H , Pan Y B , Chiu C T , Lin Y T
Published: January 2024

Background

The incidence of inflammatory bowel disease (IBD) rapidly increases in Asia, and western dietary pattern is suspected to be the major risk factor. Despite this, there has been a lack of studies analyzing the relationship between dietary patterns and IBD in Taiwan. This study examines the dietary habits of Taiwanese individuals with and without IBD to inform clinical dietary recommendations for IBD patients.

Methods

A comprehensive survey utilizing structured questionnaires to collect baseline characteristics and dietary information from both IBD patients and healthy controls from February and August 2022. The dietary habits of IBD patients in this study were focused on the three months leading up to their IBD diagnosis. Numerical data were presented as mean ± standard deviation, while categorical data were expressed as absolute numbers and percentages. Statistical analysis involved the Mann–Whitney U test for continuous variables and the chi-square or Fisher's exact test for categorical data. Statistical significance was defined as p < 0.05, and all analyses were performed using SPSS version 22.0.

Results

Our study included 98 IBD patients, with 46 diagnosed with Crohn's disease and 52 with ulcerative colitis, along with 184 healthy controls. Notably, in terms of baseline characteristics, the IBD group exhibited a significantly higher prevalence of cigarette smokers compared to the control group (29.5% vs. 12.6%, p = 0.001). Regarding dietary habits, IBD patients reported consuming significantly fewer natural food categories compared to the control group. These differences included lower consumption of rice products (p = 0.005), cereal products (p < 0.001), mixed-grain products (p < 0.001), mushrooms (p = 0.004), burdock (p = 0.001), poultry (p = 0.049), and milk (p < 0.001). Intake of red meat, seafood, and nuts was comparable. Concerning processed food products, IBD patients also reported less frequent consumption of soymilk (p = 0.017), mock meat (p = 0.012), and tea (p = 0.043). In terms of dietary supplements, IBD patients were less likely to use vitamin supplements (C or E) compared to healthy controls (25% vs. 42.4%, p = 0.004), and they also reported lower consumption of soybean lecithin (1% vs. 7.6%, p = 0.02). The baseline characteristics, frequency of natural foods, processed foods and dietary supplement consumption were summarized in Table 1.

Conclusion

The findings of our study suggest that a diet rich in whole foods and antioxidant may be associated with lower risk of IBD in Taiwan. However, it’s important to note that further research with a larger sample size is necessary to confirm these observations and provide more robust insights into the relationship between dietary factors and IBD.
P816 Baseline disease severity of patients with Ulcerative Colitis influences rapid symptom relief under filgotinib treatment: post hoc analysis of the phase 2b/3 SELECTION study
Authors: Saruta M , Danese S , Takatori Y , Kaise T , Rudolph C , Ferrante M , Hibi T
Published: January 2024

Background

Filgotinib (FIL) is an oral, once-daily, Janus kinase 1 preferential inhibitor approved in Europe and Japan for the treatment of ulcerative colitis (UC). A recent analysis of SELECTION trial data (NCT02914522) showed rapid and sustained improvements in UC symptoms with FIL 200 mg (FIL200) treatment in patients with moderate-to-severe UC.1 Here we assess symptomatic remission rates over time with FIL200 induction treatment according to baseline UC disease severity (partial Mayo Clinic Score [pMCS]).

Methods

SELECTION was a phase 2b/3 randomized, double-blind, placebo-controlled study. Patients aged 18–75 years were randomized (2:2:1) to receive FIL200, FIL 100 mg or placebo once daily for 11 weeks in induction study A (biologic-naive patients) or induction study B (biologic-experienced patients). In this post hoc analysis, proportions of patients with symptomatic remission (Mayo rectal bleeding sub-score of 0 and Mayo stool frequency sub-score of ≤ 1), from days 2 to 15 and weeks 2 to 10 of the induction study, were analysed at each timepoint by baseline pMCS (pMCS ≥7 and pMCS <7 [cut-off previously used for severe and moderate disease, respectively]2). Symptomatic remission rates were compared between the pMCS ≥7 and pMCS <7 groups within the FIL200 and placebo arms using a Cochran–Mantel–Haenszel test adjusted by study randomization stratification factors. Nominal p values <0.05 were considered statistically significant.

Results

At day 2, symptomatic remission rates with FIL200 treatment were significantly higher in patients with baseline pMCS <7 than in those with baseline pMCS ≥7 (8.4% vs 1.1%, p=0.009 [induction study A]; 8.8% vs 0.7%, p=0.004 [induction study B]) (Figure A and B). From days 2 to 15, symptomatic remission rates increased in both groups and, except for day 7 for induction study A and day 9 for induction study B, continued to be significantly higher in those with baseline pMCS <7. From week 2, symptomatic remission rates with FIL200 treatment generally continued to increase in both pMCS ≥7 and pMCS <7 groups (Figure C and D). By week 10, symptomatic remission rates with FIL200 treatment were no longer significantly different between those with baseline pMCS <7 and those with baseline pMCS ≥7 (54.8% vs 43.3%, p=0.124 [induction study A]; 39.5% vs 26.4%, p=0.099 [induction study B]).

Conclusion

Symptomatic response to FIL200 occurs more rapidly in patients with lower UC disease severity than in those with higher UC disease severity. However, converging response rates over 10 weeks of treatment leads to symptomatic remission regardless of baseline UC disease severity.

References

1. Danese S et al. Am J Gastroenterol 2023;118(1):138–47

2. Panés J et al. J Crohns Colitis 2019;13:1148–57
P823 Real-world effectiveness of upadacitinib in Crohn's disease; a UK multicentre retrospective cohort study
Authors: Elford A , Bishara M , Plevris N , Gros B , Constantine-Cooke N , Goodhand J , Kennedy N , Ahmad T , Lees C
Published: January 2024

Background

Upadacitinib is a Janus kinase inhibitor which has recently been approved for the treatment of Crohn’s disease. There are limited real-world studies on the outcomes of upadacitinib in Crohn’s disease. Our aim was to evaluate the outcomes of upadacitinib in a real-world cohort.

Methods

We conducted a retrospective, multicentre, cohort study. Our primary outcome was treatment persistence at week 24. Our secondary endpoints were corticosteroid-free clinical remission (Harvey-Bradshaw Index ≤4), and biomarker remission (CRP ≤5 mg/L and FCAL <250 µg/g). We measured outcomes at 12 weeks, 24 weeks and at last observation. We recorded adverse events.

Results

We included 74 patients who commenced upadacitinib over a two-year period for analysis, with a median follow-up time of 23 weeks (IQR, 15-39 weeks). All patients had failed anti-TNF therapy, with 78% and 58% additionally failing prior IL12/23 and vedolizumab (Table 1). Treatment persistence was 83.6% at week 12, and 76.6% at week 24 (Figure 1). Reasons for treatment cessation included primary non-response 15% (11/74), secondary loss of response 1% (1/74), and adverse events 12% (9/74). Rates of clinical remission were 58% (32/55) at week 12, 43% (16/37) at week 24, and 52% (35/67) at last observation. CRP remission rates were 45% (27/60) at week 12, 35% (12/34) at week 24, and 44% (30/69) at last observation. FCAL remission rates were 40% (17/42) at week 12, 31% (9/29) at week 24, and 36% (19/53), at last observation. There was a significant reduction in HBI, CRP and FCAL during follow-up (Figure 1). During the maintenance period, 11% (7/61) of the cohort who continued therapy were prescribed corticosteroids. Ten patients (19%) had a hospitalisation due to a Crohn’s flare. Five patients (7%) underwent Crohn’s disease related resectional surgery during the study period. Two were emergency surgeries (3%), and three (4%) were elective surgeries for symptomatic fibrotic strictures, which were present prior to commencing upadacitinib. Thirty-four adverse events were recorded across 29 patients (39%). Serious adverse events occurred in 9 patients (12%), three of which (4%) led to hospitalisation.

Conclusion

Upadacitinib was effective in a real-world, medically refractory, moderate to severe Crohn’s disease cohort with good persistence.
P825 Comprehensive dietitian-delivered dietary advice effectively achieves dietary change in adults with Ulcerative Colitis, whereas generalised written dietary advice does not
Authors: Portmann L , Bryant R , Raja S , Rayner C , Telfer K , Costello S , Day A
Published: January 2024

Background

Diet is an important consideration in microbial therapy trials. It is unclear whether provision of generalised written dietary advice is sufficient to induce dietary change as part of a therapeutic regimen or whether personalised diet advice is required. This study examines the effectiveness of different dietary advice modes provided in dietary and faecal microbiota transplantation (FMT) studies in adults with mild-moderately active ulcerative colitis (UC).

Methods

This observational study examined before and after dietary intake data from three prospective dietary and FMT studies held from 2018 to 2021 at a South Australian tertiary inflammatory bowel disease service. In all studies, adults ≥18 years with mild-moderately active UC completed 3 or 7-day weighed food diaries measuring habitual diet at 0 and 8 weeks after provision of dietitian-developed dietary advice. In studies one and two, a medical officer provided participants a written UC healthy eating pamphlet. The pamphlet contained generalised dietary recommendations for UC, targeting reduction of total and animal protein and increasing fermentable fibres including resistant starch to recommended serve sizes. In study three, a research dietitian provided a 1-week guided meal plan, diet manual with recipes and verbal personalised dietary counselling advising on the same recommendations and strategies. In all studies, participants were encouraged to eat to appetite. Dietary intake, including key nutrients of interest (protein and fermentable fibres), at weeks 0 and 8 was assessed using Foodworks 10TM nutritional analysis software and analysed using paired statistical tests.

Results

Across studies one and two, 28 adults with mild-moderately active UC received written dietary advice. In study three, 30 adults received personalised verbal and written dietary advice. Outlined in Table 1, verbal and written advice significantly reduced total protein and animal protein intakes by 20% (p=0.007) and 34% (p=0.002) respectively. Total fibre and resistant starch intakes significantly increased by 64% (p<0.001) and 353% (p<0.001) respectively. Comparatively, written advice alone had no significant change on any key nutrient intakes. Neither dietary advice mode significantly changed energy or micronutrient intakes.

Conclusion

Written dietary advice alone was insufficient to achieve dietary change. In contrast, verbal and written dietary advice with the same intended change on dietary intake, delivered by a research dietitian effectively achieved dietary changes. This emphasises that comprehensive written and verbal dietary education delivered by a dietitian should be included in microbial-modulating study designs where dietary change is an intended outcome.
P846 Impact of 5-ASA discontinuation in children with ulcerative colitis under biological therapy
Authors: D'Arcangelo G , Di Bari E R , Distante M , Rotulo S , Brecciaroli M , Catassi G , Aloi M
Published: January 2024

Background

Mesalamine (5-ASA) is recommended as a first-line medication for inducing and maintaining remission in mild to moderate ulcerative colitis (UC), but indications regarding its use in children with moderate to severe disease treated with biologics are lacking. We aimed to evaluate whether discontinuing 5-ASA might impact the outcomes of children with UC treated with anti-TNFα.

Methods

Retrospective, single-center, case-control study of children with UC receiving anti-TNFα therapy between January 2018 and January 2023 and with a minimum follow of 6 months. Children who discontinued 5-ASA within six months from the biological therapy initiation were compared to those who continued mesalamine as maintenance therapy. Every 6 months, during a 2-year follow-up, major outcomes defined as disease flares, IBD-related hospitalization, surgery, need for step-up treatment were recorded.

Results

Ninety-eight children were included in the final analysis, 51 (52%) maintained 5-ASA and 47 (48%) discontinued 5-ASA. The 2 groups were comparable for all the baseline clinical and demographic characteristics. At 6 months, the cumulative incidence of major outcomes, acute severe colitis and need for step up treatment was significantly higher in children who discontinued 5-ASA (p < 0.05). Throughout the follow-up period, children who discontinued 5-ASA were at significant higher risk of hospitalization (Log Rank p=0.02), need for step up treatment (Log Rank p=0.02) and acute severe colitis (Log Rank p=0.003).

Conclusion

Our data suggest that 5-ASA discontinuation might have a negative impact on the clinical course of children with UC treated with anti-TNFα in terms of major outcomes. However, conclusive evidence regarding this matter requires prospective randomized trials.
P850 Symptomatic effectiveness of ozanimod in routine clinical care of ulcerative colitis: an interim analysis of the multicentre, prospective, noninterventional COLIBRI study
Authors: Schubert S , Stein J , Efken P , Helwig U , Schulze J , Hellms T , Jorgensen E , Poehler A M , Scheibner F , Makki M , Zeissig S
Published: January 2024

Background

Ozanimod (OZA) is approved for the treatment of adults with moderately to severely active (MOD/SEV) ulcerative colitis (UC) per results of the phase 3 True North trial. Real-world data are needed to determine treatment effects in a more diverse population in clinical practice. The COLIBRI study (NCT05382715) assesses the use, effectiveness, and safety of OZA and quality of life in patients (pts) with MOD/SEV UC in a routine clinical practice setting in Germany over a period of 52 or 104 weeks. This interim analysis of COLIBRI reports baseline (BL) characteristics and evaluates the symptomatic clinical effectiveness of OZA up to Week (W) 10.

Methods

COLIBRI will enrol up to 380 adults with UC; the study design is shown in the Figure. Adherence to the times of visits and the diagnostic and therapeutic measures are not mandatory and will correspond to the routine processes of the respective facilities. Partial Mayo score (pMS; sum of stool frequency subscore [SFS], rectal bleeding subscore [RBS], and Physician Global Assessment), symptomatic clinical improvement, defined as either symptomatic response (decrease from BL in the combined 6-point SFS + RBS of ≥1 point and >30%, and decrease of ≥1 point in RBS or absolute RBS of ≤1 point) or symptomatic remission (RBS = 0 and SFS ≤1, and a decrease of ≥1 point from BL SFS), and symptomatic remission were assessed at W4 and W10. Data were collected by electronic case report forms and by the study-specific interface of the MyTARGET app (Kiel, Germany) for pt-related outcomes, which were evaluated throughout the study.

Results

Of 83 pts included in this interim analysis (BL and W4, n=58; BL and W10, n=39), the median (interquartile range) age of pts was 40 (29.0–53.0) years, 49 (59.0%) were female and 34 (41.0%) male, 80.7% had prior exposure to advanced therapies (AT), and 48.2% had prior exposure to ≥3 AT. Overall, 67.5% had prior tumor necrosis factor alpha inhibitor and 50.6% had prior vedolizumab use. BL pt characteristics are shown in the Table. In total, 76 pts with BL data had pMS data; the mean (SD) pMS at BL was 5.0 (2.2), and most pts fell within the moderate pMS category (44.9%). Mean (SD) pMS decreased from BL (5.0 [2.2]) to 3.9 (2.6) at W4 and to 3.5 (2.3) at W10. Symptomatic clinical improvement was achieved in 32.8% (19/58) and 51.3% (20/39) of pts at W4 and W10, respectively. Symptomatic remission was achieved in 22.4% (13/58) and 25.6% (10/39) of pts at W4 and W10, respectively.

Conclusion

This interim analysis of the German COLIBRI study showed that refractory pts with MOD/SEV UC receiving OZA achieved symptomatic effectiveness at W4 and W10 in a routine clinical practice setting.
P859 Sodium Butyrate supplementation significantly improved clinical outcomes and quality of life in patients with Crohn’s Disease – results from a randomized placebo-controlled study
Authors: Facchin S , Calgaro M , Pandolfo M , De Barba C , Barberio B , Zingone F , Vitulo N , Savarino E V
Published: January 2024

Background

Butyrate has shown anti-inflammatory effects and plays an important role in maintaining gut homeostasis, providing symptomatic relief when orally supplemented in patients suffering from various colonic diseases.

Methods

In this randomised, double-blind, placebo-controlled study 140 IBD patients in remission or with mild disease (n=60 Crohn's disease, CD and n=80 Ulcerative Colitis, UC) were randomized to oral administration of BLM/placebo for 90 days in addition to conventional therapy. As primary aim: changes in microbiome composition induced by BLM treatment. Fecal microbiota from stool samples was assessed by 16S sequencing. Clinical disease activity assessed by using Harvey Bradshaw Index (HBI) for CD and partial-Mayo Score (pMS) for UC, quality of life assessed by using Inflammatory Bowel Disease Questionnaire 32 (IBDQ-32) and adherence-dietary-raccomandation( WCRF) were evaluated before and after treatment.

Results

Demographics, clinical and dietary characteristics were similar between the two populations. The microbiota sequencing highlighted two different enterotypes in CD population: the first one was characterized by a low F/B ratio (with a genus prevalence of Fusobacteriota, Alistipes, and Blautia). The second enterotype was characterized by a higher F/B ratio (with a genus prevalence of Escherichia-Shigella and Lachnoclostridium)(Fig1). BLM had a more pronounced effect on enterotype-1 where the taxa associated with intestinal comfort, SCFA production, increased after treatment, while the taxa associated with CRC and intestinal inflammation, decreased. After treatment was observed: a)improved quality of life (IBDQ-32: CD: treat. 170/184 vs Pb. 188/197 p<0.001 vs p=0.021; UC: treat.185/195 vs Pb.188/188 p=0.003 vs p=0.4), b)lower disease activity in CD patients (the HBI score, showed a significant improvement for those treated with BLM as compared to placebo (McNemar’s p=0.013 vs p>0.9).c) reduced Calprotectin levels (Table1.) Finally, a significant separation was observed in samples from patients who have undergone minor surgery (ileo-colon), compared to non-surgery patients. The variable "surgery" seems to be associated with the enterotype-1.

Conclusion

Sodium butyrate supplementation significantly improved clinical outcomes and quality of life in patients with CD. Our data showed that the differential response to BLM treatment is based on enterotype, suggesting that Enterotype-1 patients may experience greater clinical benefits and improvements in QoL compared to Enterotype-2 patients in both UC and CD populations.
P870 Effectiveness and safety of adalimumab as first line biological treatment in Ulcerative Colitis
Authors: López Cardona J , Sharma E , Lal N , Anderson S , Dart R , Mawdsley J , Ray S , Samaan M , Irving P
Published: January 2024

Background

The increase in licensed therapies for ulcerative colitis (UC) is revolutionizing its treatment but making first line choice more challenging. Adalimumab (ADA) is inexpensive but, anecdotally, is sometimes regarded as less effective than other first line advanced therapies. We aimed to evaluate the results of first line ADA in UC.

Methods

We performed a single centre retrospective analysis of UC patients started on ADA between January 15 and March 2022 in an IBD referral hospital. Clinical remission was defined as SCCAI <2 points, endoscopic remission as a UCEIS <2 points and treatment failure as the need for colectomy or second biological line

Results

A total of 79 patients were included (Table 1). Median follow-up was 19 months (2-91); 78.5% were followed >6 months. At 6 months, 80.3% (61/76) and 37.3% (22/59) of the patients were in clinical and endoscopic remission, respectively. 54.3% received combination treatment with immunomodulators (50.6% thiopurines, 3.7% methotrexate). Dose intensification to weekly treatment occurred in 27.8% after median 9 months (4-48 months).

During follow-up 51% received corticosteroids at some point (26% topically-acting oral corticosteroids, 10% oral corticosteroids, 15% both). Of patients who received steroids, 55% (22/40) were able to continue adalimumab therapy. 2.5% of patients were hospitalised for a disease flare. 5.1% had an infection recorded during follow up, none discontinued the treatment. No other major adverse events were recorded.

In 22.8% (18/79) of patients, ADA was stopped due to treatment failure, mean 15 months after starting the drug (4-56 months), (Figure 1). None of these patients underwent colectomy at the time of stopping the drug; in 17/18 a second biological therapy was started (10 tofacitinib, 1 filgotinib, 1 upadacitinib, 2 ustekinumab, 2 vedolizumab, 1 golimumab). TDM was performed using a drug-sensitive ELISA, which is only able to detect antidrug antibodies when drug levels are low or absent. Drug levels at the time of stopping the drug were <5 µg/mL in 22% of patients (in 2 antibodies were detected), 5-8 µg/mL in 11% and >8 µg/mL in 67%.

Conclusion

In a real-world UC cohort, ADA appears to be an effective well tolerated first-line advanced therapy with the vast majority of patients reaching clinical remission and a significant proportion achieving mucosal healing.

Table 1. Cohort characteristics (N 79, frequency and %).

Figure 1: Kaplan-Meier survival analysis of time to ADA discontinuation.
P919 Crohn’s Disease Exclusion Diet as add-on therapy in refractory pediatric patients
Authors: Scarallo L , Pochesci S , Fioretti L , Paci M , Renzo S , Naldini S , Lacitignola L , Barp J , Banci E , De Blasi A , Lionetti P
Published: January 2024

Background

Despite the accumulating body of evidence of the efficacy and tolerability of Crohn’s disease exclusion diet (CDED) combined with partial enteral nutrition (PEN), there is still a paucity data regarding its use in combination with other medical treatments. We aimed at assessing its efficacy in re-inducing remission in pediatric CD patients experiencing disease relapse while on other maintenance therapies.

Methods

This was a single-center, retrospective, observational study conducted at an Italian national referral pediatric IBD center. Incident patients who received CDED coupled with PEN in the setting of the loss of response to other maintenance therapies from January 1st, 2020 to June 30th 2023 were included. Clinical remission at the end of each phase was defined by a weighted Pediatric Crohn’s Disease Activity Index (wPCDAI) below 12.5. Biochemical remission was defined by a c-reactive protein (CRP) lower than 0.5 mg/dL. A FC lower than 150 mg/kg was used as a surrogate of mucosal improvement (MI).

Results

25 patients (52% males) met inclusion criteria and were included in the analysis. Median disease duration at CDED+PEN initiation was 31 months (Q1-Q3: 8.4-13.8). The most frequent disease location was ileocolonic (64%), 3 (12%) patients had isolated colonic involvement. 9 (36%) patients had stricturing/penetrating phenotype. 16 patients (68%) were being treated with an anti-TNF-alpha agent, whereas 5 (20%) patients were receiving ustekinumab (Table 1). wPCDAI, CRP and FC significantly decreased after the firs 8 weeks of treatment (22.5 vs 2.5, 1 vs 0.2, 640 vs 360, p<0.001, p=0.019 and p=0.007, respectively). At the end of phase I, 19/25 (76%) of the patients achieved clinical remission, 15 (60%) patients had CRP levels within normal range and 7 (28%) of them had normalized FC. 18/25 patients (72%) had received Exclusive Enteral Nutrition (EEN) for the induction of remission at diagnosis. Patients who achieved clinical remission with the EEN course (i.e.: a wPCDAI of < 12.5 after a complete course of EEN) were more likely to achieve clinical remission when receiving CDED + PEN (11/13 vs 1/5, p=0.022).

Conclusion

CDED coupled with PEN is a valid treatment strategy in the setting of secondary loss of response to maintenance treatments in children with CD. A previous successful course of EEN was associated with higher rates of clinical remission at the end of phase I, thereby possibly identifying a subset of “nutritional responder” patients.
P939 Ozanimod-Exposed Patients with Ulcerative Colitis Undergoing Total Colectomy Exhibit Unique Histologic Changes in Lymph Nodes
Authors: Cohen N A , Weber C , Cheng J , Choi D , Garcia N , Choi N , Rubin D
Published: January 2024

Background

Ozanimod regulates lymphocyte egress from the spleen and lymph nodes into the systemic circulation. The histologic changes which occur in the lymph nodes of patients on these therapies is unknown. We describe histologic changes in lymph nodes from patients with UC who were treated with ozanimod and underwent subsequent colectomy due to treatment-refractory disease.

Methods

This retrospective study included patients with UC undergoing total colectomy for treatment-refractory disease who were treated with ozanimod within the 2 months prior to colectomy and a cohort of patients with UC undergoing colectomy who did not have ozanimod exposure. Histology of the lymph nodes from the mesentery of colectomy specimens were reviewed blindly by a hematophatologist (JXC) and an expert GI pathologist (CRW). Histopathological parameters were scored and demographic and clinical data were recorded.

Results

Of forty-five patients treated with ozanimod at our center, 6 (13%) required surgery for treatment-refractory disease. Colectomy specimen data were available for 5 patients (1 patient had surgery at an outside center). Lymph node specimens from 6 control patients with UC who had colectomy were also examined. Demographic and clinical data are summarized in Table 1. The duration of ozanimod therapy prior to surgery ranged from 6 to 24 weeks. Lymph nodes from patients treated with ozanimod had significantly greater extent of sinus dilatation than control patients (1.5 vs 0.67, p=0.022), they also had significantly more sinus histiocytosis (2.67 vs 1.67, p=0.03) (Figure 1). There was a tendency towards more Castleman-like angiotrophic hyperplasia (1.5 vs 1, p=0.34), plasma cell infiltration (1.5 vs 0.67, p=0.26) and subcortical interfollicular expansion (1.5 vs 0.83, p=0.1) in ozanimod treated patients. Patients treated with ozanimod and controls showed similar amounts of monomorphic lymphoid cells (1.3 vs 1.5, p=0.7), follicular hyperplasia (1 vs 1.1, p=0.8) and vascular proliferation (1.5 vs 1.5, p=1).

Conclusion

This study identifies unique histologic changes in the lymph nodes of patients with UC treated with ozanimod. These changes could be in keeping with the known mechanism of action of ozanimod and suggests that other inflammatory pathways were driving their disease activity in these patients. The significance of the changes, particularly the Castleman-like features, needs to be further investigated.

Table 1: Demographic and clinical data of patients treated with ozanimod and control patients

Figure 1: Representative images of lymph nodes from patients with UC treated with ozanimod and control patients showing significant sinus dilatation in patients receiving ozanimod
P952 Why do patients with Inflammatory Bowel Disease Take Part in Pharmaceutical Clinical Trials? A qualitative study of Clinical Trial Participants
Authors: Solitano V , Prins H , Archer M , Guizzetti L , Jairath V
Published: January 2024

Background

Recruitment rates to clinical trials in inflammatory bowel disease (IBD) continue to decline. A better understanding of motivations to participate as well as recommendations to reduce barriers to enrolment from a patient perspective may assist in design of future clinical trials.

Methods

We developed a 32-item electronic questionnaire to explore motivations, experiences and recommendations of patients with IBD, who have participated in pharmaceutical clinical trials in a tertiary centre in Canada.

Results

We distributed a total of 82 emails with surveys based on the patient details available to the study team. Using the DillMan Total Design Survey method, participants were followed up one week after the initial email with a reminder phone-call and we received 46 responses (56.1% response rate). Participants were mostly, male (58.7%), non-Hispanic white (93.5%), with a mean age of 45.5 years (SD 10.9). Most participants decided to participate in a clinical trial to benefit future patients with IBD (63.0%). Self-reported knowledge of the possibility of being assigned to placebo on a scale from 0 (no knowledge) to 100 (extremely knowledgeable) was a median of 100 (IQR 100-100) (Table 1). Half of participants (50.0%) reported they were worried about the possibility of receiving placebo, although the majority (63.0%) understood they could improve on placebo. The most challenging aspect reported was the number and length of questionnaires (32.6%), as well of the number of colonoscopies (30.4%). Strategies to increase enrolment recommended by participants were reduction in the chance of receiving placebo (43.5%), facilitating inclusion of patients who have failed multiple therapies (43.5%), allowing virtual visits (39.1%), including subtypes of disease that have traditionally been excluded in clinical trials (e.g., ostomies, fistula) (34.8%), and improving outreach to underrepresented populations (28.3%) (Figure 1). The vast majority (80.4%) reported their experience of participation to be better than expected and would recommend taking part in a clinical trial to other patients with IBD (97.8%).

Conclusion

Patients with IBD who took part in pharmaceutical trials reported a high level of satisfaction overall. The top three recommendations from patients to improve clinical trial design were reducing the chance of receiving placebo, allowing inclusion of patients who have failed multiple therapies and allowing for virtual visits to reduce travel burden to the clinical trial site. These results should help inform the design of patient centric clinical trials in IBD.
P955 The effect of appendicectomy on the clinical course of Ulcerative Colitis: Preliminary results
Authors: Visser E , Heuthorst L , Pathmakanthan S P , Wildenberg M E , D'Haens G R , Dijkgraaf M G W , Bemelman W A , Pinkney T D , Buskens C J
Published: January 2024

Background

Emerging evidence indicates an immunomodulatory role of the appendix in ulcerative colitis (UC). Previous studies have suggested a beneficial effect of appendicectomy in inducing and maintaining remission. Therefore, appendicectomy may be considered as an alternative or adjunctive treatment in UC.

Aim

To evaluate the efficacy of appendicectomy in maintaining remission in UC patients.

Methods

Adult patients with established UC in complete clinical and endoscopic remission (defined as Mayo score <3 with endoscopic subscore of 0 or 1) following medical induction treatment for disease relapse within 12 months prior to randomisation, were enrolled in the Netherlands and United Kingdom. Patients were randomised (1:1) to undergo appendicectomy (intervention group) or continue maintenance medical therapy (control group). The primary outcome was the one-year UC relapse rate (defined as a total Mayo-score score ≥5 with endoscopic subscore of ≥2). To detect a clinically relevant decrease in relapse rate from 40% to 20%, 82 patients per study arm were needed to achieve 80% power. The last patient was included in September 2022, so analysis of the primary outcome parameter is expected to start soon. Trial progress, including the accumulated number of (serious) adverse events (SAE) in both groups, were presented annually to the Data Safety Monitoring Board. Therefore safety data is available.

Results

In total, 99 patients were included in the intervention group and 99 patients in the control group. There were 86 males and 112 females, with a median age of 41 years (IQR 33-52). Baseline characteristics were comparable in both groups, with the majority of patients having proctitis (38.9%) or left sided colitis (35.9%). Three SAEs were reported in the appendicectomy group, 2 of which were related to the surgical procedure (reintervention for obstructive ileus and postoperative hematoma) and one hospitalisation for clostridium infection. One SAE was reported within the first year in the control group (appendicitis). The one-year reported colitis-associated adverse event rate was significantly lower in the appendicectomy group when compared to the control group (46.4% vs. 63.9%, P=0.02). During follow up there were no colectomies in the appendicectomy group, whereas three patients underwent colectomy for therapy-refractory disease in the control group.

Conclusion

Appendicectomy in patients with UC has the possibility to decrease the rate of colitis-associated (serious) adverse events. These results suggest that the final analysis of the primary outcome parameter (relapse rate) could demonstrate that appendicectomy is superior to standard medical therapy alone in maintaining remission in these patients.
P978 Changing therapy to achieve endoscopic healing in asymptomatic patients with IBD: When is perfect the enemy of good?
Authors: Systrom H , Rai V , Singh S , Baidoo L , Cheifetz A , Devlin S , Gecse K , Irving P , Kaplan G , Kozuch P , Ullman T , Sparrow M , Melmed G , Siegel C
Published: January 2024

Background

The treat-to-target strategy for inflammatory bowel disease (IBD) recommends optimising or changing therapy in patients who have not achieved clinical remission and endoscopic healing. In asymptomatic patients, the potential benefit of changing therapy to achieve endoscopic healing is less clear, particularly since <40% typically achieve endoscopic healing with current therapy. We sought to define appropriateness of changing therapy in asymptomatic IBD patients with active endoscopic inflammation.

Methods

Using the RAND/UCLA Appropriateness Method, a panel of 9 IBD specialists considered appropriateness of changing therapy in 16 scenarios of patients with ulcerative colitis (UC) and 96 scenarios of Crohn’s disease (CD), rated on a 9-point Likert scale as inappropriate (1-3), uncertain (4-6), or appropriate (7-9). Patients in all scenarios were asymptomatic with active endoscopic disease; variables included disease extent, behaviour, prior treatment, recent disease progression, and prior disease complications. Current therapy was assumed to be optimised, so the only options were changing therapy or continuing current therapy. An additional 14 scenarios explored patient factors that might influence treatment decision-making. Ratings were collected via online anonymous survey, discussed at an in-person meeting, then finalised in a second anonymous survey using a modified Delphi approach. Disagreement was assessed using a validated index.

Results

Panelists rated it appropriate to change therapy (i.e., expected benefit sufficiently exceeds expected negative consequences) in 96/126 scenarios, generally those with progressive, complicated, and/or extensive disease; 27 scenarios of mild and/or stable disease were rated uncertain, particularly with prior exposure to ≥3 drug classes. Changing therapy in asymptomatic patients was rated inappropriate in 3 scenarios: in Mayo 1 UC previously treated with ≥3 therapy classes with no endoscopic progression in the last year; in any patient who showed endoscopic improvement over the last year; and in any patient with CD who had only scattered aphthous ulcers. Patient age >65 years influenced a decision to change therapy specifically for anti-TNFs and JAK inhibitors; the possibility of pregnancy also influenced decision-making. Despite variability in ratings, the threshold for disagreement was not crossed for any scenario.

Conclusion

Our panel of IBD specialists rated appropriateness of changing therapy to achieve endoscopic healing in asymptomatic patients with UC and CD in a variety of scenarios. Our findings can be used to help guide clinical decision-making in this population until data from ongoing randomised studies are available (NCT05230173).
P979 Diet, disease activity and extraintestinal symptoms in IBD outpatients
Authors: Wilke E L , Knoedler L L , Atanasova K , Ebert M P , Reindl W , Thomann A K
Published: January 2024

Background

Patients with inflammatory bowel disease (IBD) show higher rates of fatigue and symptoms of depression and anxiety. Growing evidence reports a beneficial influence of plant- based diets on IBD as well as psychological disorders. The Mediterranean diet shows favorable characteristics in this regard and is simple to implement. We aimed to examine adherence to a Mediterranean diet as well as its associations with disease activity, quality of life and fatigue or affective symptoms in outpatients with IBD.

Methods

We delivered questionnaires to IBD outpatients, assessing adherence to the Mediterranean diet (MEDAS), symptoms of depression and anxiety (HADS), as well as fatigue (FACIT-F) and quality of life (SHS). Disease activity was measured with HBI or pMS, respectively. Associations between the parameters were determined using spearman correlation.

Results

We collected data of n=281 patients. Adherence to the Mediterranean diet was generally low in our sample with a median MEDAS score of 6 (0-13). The greatest deficit was observed in the regular consumption of fish (10 %) and fruit (16.6 %). However, we found a very high adherence for olive oil as the main source of fat (81.9 %), as well as a preference for white meat over red meat and processed meats (63.7 %). The prevalence of depressive symptoms (HADS-D ≥ 8) was 22.4 %, while symptoms of anxiety (HADS-A ≥ 8) were found in 35.9 % of the participants. Severe fatigue (FACIT < 30) was present in 33.8 % of the patients. Patients with clinically active disease were more likely to experience fatigue (ρ=-.231, p=<.001), symptoms of anxiety (ρ=.132, p=.010), depressive symptoms (ρ=.216 p=<.001), and reduced quality of life (ρ=.359, p<.001), all Figure 1a. There were no significant associations between the MEDAS score and disease activity (ρ=.033, p=.522), fatigue (ρ=-.009, p=.831), anxiety symptoms (ρ=.049, p=.294), or depressive symptoms (ρ=-.035, p=.461). Women showed significantly higher adherence to Mediterranean diet (mean MEDAS score 5.2 vs. 6, p=.003). We found a negative correlation between adherence to Mediterranean diet and level of calprotectin (ρ=-.146, p=.023, Figure 1b).

Conclusion

The preliminary analysis of our sample suggests low levels of adherence to the Mediterranean diet in our patient population. Contrary to our expectation, there were no statistically significant associations between diet and disease activity, quality of life, or psychological complaints. However, the inverse correlation between adherence to Mediterranean diet and level of calprotectin can support the anti-inflammatory characteristics this diet. It remains unclear, to which intent an anti-inflammatory diet can impact the course of disease and clinical symptoms in patients with IBD.