bluuebunny/crossref_metadata_2025 huggingface dataset:
P704 Safety of Immunosuppression in A Prospective Cohort of Inflammatory Bowel Disease Patients with a HIstoRy of CancEr: The SAPPHIRE Registry
Authors: Axelrad J , Jiang Y , Colombel J F , Scherl E , Lukin D , Chang S , Chen L , Katz S , Kwah J , Swaminath A , Sultan K , Villagra C , Jandorf L , Itzkowitz S
Published: January 2024

Background

For patients with inflammatory bowel disease (IBD) and a history of cancer, retrospective studies have failed to find evidence suggesting that exposure to biologic and/or immunomodulator (IMM) agents was associated with new or recurrent cancer. The SAPPHIRE Registry was developed to prospectively examine this issue.

Methods

Patients with IBD who had a confirmed first (index) cancer 5 years prior to enrollment were recruited from centers affiliated with the New York Crohn’s and Colitis Organization (NYCCO) since 2016. Patients receiving chemotherapy or radiation therapy at enrollment or recurrent cancer within the last five years were excluded. The primary outcome was the development of an incident cancer stratified by IBD therapy exposure and adjusted for index cancer stage, index cancer type, sex, smoking history, and age at index cancer in a Cox proportional hazards model.

Results

302 patients were analyzed. Median age at IBD diagnosis was 31.5. Patients were 47% male, 88% white, and 61% never smokers. Index cancers were solid organ (138; 46%), dermatologic (100; 33%) GI (34; 11%), hematologic (27; 9%), or of other types (3; 1%); most index cancers (excluding non-melanoma skin cancer) were diagnosed as Stage 1. Following the index cancer, 90 (30%) patients were not exposed to any immunosuppression, and the other 212 were exposed to immunosuppressive therapy: 142 biologic monotherapy (anti-TNF, anti-integrin, anti-IL12/23, anti-IL23; 47%), 13 anti-metabolite monotherapy (mercaptopurine, azathioprine, methotrexate; 4%), 41 biologic + anti-metabolite combination therapy (14%), and 16 exposed to small molecules (JAK inhibitors, ozanimod; 5%). During follow-up, 46 (15%) patients developed subsequent cancers (25 new, 21 recurrent): 22 (48%) dermatologic, 15 (33%) solid, 7 (15%) GI, and 2 (4%) hematologic malignancies at a median age of 63.5. Patients not exposed to immunosuppression experienced incident cancer at a rate of 2.58/100 person-years (PY, Table). Those exposed to immunosuppression had a rate of 5.12/100 PY, representing an additional 2.54 cancers/100 PY (95% CI: 0.22, 4.85). In a time-varying Cox proportional hazards model adjusting for clinical and demographic characteristics, the adjusted hazard ratio for incident cancer for patients exposed to immunosuppressive therapy compared to unexposed patients was 1.36 (95% CI: 0.73, 2.52). Excluding non-melanoma skin cancer, the adjusted hazard ratio was 1.38 (95% CI: 0.66, 2.91).

Conclusion

In this ongoing prospective study, we have thus far found no association between immunosuppressive IBD therapy and risk of developing new or recurrent cancer. Ongoing enrollment and follow-up, specifically for individual drug classes and cancer types, are required to confirm these findings.
P709 Role of NOD2 single nucleotide polymorphisms on ustekinumab drug durability in adult patients with Crohn’s disease
Authors: Elleisy N , Behnisch S , Huth A , Schäffler H , Jaster R , Lamprecht G , Reiner J
Published: January 2024

Background

Ustekinumab (UST), a monoclonal antibody targeting the p19 subunit of the pro-inflammatory Interleukins 12 and 23, is a therapeutic option in patients with Crohn’s disease (CD) with high efficacy, although some patients will have to cease therapy with UST due to primary non-response, secondary loss of response, or adverse events. Single nucleotide polymorphisms (SNPs) in the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene have been proposed as a prognostic factor in CD. Whether these NOD2 SNPs have an impact on UST drug durability among adult CD patients remains unclear.

Methods

CD patients were genotyped for the three most common NOD2 SNPs (rs2066844, rs2066845, and rs2066847). Hazard ratios (HR) for risk of NOD2 SNPs on UST durability were calculated using univariable and multivariable cox proportional hazard regression adjusting for age at first UST prescription, previous surgery, Montreal A, L, and B classification, present perianal disease, and previous anti-TNF exposure. Statistical analysis was conducted using SPSS. A two-tailed P value < 0.05 was considered statistically significant. All patients provided written informed consent.

Results

92 CD patients were included in the analysis. Of those, 72 continued receiving UST until the end of the study. In univariable and multivariable analyses, NOD2 SNPs were not independent prognostic factors for UST drug durability (P>0.05 for all three NOD2 SNPs). However, age at first UST prescription (adjusted HR [aHR] 0.96, 95% confidence interval [CI] 0.93-1.00, P=0.028 for all tested NOD2 SNPs) and present perianal disease (aHR 2.65, 95% CI 1.11-6.31, P=0.028 for all tested NOD2 SNPs) were independent predictors of ustekinumab drug durability.

Conclusion

Among adult Crohn’s disease patients being treated with ustekinumab, the presence of NOD2 SNPs did not have a significant impact on ustekinumab drug durability.
P717 Evaluating the performance of Large Language Models in responding to patients' health queries: A comparative analysis with medical experts
Authors: Yan Z , Lu S , Xu D , Yang Y , Wang H , Mao J , Fan Y , Chen Y , Tseng H C
Published: January 2024

Background

Patients with chronic diseases exhibit a heightened interest in seeking health information, and access to high-quality information can positively impact clinical outcomes. While previous research on static internet text/video information has highlighted concerns about low-barrier creation leading to low-quality content, it remains uncertain whether similar issues persist in responses generated by Large Language Models (LLMs). Assessing the ability of LLMs in responding to medical queries provides valuable insights for their application in healthcare settings.

Methods

In alignment with open science principles, we utilized real patient queries from the China Crohn's and Colitis Foundation (CCCF) series "Questions and Answers on Ulcerative Colitis and Crohn's Disease." The dataset comprised questions posed by patients and corresponding answers from medical professionals, collected from outpatient visits and online social media. In September 2023, 263 patient questions were sequentially input into ChatGPT-3.5 (August 3, 2023 version), and the resulting responses were compiled alongside the original medical professional responses, forming 263 modules. Three Inflammatory Bowel Disease (IBD) specialist physicians and three IBD patients were invited to assess each module. Evaluators were instructed to: 1) choose their preferred response version, and 2) provide a multidimensional Likert 5-point subjective assessment using a crowdsourcing strategy. Additionally, the CRIE 3.0 team conducted an automated objective analysis of Simplified Chinese readability.

Results

Mann-Whitney U tests on text readability levels (median: 7th grade for both medical professionals and ChatGPT responses; Q1: 6th grade; Q3: 8th grade) revealed no significant difference (p=0.87), suggesting ChatGPT's performance align well with recommended literacy levels for popular science publications and is comparable to the average education level in China.

Conclusion

Cautiously interpreting our findings, ChatGPT's preliminary performance appears comparable to specialized IBD physicians, indicating its potential utility in patient community Q&A. Integrating ChatGPT or similar LLMs into the drafting or refinement stages of health texts is feasible. However, due to the presence of AI hallucinations and the consensus in most experimental conclusions, direct use of large language models for patient Q&A services is not recommended. Recognizing the variability in health information understanding between medical professionals and patients can enhance patient education efforts.
P718 Observational real-world evidence on the efficacy and safety of Janus Kinase inhibitors (JAKi) in the treatment of moderate to severe Active Ulcerative Colitis (UC)
Authors: Al-Zarrad D , Yeung K , Arebi N , Dyall L , Kamperidis N
Published: January 2024

Background

Janus kinase inhibitors (JAKi) are the first orally administered treatment for Ulcerative Colitis (UC). The JAK family comprises of four intracellular tyrosine kinases inhibitors (JAK1, JAK2, JAK3 and Tyrosine Kinase 2). Inhibition of the JAK kinases lead to dampening of the inflammatory cytokines which drive Inflammatory Bowel Disease (IBD).

Tofacitinib was the first generation pan-JAKi. This was followed by second generation JAKi: Filgotinib and Upadacinib which preferentially inhibit JAK1.

We report on the real-world evidence on the efficacy and safety of JAKi in the treatment of UC in a tertiary IBD treatment centre.

Methods

Patients attending the IBD clinic at weeks 8-12 of initiation of therapy were included. Baseline demographics, disease activity and previous therapies were recorded. Clinical response was measured using the SCCAI and biochemical response was measured using calprotectin and CRP.

We defined clinical response as ≥3 points reduction from baseline SCCAI, and clinical remission as SCCAI Score of <2.5, and / or biochemical remission as a CRP of less than 5 mg/L and a calprotectin level of < 250 mg/g. We also assessed treatment persistence, and the reasons for treatment cessation.

Results

The UC populations are shown in Table 1. 52 patients were included and an additional 24 patients who discontinued therapy early on were assessed to review secondary outcomes. Table 1 summarises the comparative outcomes of the JAKi. 81% and 63% of patients achieved clinical and biochemical remission respectively. Overall, 31% discontinued treatment due to lack of efficacy or adverse events. 60% of patients reported adverse events (AEs), 25 % of patients discontinued treatment due to AEs and 84% of patients continued treatment despite reporting AEs. The most common AEs were hypercholesteremia and cold and flu like symptoms and the most common AEs related with treatment discontinuation were recurrent infection or persistent deranged liver functions contributed to patients’ history of primary sclerosing cholangitis. No Serious Adverse Events were reported. 60% of patients on tofacitinib developed side effects and persisted with therapy, which included hypercholesteremia (67%), shingles (11%), flu like symptom (11%) and hair loss (11%). 53% had side effects with Filgotinib; hypercholesteremia (25%), cold like symptoms (25%), chest infection (13%), shingles (13%), acne (13%). 68% developed side effects with Upadacitinib; reports of acne (20%), cold and flu (33%), shingles and mood swings (7%) and high cholesterol (67%).

Conclusion

In this real-world cohort of UC patients, JAKi was effective in inducing remission and had an acceptable safety profile. The observed safety profile was as expected compared to clinical data results.
P719 Vitamin and micronutrient excess in patients with Crohn’s disease under oral ambulatory exclusive enteral nutrition
Authors: Oliveira R , Mendes B , Cunha Neves J , Amorim E , Roseira J , Tavares de Sousa H
Published: January 2024

Background

Exclusive enteral nutrition (EEN) is recommended for preoperative nutritional optimization (PNO) in adult Crohn's disease (CD) patients. However, during ambulatory oral EEN, a lack of routine monitoring for vitamins may occur, with a potential risk of hypervitaminosis-related toxicity, which remains unexplored. This study aims to assess the serum levels of vitamins and micronutrients in CD patients undergoing EEN and to examine its potential impact.

Methods

Complicated phenotype CD patients followed at a University Tertiary Hospital who were started on oral EEN June 2021 - June 2023 were prospectively included. EEN composition was determined and modified by an IBD nutritionist according to patients’ nutritional status and needs and laboratory values. Compliance was monitored daily, both for in- and outpatients. Patients’ weight and serum values (albumin, C-reactive protein [CRP], iron, folic acid, and vitamins B1, B6, B12, A, D, E and K) were monitored weekly.

Results

Nine patients (median age 29 years, 55.6% female) received a median of 24 (IQR 14.5-25.0) days of EEN, for PNO of symptomatic stricturing (7, 77.8%) or abdominal penetrating disease (2, 22.2%). All patients were discharged while on EEN, which was maintained until elective surgery (4, 44.4%) or the planned start of advanced medical therapy (5, 55.6%), with EEN successfully avoiding emergent surgeries. Patients were started on a combination of hypercaloric-hyperproteic and hypercaloric-normoproteic ready-to-drink concentrated polymeric formulas, providing 30 kcal/kg/d and 1.2-1.5g/kg/d of protein. EEN daily volume ranged from 1000 to 1400mL. Compliance was 100%, requiring flavour adjustments for tolerance. Table 1 illustrates changes over time in patients' weight and serum levels of interest. Resolution of anaemia and hypoalbuminemia was achieved, while weight was maintained . Hypervitaminosis cases were remarkably detected: 5 (55.6%) for vitamin B1, 4 (44.4%) for A, 2 (22.2%) for E, and 3 (33.3%) for K, with increasing trends over time. However, no symptoms related to hypervitaminosis were reported.

Conclusion

Our study on PNO EEN in CD uncovered a gap in routine monitoring for essential vitamins during EEN. While achieving significant clinical improvement, our findings revealed subtle and asymptomatic cases of hypervitaminosis in short-term EEN courses. These results underscore that vitamin monitoring is advisable during EEN, especially in prolonged EEN protocols due to possible hypervitaminosis-related toxicity.
P724 Long-term outcomes of exclusive enteral nutrition in the peri-operative period for Crohn’s disease: A seven year follow-up study
Authors: Ragatha R , Estridge P , Shams O , Bethune R
Published: January 2024

Background

Exclusive enteral nutrition (EEN) is a recommended first-line treatment for Crohn’s disease flares in the paediatric population. Its use has yet to translate widely to the adult population. There is growing evidence for the use of EEN in the pre-operative setting to downstage the disease process and improve short term surgical outcomes. Little is known in this context regarding the long term effects of pre-operative EEN. Our study reports on follow up data for a cohort of patients who underwent surgery following pre-optimisation with EEN compared to those who did not. We assessed long term complications, disease recurrence and disease control as our key outcomes.

Methods

We carried out a seven year follow up study of the patients included in a retrospective, matched cohort trial conducted in a single, tertiary care, inflammatory bowel disease centre, in the UK. Patients pre- optimised with EEN prior to surgery were compared to a matched control cohort.

Results

Median follow up period was seven and six years for EEN and control groups respectively. Patients in the EEN group were more likely to be on maintenance medical therapy compared to control (73.47% vs 46.67%, p=0.005), however, admission rates and clinical recurrence rates were similar between groups (32.65% vs 24.66%, p=0.33 and 71.43% vs 65.58%, p=0.42). There was a moderate difference in complication rates beyond six months in favour of the EEN group (5.55% vs 17.80%, p=0.08). EEN patients were more likely to need further surgery however, this observation was not sustained when surgery for peri-anal disease was excluded (22.45% vs 13.69%, p=0.21)

Conclusion

Pre-optimising patients with EEN prior to Crohn’s disease surgery may improve short term surgical outcomes, it is unlikely to improve long term disease outcomes, based on results from this study.
P726 A phase 2 study investigating the efficacy and safety of dupilumab versus placebo in adults with moderately to severely active ulcerative colitis with an eosinophilic phenotype
Authors: Gottlieb E , Binion D , Feagan B , Laws E , Nivens C , Maloney J , Abdulai R , Radin A , Glotfelty L
Published: January 2024

Background

Ulcerative colitis (UC) is a heterogeneous, chronic inflammatory disease, with many different drivers of pathogenesis, characterised by inflammation of the colon mucosa, relapsing–remitting disease course and variable response to therapy. Around 30–55% of patients with UC are refractory to treatment during the induction phase, despite the availability of molecular targeted agents. Recent studies have investigated a potential link between eosinophilia and increased disease activity, poorer clinical outcomes and response to therapy.

Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation in multiple diseases. It is approved for treatment of atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic oesophagitis and prurigo nodularis. The phase 2 LIBERTY-UC SUCCEED (NCT05731128) study is designed to investigate the efficacy and safety of dupilumab versus placebo in adults with moderately to severely active UC with an eosinophilic phenotype.

Methods

Approximately 100 patients will be randomised 1:1 to receive dupilumab or placebo treatment for 52 weeks. Key inclusion criteria include age ≥18 years, moderately to severely active UC (modified Mayo score 5–9), biomarker enrichment, and inadequate/non-response, loss of response, or intolerance to standard biologic therapy and/or oral corticosteroids, ASA compounds, immunomodulators or small molecules. Key exclusion criteria include severe extensive colitis (defined by current hospitalisation, requirement for surgery for UC within 12 weeks of screening), prior medical history of eosinophilic colitis, or presence of intestinal failure. Participants who qualify will have the opportunity to receive open-label dupilumab.

Results

The primary endpoint is proportion of patients in clinical remission at Week 24, defined as a modified Mayo score of ≤2 with a stool frequency score ≤1, a rectal bleeding score = 0 and a Mayo endoscopic subscore ≤1 with absence of friability. Higher scores indicate greater disease severity. Secondary endpoints include the proportion of patients achieving clinical response by modified Mayo score at Week 8, 24 and 52, and incidence of treatment-emergent or serious adverse events.

Conclusion

The phase 2 LIBERTY-UC SUCCEED study will evaluate the efficacy and safety of dupilumab therapy in adults with moderately to severely active UC with an eosinophilic phenotype. This will aid in addressing the need for precision medicine approaches to treat UC.
P730 Edema index as a more sensitive indicator of nutritional status with Crohn’s disease
Authors: Peng Y , Liu X
Published: January 2024

Background

Crohn's disease (CD) often presents with malnutrition due to the impaired mucosal barrier accelerating the loss of protein. The edema index can indicate protein consumption. This study aims to confirm whether the edema index could be a nutritional assessment for CD patients.

Methods

The study was conducted at Xiangya Hospital Central South University between May 2023 and July 2023, including CD patients and the control group. In both groups, bioelectrical impedance analysis was performed, and the edema index defined as extracelluar water/total body water (ECW/TBW) was calculated. The demographic data and body composition parameters were collected through the medical system. The control group consisted of healthy adults, strictly matched for gender, age, and BMI in a 1:1 case-control manner. Univariate analysis and multivariate analysis were used to compare the differences in nutrition-related indicators between both groups.

Results

A total of 128 subjects were included in the final cohort with 50% each of CD patients and healthy individuals. There were no significant differences in gender, age, BMI. Fat free mass, muscle mass, basal metabolic rate (BMR), and visceral fat rating were similar in both groups (P > 0.05). Compared to the control group, CD patients had significantly lower fat mass (9.26 ± 5.38 vs.16.63 ± 10.67, P = 0.006), bone mass (2.16 ± 0.41 vs. 2.52 ± 0.57, P = 0.019), but a higher level of edema index (41.07 ± 2.38 vs. 38.53 ± 5.62, P = 0.015). Multivariate logistic regression analysis revealed that edema index was an independent factor to malnutrition in CD patients (OR: 1.665, 95% CI: 1.158-2.395, P = 0.006).

Conclusion

A higher edema index in CD patients demonstrates their worse nutritional status compared to healthy subjects. The edema index may serve as a more sensitive and noninvasive indicator to assess nutritional status in CD patients.
P733 Long-term effectiveness and acceptability of switching from intravenous to subcutaneous infliximab in patients with inflammatory bowel diseases treated with intensified doses: the REMSWITCH-LT study
Authors: Buisson A , Nachury M , Bazoge M , Yzet C , Wils P , Dodel M , Coban D , Pereira B , Fumery M
Published: January 2024

Background

We recently demonstrated that switching from intravenous to subcutaneous infliximab is safe and well-accepted at short-term in IBD patients including those with intensified IV regimen. However, the long-term risk of relapse in these patients remains unknown.

We assessed the long-term effectiveness and acceptability of switching from intravenous to subcutaneous infliximab in patients with inflammatory bowel diseases (IBDs) treated with or without intensified intravenous regimen.

Methods

In this prospective multicenter observational study, IBD patients in clinical remission (partial Mayo score ≤ 2 or Harvey-Bradshaw index ≤ 4) were switched to a unique dose of subcutaneous infliximab (120 mg every other week). Pharmacological and biological data were collected at baseline, 6 months and at last follow-up (median follow-up : 18 [15-20] months). Relapse was defined as clinical relapse or fecal calprotectin increase ≥ 150 mg/g compared with baseline.

Results

Among 184 eligible patients, 72.3% (n = 133/184) agreed to switch. At M6, a relapse occurred in 10.2% (n = 6/59), 7.3% (n = 3/41), 16.7% (n=3/18), and 66.7% (n=10/15) (P < .001) of patients receiving 5 mg/kg every 8 wks, 10 mg/kg every 8 wks, 10 mg/kg every 6 wks, and 10 mg/kg every 4 wks, respectively. At 18 months, the rate of relapse was 13.6% (n=8/59), 17.7% (n=7/41), 33.3% (n=6/18), and 86.7% (n=13/15) (P < .001) of patients receiving 5 mg/kg every 8 wks, 10 mg/kg every 8 wks, 10 mg/kg every 6 wks, and 10 mg/kg every 4 wks, respectively.

Dose escalation led to recapture clinical remission in 82.1% (23/28) of the patients, including 83.3% (15/18) and 80.0% (8/10) in those receiving 240 mg every other week or 120 mg every week, respectively.

Infliximab serum levels increased after the switch (P < .0001) except for patients receiving 10 mg/kg every 4 wks. In multivariable analysis, 10 mg/kg every 4 wks regimen (OR= 61.0; [6.0-600.1], p <0.001) and 10 mg/kg every 6 wks regimen (OR=4.7; [1.1-20.2], p = 0.039) had a higher risk of relapse at 18 months as well as reduced (58.3%) or stable (52.6%) infliximab serum levels between baseline and visit 1 compared with increased serum levels (19.7%) (P = 0.006 and P = 0.008, respectively).

Patients’ acceptability (10-point scale) was improved by the switch (6.9 ± 1.6 for IV vs 8.6 ± 1.4 at V1 after the switch; P < .0001) and did not decrease over time during SC maintenance regimen 8.8 ± 1.3 at 6 months and 8.8 ± 1.3 at 18 months. No severe adverse event was reported.

Conclusion

Switching from IV to SC infliximab 120mg eow is safe and well-accepted leading to a low long-term risk of relapse in IBD patients. Tight monitoring and escalated dose should be recommended for patients receiving 10mg/kg/6 weeks and 4 weeks, respectively.
P736 Class 4 Fistulizing Perineal Disease after Proctectomy for Crohn’s Disease: A Multicentre Study
Authors: Khan A , Khan I , Ward T , Cohen B , Valente M , Holubar S
Published: January 2024

Background

The TOpCLASS International Consortium recently described a paradigm shifting classification scheme for perianal Crohn’s disease, based on the desired patient goals of care. Class 4 perineal fistulizing disease is a CD that persists after proctectomy, and there are limited data defining this entity. We sought to determine the rates of clinical perineal fistulizing disease after proctectomy and to secondarily define the risk factors for recurrence.

Methods

Adult patients with CD who underwent perineal resection with proctectomy or proctocolectomy at three hospitals within our institution’s health network between 2009 and 2021 were retrospectively reviewed. The exclusion criteria included a preoperative diagnosis of ulcerative colitis or indeterminate colitis, and patients who underwent restorative proctectomy. Extracted data included baseline demographic data, preoperative medical treatment for CD, proctectomy indication, clinical recurrence of perineal disease, and resolution of perineal disease.

Results

A total of 405 patients with Crohn’s disease were included, including 190 (46.9%) who underwent proctectomy and 215 (53.1%) who underwent proctocolectomy. The median age was 44 years (IQR 33-58) and 58.8% of the patients were female. Within three months prior to surgery, 36% were exposed to biologic therapy, 29.1% to immunomodulators, and 11.4% to corticosteroids. During a median follow-up of 4 years, clinical recurrence of fistulizing perineal CD occurred in 62 (15.3%) patients, including five patients with perineal-vaginal fistulas and one with adenocarcinoma in the fistula tract. The median time to the development of perineal disease was 6.5 months (IQR 3-23 months). Factors associated with perineal disease included younger age (38 vs. 46 years; p <0.01), female sex (71% female vs. 56.6% female; p=0.03), preoperative corticosteroid use (19.4% vs. 9.9%; p=0.031), and the presence of perianal CD, regardless of the indication for proctectomy (85.4% vs 60.1%; p<0.01). After treatment for class 4 disease, perineal symptom resolution was observed in 40 (62.9%) patients. There were 79 (19.5%) patients underwent examination under anesthesia (EUA) for perineal disease, with a median of 2 EUA’s (range 1-21). Preoperative biological therapy was not associated with recurrent perineal disease (p= 0.29).

Conclusion

Perineal CD after proctectomy is common and frequently requires multiple surgical interventions. Younger age, female sex, preoperative corticosteroid use, and the presence of perianal disease may benefit from a more intensive postoperative review and consideration of the continuation or early initiation of prophylactic post-proctectomy CD medical management with biologics.
P737 Poor body image is associated with significant depression, anxiety and self-harm in people with inflammatory bowel disease
Authors: Barnes A , Prosser R , Mountifield R
Published: January 2024

Background

Body image dissatisfaction is common in inflammatory bowel disease (IBD) and is associated with worse quality of life in this population. In other populations body image dissatisfaction has been associated with psychological distress. We aimed to investigate the relationship between body image and depression, anxiety, and self-harm in an IBD population.

Methods

IBD patients at a tertiary IBD referral centre were sent a pre-clinic survey to be undertaken once a year. This survey included a validated measure of body image dissatisfaction – the body image scale (BIS) – with a BIS >= 10 indicating Body Image Dissatisfaction. Demographic data and measures of depression (Patient health questionnaire 9 (PHQ9), and anxiety (Generalised anxiety disorder-7 (GAD7)) were also obtained.

Results

There was 146 responses to the questionnaire, majority female (64%), median age 42 years interquartile range (29-58), 57% Crohn’s disease. A BIS over >= 10 was seen in 35.3%, with mean (SD) BIS score 8.5 (7.5). Consistent with previous literature BIS score was higher in females (11.3 (1.2) v 3.4 (3.5), p<0.001). BIS score was higher in obesity (11.0 v 7.2, p=0.049), however correlation with weight was poor (-0.044), and overall body weight was not higher in BIS>=10 (77.5 (2.8) v 82.1 (4.8) p=0.37), and similarly no difference seen in BMI (30.0 (1.5) v 28.3 (1.2) p=0.41).

BIS score and depression score (PHQ9) correlation was strong (ro=0.56), and similarly for anxiety severity score (ro=0.57). More frequent self-harm was associated with worse body image dissatisfaction (Figure 1 oneway ANOVA). Self-harm or suicidal ideation more than half the days was associated with a BIS score over 10 (p=0.012 Chi2, Odds ratio 4.16 for self-harm given BIS over 10).

Conclusion

Body image dissatisfaction is associated with self-harm, depression and anxiety, In addition to its known relationship with lower quality of life. Consideration should be given to developing body image targeting interventions in IBD populations and future research should consider interventional trials in this area.
P738 Response to etrasimod treatment in ulcerative colitis is associated with a reduction of circulating B and pro-inflammatory T cells: a single-cell-based post-hoc sub-analysis of the ELEVATE UC 52 trial
Authors: Weidinger C , Milek M , Hecker J , Haag L M , Freise I , Obermayer B , Beule D , Ryan R D , Crosby C , Siegmund B
Published: January 2024

Background

Etrasimod (ETR) is an oral, once-daily, selective sphingosine 1-phosphate receptor 1,4,5 (S1PR) modulator for the treatment of moderately to severely active ulcerative colitis (UC). The mechanism of action is based on a retention of lymphocytes in lymphatic tissue hindering circulating lymphocytes from entering the gut and causing inflammation. However, the effect of ETR on immune cell function and composition is not well characterized. In addition, it is unknown whether the response of UC patients to ETR treatment is associated with specific immune cell signatures.

Methods

Single-cell RNA sequencing (scRNAseq), mass cytometry (CyTOF) and clinical data integration were used to characterize the effects of 12 weeks of treatment with ETR on the immune composition and function of peripheral blood mononuclear cells (PBMCs) collected from 15 UC patients at weeks 0 and 12 during the ELEVATE UC Phase 3 clinical trial. As an exploratory cohort, PBMCs from 5 UC patients reaching the primary endpoint of clinical remission at week 12 (modified Mayo score <2), 5 UC patients not responding to ETR treatment (modified Mayo score >2) and 5 placebo-treated UC patients were included. 30 samples were processed for scRNAseq; additionally, 28 blood samples were ex-vivo stimulated with ionomycin/PMA for 4 h and cytokine production was assessed by CyTOF. To determine the effects of ETR in UC patients, immune cell function and composition were compared intra-individually between weeks 0 and 12. Subsequent comparisons between ETR responders, non-responders and placebo-treated UC patients were performed to discriminate responders from non-responders.

Results

Significant reductions in T and B cell subsets, along with increases in the abundance of dendritic and monocytic cells, were observed in responders by week 12 of -treatment. Importantly, ETR treatment significantly reduced circulating T cells producing pro-inflammatory cytokines, including TNFα and IFNγ, and S1PR modulation led to a mitigation of naïve and effector memory CD4 and CD8 T cells in ETR-treated UC patients achieving clinical remission. In contrast, patients not responding to ETR treatment had significantly higher frequencies of both naïve and TNFα-producing CD4 T cells by week 12.

Conclusion

In line with the described role of S1PR in lymphocyte trafficking, single-cell analyses of circulating immune cells from ETR-treated UC patients confirmed a significant reduction in B cells and pathogenic T cell subsets after ETR treatment providing an in-depth cellular characterization of S1PR modulation in UC patients thereby contributing to a better understanding of the key mechanism of action of ETR. However, these findings require validation in larger cohorts.
P758 Effectiveness and tolerability of methotrexate monotherapy in Crohn’s disease patients: A multicenter observational study
Authors: Park J , Jaeyoung C , Soo Jung P , Jae Jun P , Tae Il K , Won Ho K , Hyuk Y , Jae Hee C
Published: January 2024

Background

Methotrexate monotherapy is recommended as a maintenance therapy for Crohn’s disease (CD). However, long-term follow-up data are scarce. We aimed to examine the effectiveness and tolerability of methotrexate monotherapy in 94 CD patients from three IBD Clinics in Korea.

Methods

Patients with active CD treated with methotrexate monotherapy were included. Clinical characteristics, laboratory indicators, endoscopy indices were evaluated at baseline, 6, 12, and 24 months. Independent factors associated with long-term clinical and endoscopic outcomes were determined.

Results

Methotrexate was administered orally (70.2%) or parenterally (29.8%). The mean methotrexate induction dose was 15.3 ± 0.4 mg per week, and the mean duration of therapy was 26.2 months. Of 76 patients who were treated for >6 months, the clinical remission rates were 76.3%, 74.6%, and 80.0% at 6, 12, and 24 months, respectively, by per protocol analysis. The mean CRP levels were 7.5 ± 1.3, 5.3 ± 1.2, 3.8 ± 0.7, and 2.6 ± 0.5 mg/L at 0, 6, 12, and 24 months, respectively. Of 31 patients who underwent follow-up endoscopy after 27.5 months, the endoscopic remission rate was 38.7%. Baseline hemoglobin level < 10 g/dL was a significant independent factor negatively associated with clinical remission at 6 (odds ratio [OR]: 0.023, 95% confidence interval [CI]: 0.003-0.206, p = 0.001) and 12 (OR, 0.079; 95% CI: 0.009-0.699, p = 0.023) months. Parenteral administration was a significant independent factor positively associated with clinical remission (OR: 11.231, 95% CI: 1.027-122.811, p = 0.047) and endoscopic remission (hazard ratio: 4.711, 95% CI: 1.398-15.874, p = 0.012) at 12 months.

Conclusion

Methotrexate monotherapy was effective and tolerable as a maintenance therapy in CD patients.
P762 Risk of Infection After Acute Severe Ulcerative Colitis in East Asia and Australia/New Zealand: AOCC and ANZIBDC collaboration study
Authors: Kim S J , Kim D H , Park S H , Kim K O , Lee Y J , Song E M , Kim E S , Lee H S , An Y K , Begun J , Ruddick-Collins L , Fernandes R , Liu J , Cao Q , Kobayashi T , Wei S C
Published: January 2024

Background

Infection is one of the concerns in the treatment of inflammatory bowel disease, and advanced age and immunosuppressants are known to be risk factors for infection. However, there has been no studies on infection after acute severe ulcerative colitis (ASUC) and its associated factors. The aim of this study was to investigate infection and associated factors in ASUC patients, as well as differences in infection risk between regions of East Asia and Australia/New Zealand (ANZ).

Methods

We retrospectively analyzed patients with ASUC diagnosed according to Truelove Witt criteria from January 2015 to September 2022. We identified the overall incidence of infection and related risk factors, and then analyzed the differences by two regions.

Results

A total of 676 ASUC patients (329 in East ASIA, 347 in ANZ) were enrolled. Overall infections within 1 year after ASUC occurred in 65 patients (9.6%). Clostridioides difficile (C. diff) infection (17/65, 26%), CMV colitis (14/65, 21%), and pneumonia (7/65, 10%) were most common infections. Risk factor associated with infection was combination therapy with anti-TNF agent and thiopurine at discharge (hazard ratio [HR] 5.225, 95% confidential interval [CI] 2.469-11.059, P<0.001). The group with infections exhibited worse outcomes, including a higher readmission rate (39.3% vs. 92.2%, p < 0.001), readmission due to ulcerative colitis (UC) (16.3% vs. 31.3%, p = 0.004), UC-related mortality (0.9% vs. 9.6%, p < 0.001), and overall mortality during the follow-up period (1.1% vs. 13.8%, p < 0.001, Table 1).

In comparative analysis between East Asia and ANZ, there was no difference in the incidence of infection (7.6% vs 11.5%, p=0.083) and infection related mortality (1% vs 0.3%, p=1.000) within 1 year after ASUC. CMV colitis (10/25, 40%) and C. difficile infection (6/25, 24%) were common in East Asia while C.difficile infection (11/40, 27%) and skin infections (7/40 17%) occurred frequently in ANZ. The risk factors for infection in East Asia were anti TNF at discharge (HR 3.684, 95% CI 1.434-9.465, P=0.007) and CMV infection (HR 3.587, 95% CI 1.136-11.333, P=0.03), but the risk factors for infection in ANZ were combination therapy with anti TNF and thiopurine at discharge. (HR 7.911, 95% CI 3.397-11.333, P=<0.001, Figure 1).

Conclusion

The incidence of infection within 1 year after ASUC is 9.6%, and combination therapy of anti-TNF and thiopurine at discharge is a risk factor. Infections were associated with poor prognosis including mortality. There was no difference in the incidence and mortality rates of infections between East Asia and ANZ while the types of infections and related risk factors were different.
P765 A Novel Monoclonal Antibody Drug Candidate SPY001 Targeting Integrin ɑ4β7 for the Treatment of IBD Demonstrates Prolonged Half-Life in Non-Human Primates
Authors: Zhu E , Rios D , Vaz R , Friedman J , Nguyen D , Spencer A , Oh J , Shaheen H
Published: January 2024

Background

Background: Antagonism of the interaction between the cellular adhesion integrin ɑ4β7 and endothelial ligand mucosal addressin cell-adhesion molecule-1 (MAdCAM-1) has proven to be relatively safe and effective in the treatment for Crohn’s disease (CD) and ulcerative colitis (UC). Additional benefit may be gained from an ɑ4β7 antagonist given via the subcutaneous (SC) route at extended intervals (eg, every 8 to 12 weeks) during maintenance therapy.

Methods

The humanized monoclonal IgG1 antibody SPY001 binds to the same ɑ4β7 epitope as vedolizumab and includes a YTE modification within the Fc region to increase its serum half-life via increased affinity for the neonatal Fc receptor (FcRn), thereby favoring recycling into the circulation over degradation. Half-life extension was evaluated via pharmacokinetic analysis in Tg276 transgenic mice (hemizygous for human FcRn) following a single intravenous bolus dose of SPY001 (10 mg/kg, 5 mg/kg, 1 mg/kg) and in cynomolgus monkeys following a single bolus dose of SPY001 (150 mg/kg), given by either intravenous (IV) and subcutaneous (SC) administration. PK simulations in humans were based on allometric scaling of SPY001 clearance observed in cynomolgus monkey and conducted in MATLAB.

Results

In Tg276 mice, the half-life of SPY001 was 10-11 days across all dose cohorts compared to approximately 3 days for vedolizumab. In cynomolgus monkeys, the half-life of SPY001 was 19-23 days following a single IV or SC infusion, a significant increase over the reported half-life of 10 days for vedolizumab in cynomolgus monkeys. Based on allometric scaling of the clearance of SPY001 observed in this study, predictive simulations of SPY001 PK in humans suggested that Q8W-Q12W SC dosing at 300 mg would be able to achieve a C6-wks, induction ≥ 35 mg/mL and Ctrough, ss ≥ 6 mg/mL for simulated patients covering a large range of body weights and albumin concentrations.

Conclusion

SPY001 is a novel humanized monoclonal IgG1 with an extended half-life over that of vedolizumab in Tg276 mice and cynomolgus monkeys. It offers the potential for effective and safe treatment of CD and UC with the advantage of infrequent SC dosing. Further preclinical and clinical studies are warranted to demonstrate this potential.
P788 The effect of etrasimod on faecal calprotectin and high-sensitivity C-reactive protein: Results from the ELEVATE UC clinical programme
Authors: Jairath V , Rubin D T , Verstockt B , Çekin A H , Abreu M T , Lees C W , Fellmann M , Woolcott J C , Crosby C , Wu J , Bhattacharjee A , Herman D , Gu G , Siegmund B
Published: January 2024

Background

Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Here, we present a post hoc analysis of efficacy data from two phase 3 trials, ELEVATE UC 52 and ELEVATE UC 12,1 assessing associations with faecal calprotectin (fCAL) and high-sensitivity C-reactive protein (hsCRP) and responses to etrasimod in patients (pts) with UC.

Methods

In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), pts aged 16–80 years with moderately to severely active UC were randomised 2:1 to etrasimod 2 mg once daily or placebo. Efficacy endpoints of clinical remission, clinical response and endoscopic improvement-histological remission (EIHR) were measured at Wk 12 (both trials analysed separately) and Wk 52 (ELEVATE UC 52). Differences in median fCAL and hsCRP between responders and nonresponders (based on criteria for each endpoint) were assessed. Wilcoxon p values were calculated for responder analyses. Sensitivity and specificity based on fCAL and hsCRP concentrations were presented as receiver operating characteristic (ROC) curves with area under the curve (AUC).

Results

In ELEVATE UC 52 and ELEVATE UC 12, 289 and 238 pts received etrasimod and 144 and 116 received placebo, respectively. Baseline fCAL and hsCRP concentrations were similar across cohorts and levels decreased with etrasimod treatment (median change from baseline at Wk 52 [ELEVATE 52]; -710.56 mg/kg and -0.49 mg/L for fCAL and hsCRP, respectively). Following etrasimod, Wk 12 (both studies) and Wk 52 (ELEVATE UC 52), median fCAL and hsCRP were significantly lower in responders vs nonresponders for all efficacy endpoints (fCAL [ELEVATE UC 52] shown in Table; all endpoints p<0.01). At Wk 4, pts receiving etrasimod who were subsequent responders for efficacy endpoints at Wk 12 had lower median fCAL concentrations vs nonresponders in both trials (all p<0.001; Figure). A similar trend was observed for Wk 4 median fCAL concentrations and responders for efficacy endpoints at Wk 52 (ELEVATE UC 52). Across endpoints in both trials, ROC analyses indicated that both fCAL and hsCRP were consistent in predicting short- and longer-term outcomes, with more pronounced associations at Wk 52.

Conclusion

In phase 3 trials in pts with UC, fCAL and hsCRP levels decreased with etrasimod treatment. ROC analyses indicated association between fCAL and hsCRP and treatment response at all endpoints, and demonstrated significantly lower fCAL and hsCRP values in responders. These data demonstrate the utility of fCAL and hsCRP to predict and monitor disease control in pts with UC treated with etrasimod.

Reference

1. Sandborn WJ et al. Lancet 2023; 401: 1159–1171.
P789 Impact of risk factors for Janus kinase inhibitor use identified by the Pharmacovigilance Risk Assessment Committee on the safety and efficacy of ozanimod in patients with moderately to severely active ulcerative colitis
Authors: Siegmund B , Kuehbacher T , Armuzzi A , Hart A , Bressler B , Feagan B G , Wu H , Ahmad H A , Osterman M T , Charles L , Poehler A M , Jain A , Danese S
Published: January 2024

Background

With the emergence of oral small molecule therapies for ulcerative colitis (UC), there is a need for identification of favourable safety and efficacy profiles for these therapies. The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency reassessed the benefit–risk of Janus kinase inhibitor (JAKi) use based upon data showing increased risk of major adverse cardiovascular (CV) events (MACE) and cancer with tofacitinib. Accordingly, the PRAC identified criteria for which a JAKi should be used only if no alternatives are available or used with caution. This analysis of the phase 3 True North (TN) study (NCT02435992) evaluated the safety and efficacy of ozanimod (OZA) by the presence of JAKi PRAC criteria in patients with moderately to severely active UC.

Methods

Analyses were performed in TN patients comparing those with ≥1 vs no JAKi PRAC criteria at TN baseline (BL). The criteria included age ≥65 y, history of major CV problems, history of CV risk factors (eg, hypertension, high-density lipoprotein cholesterol <40 mg/dl, diabetes mellitus), current or former smoker, and history of cancer. Safety was monitored through Week (W) 52 and efficacy endpoints were assessed at W10 and W52 in patients receiving OZA or placebo (PBO).

Results

At TN BL, 491 patients had ≥1 JAKi PRAC criteria and 521 had no JAKi PRAC criteria. BL patient characteristics were generally similar across groups, but the ≥1 JAKi PRAC criteria group was older (46-48 y vs 36-37 y), with more male patients (62-72% vs 52-61%) and longer UC disease duration (7-9 y vs 6-7 y) vs the no JAKi PRAC criteria group. Treatment-emergent adverse events (TEAEs) occurring during the induction and maintenance periods are shown in Table 1. Overall, TEAE rates were slightly higher in patients with ≥1 vs no JAKi PRAC criteria; however, rates of serious TEAEs and TEAEs leading to treatment discontinuation were similar. Bradycardia and hypertension rates were slightly higher in patients with ≥1 vs no JAKi PRAC criteria; rates of other CV and thromboembolic events and cancer were similar between groups. At W10, OZA was more effective than PBO for clinical remission and response, with slightly greater treatment differences in patients with ≥1 vs no JAKi PRAC criteria (Figure 1A). At W52, more OZA/OZA pts achieved all endpoints vs OZA/PBO pts, with slightly greater treatment differences in patients with ≥1 vs no JAKi PRAC criteria (Figure 1B).

Conclusion

In patients with UC, JAKi PRAC criteria were not associated with greater rates of MACE or cancer with OZA for up to 52 wk, nor did they affect OZA efficacy, suggesting that OZA is a safe and tolerable oral small molecule treatment option for such patients.
P815 Infliximab drug monitoring: proactive or reactive: a North West England NHS 3 trust retrospective study
Authors: Campbell R , Nelson E , Everall J , Ash N , Mountford J , Davies J
Published: January 2024

Background

Therapeutic drug monitoring (TDM) plays a vital role in the management of patients on Infliximab. (1) The British Society of Gastroenterology (BSG) recommends TDM assessment ideally takes place 2-4 weeks after the initial loading doses, however the European Crohns and Colitis Organisation (ECCO) do not make particular proactive or reactive recommendations for TDM. (1,2,3)

Methods

Three North West England NHS trusts retrospectively collected data on 75 patients who had Infliximab trough and antibody levels done within a 12 month time frame. The aim was to establish if collectively TDM was done proactively or reactively and the overall outcomes from the monitoring.

Results

The demographic profile gave us 37 females and 38 males with the disease distribution predominantly Crohns disease ( N=53). There were more participants in the 18-50 age range (N=53) with 22 patients being 31-40 years of age, less participants in the 51-70+ age range ( N=22). Dual therapy with either Mercaptopurine or Azathioprine accounted for 49 out of the 75 participants with a majority favouring Azathioprine. Clinical management and routine use of TDM was seen in 40.5% ( N= 54) of patients indicating proactive use of monitoring in this study. TDM was undertaken after induction and annually in 48 patients whilst the remaining 27 patients received monitoring as ‘maintenance’, this is similar to the BSG recommendations and in a study by Sagar et al in 2021 ( 4).

Conclusion

Although the three participating trusts may use differing assays for the TDM, the outcomes show that it is used proactively for the majority of patients after induction and annually in keeping with BSG recommendations (3). From the data collected a further examination of results regarding subcutaneous versus intravenous TDM outcomes is proposed as the trusts move towards providing patients with both modes of administration of Infliximab.