bluuebunny/crossref_metadata_2025 huggingface dataset:
P0913 Characteristics of patients with very late-onset ulcerative colitis: A single-center retrospective study
Authors: Ito A , kouroku M , Yonezawa M , Tani K , Futatsuki R , Ogawa S , Shigeki Y , Nakai Y
Published: January 2025

Background

Very late-onset ulcerative colitis (UC) has become prevalent in recent years. The differences between very late-onset, late-onset, and early-onset ulcerative colitis have not yet been studied.

Methods

The clinical characteristics, steroid side effects, remission rates, and surgical rates of UC patients were retrospectively studied. Patients were allocated to three groups according to age at diagnosis: very late-onset group (≥ 65 years), late-onset group (50–64 years) and early-onset group (≤ 49 years). Surgery rates, within 1-2 years of diagnosis, were examined in terms of number of cases.

Results

Clinical characteristics such as admission age, duration of disease, history of cancer, days to diagnosis, clinical activity on admission, hemoglobin level on admission, and steroid use were significantly different between the three groups. The adverse effects of steroids were significantly more common in the very late-onset group. The remission induction rate differed significantly between the three groups: early onset, 390 (83.6%); late onset, 84 (71.7%); very late onset, 22 (67.7%).

Significant differences were found in surgery rates within 1-2 years of diagnosis: surgery rates within 1 year of diagnosis, early-onset: 10 cases (3.5%), late-onset: 2 cases (3.4%), very late-onset: 3 cases (14.2%). Surgery rate 2 years after diagnosis, early-onset: 12 cases (4.2%), late-onset: 6 cases (10.3%), very late-onset: 5 cases (23.8%) (P < 0.05) (Figuer1).

Conclusion

In this study, there were no significant differences in the use of non-steroidal medications among the three groups. Our findings indicate that an older age of onset of UC is associated with more steroid side effects, lower remission rates, and a higher rate of surgery within 1–2 years of diagnosis, suggesting that very late-onset UC is more refractory than early-onset UC. We hypothesize that age-related immune changes may explain this finding.
P0919 Correlation between trough levels of risankizumab and clinical and biological remission in patients with moderate to severe Crohn’s disease: a retrospective multicenter study (RISE-CD)
Authors: Sequier L , Altwegg R , Barrau M , Bozon A , Nancey S , Boschetti G , Roblin X , Caillo L
Published: January 2025

Background

Inflammatory bowel disease management has evolved in recent years, with the emergence of new biotherapies such as risankizumab,(RZB) an interleukin (IL) 23 p19 inhibitor, with demonstrated efficacy in moderate-to-severe Crohn’s disease.

While the relationship between trough levels and clinical remission is well established for anti-TNF alpha agents, it has yet to be demonstrated for new molecules of interest. The aim of this study was to investigate the correlation between RZB trough levels and clinical and biological remission at 6, 12 and 18 months.

Methods

This retrospective multicenter study included patients with moderate-to-severe Crohn’s disease from 4 centers, who were being treated with RZB after failure of all other approved biotherapy lines. Clinical activity, assessed by the Harvey-Bradshaw Index (HBI) and biological activity with CRP and fecal calprotectin, as well as serum RZB levels by Elisa technique (Biosynex) were collected. The primary endpoint was clinical and biological remission at 12 months, defined as HBI < 4, CRP < 5 mg/L and fecal calprotectin < 250 µg/g of stool. Secondary objectives were the correlation between RZB levels and clinical and biological remission at 6 and 18 months, treatment persistence, and safety.

Results

Overall, 43 patients were included in 4 centers. Most patients had ileocolic Crohn’s disease (44.7%), 50% had ano-perineal lesions, 23.7% had extra-intestinal manifestations and 71.7% had a history of bowel resection. Six patients (15.8%) were receiving a combination of advanced therapies with upadacitinib or golimumab. At 12 months, 30.2% of patients were in clinical and biological remission (n=13) and had significantly higher RZB trough levels than patients who were not in remission (8.26 ± 4.66 vs. 4.44 ± 2.37 respectively; p=0.002). The ROC curve identified an optimal risankizumab trough levels threshold of 7.7 µg/mL for predicting clinical and biological remission at 12 months (sensitivity 61.5%; specificity 92%). At 6 and 18 months, 11.7% (n=5) and 34.9% (n=15) of patients were in clinical remission and had significantly higher RZB trough levels. At 6 months, 12 months and 18 months, 43 (100%), 38 (88.4%) and 31 (72%) patients were still on RZB. No patient developed anti-risankizumab antibodies.

Conclusion

In our multicenter study, with the largest number of patients analyzed to date, trough levels of risankizumab were correlated with clinical and biological response at 12 months in patients with moderate-to-severe Crohn’s disease, in line with data from previous single-center studies but larger prospective studies are still needed.
P0923 Impact of Inflammatory Bowel Disease on Women’s Health
Authors: Bhardwaj A , Singh D M A , Sharma R , Bansal N , Singh D , Midha V , Sood A
Published: January 2025

Background

Inflammatory bowel disease presents chronic challenges that disrupt physical well-being and create significant psychosocial stressors. Despite known gender-specific issues, data on how IBD affects women, particularly in a socio-cultural context, remain limited.

Methods

We conducted a cross-sectional study with 202 women diagnosed with IBD, recruited from a tertiary care center in north India. Participants were subjected to a structured questionnaire covering health domains influenced by IBD, including menstrual and reproductive health, sexual function, social dynamics, mental health, financial burdens, and access to healthcare services in a face-to-face interview.

Results

The median age of participants was 41 years, with a median disease duration of 5 years. Menstrual irregularities were reported by 50%, and 57% females experienced severe menstrual pain. Among sexually active participants, 82.5% showed signs of sexual dysfunction. Reproductive concerns were prevalent, with 55.4% worried about heritability, while only 2.5% received guidance on cervical cancer screening. The median SICC-IBD score of 0.6 (0.4-0.6) indicated substantial social impacts, with family and societal stigma reported by 43% of participants, leading to strained relationships and decreased quality of life. Financial concerns were notable, with nearly 25% of monthly income being spent on IBD medications. Mental health concerns were significant; 95% reported moderate-severe stress, and 70% had symptoms suggestive of moderate to severe anxiety or depression. (Figure 1)

Conclusion

IBD significantly impacts the lives of women beyond clinical symptoms, affecting menstrual, sexual, and reproductive health, and exacerbating social, mental, and financial strains. Limited access to healthcare support and social stigmatization further complicate disease management. Addressing these unique challenges requires holistic and multidisciplinary interventions that incorporate reproductive health counseling, mental health support, and tailored socio-cultural interventions to improve the overall well-being of women with IBD. This study underscores the need for gender-specific approaches in managing IBD in resource-limited settings.
P0924 Efficacy and Safety Assessment of Ustekinumab in Postoperative Crohn’s Disease Patients in China
Authors: Xianzong M , Jia Y , Linyan Z , Xinmei Z , Xingzhao H , Ling L , Xuchun Z , Feng T
Published: January 2025

Background

Crohn’s disease (CD) poses a significant risk of postoperative recurrence (POR), complicating management, and data on the use of Ustekinumab (UST) in postoperative CD patients in China is limited. This study evaluated the efficacy and safety of UST in preventing POR.

Methods

This multicenter, retrospective observational study involved postoperative CD patients from four Chinese tertiary hospitals, all of whom had at least two high-risk recurrence factors. Patients who failed anti-TNF-α treatments or Vedolizumab switched to UST as non-first-line therapy, while others received UST as first-line treatment at least two weeks post-surgery. Efficacy was evaluated using endoscopic success (Rutgeerts score) and clinical disease activity (Harvey-Bradshaw Index [HBI]), with safety determined by adverse events after a minimum follow-up of 24 weeks.

Results

This study included 53 patients with a mean age of 36.8 years. Significant improvement in the Rutgeerts score was observed (p < 0.001). The remission rate (i0) increased from 0.0% to 32.1% post-treatment. Notable changes were seen in i1 (from 5.7% to 32.1%) and i2 (from 49.1% to 28.3%), while severe disease cases (i3 and i4) declined significantly. Overall, the endoscopic success rate was 83.0%. Similarly, the HBI score significantly improved (mean ± SD: 6.1 ± 2.5 before vs. 2.4 ± 1.7 after, p < 0.001). The median HBI decreased from 6.0 to 2.0, with remission rates rising from 18.9% to 90.6%, while active disease cases fell from 81.1% to 9.4% (p < 0.001). The percent of 90.3 in the first-line group experienced a decrease in their Rutgeerts score, compared to 72.7% in the second-line group, though this difference was also not statistically significant (p = 0.093). A significant difference was noted in HBI scores (p = 0.016), with the first-line group’s mean at 1.9 ± 1.3 being significantly lower than the second-line group’s 3.1 ± 1.9. The median HBI followed this trend, with values of 2.0 for the first-line and 3.0 for the second-line group. The mean BMI increased from 19.9 ± 3.8 to 21.1 ± 3.7, though not significantly (p = 0.078). Nutritional status improved, as indicated by increased mean albumin (41.3 ± 15.2 vs. 43.7 ± 15.3, P = 0.043) and hemoglobin levels (116.6 ± 24.9 vs. 125.9 ± 23.9, P = 0.019). Only one adverse event, secondary kidney function impairment, was reported.

Conclusion

UST exhibited significant efficacy in preventing POR of CD with a favorable safety profile, whether used as a first-line or non-first-line treatment. Our research provided essential evidence from an Eastern population regarding the effectiveness and safety of UST in postoperative CD patients.

References

Torres J, Bonovas S, Doherty G, et al. ECCO Guidelines on Therapeutics in Crohn’s Disease: Medical Treatment. J Crohns Colitis. 2020. 14(1): 4-22.
P0926 The impact of anti-integrin αvβ6 antibody positivity on clinical characteristics and treatment outcomes with biological agents in pediatric IBD: a single-center retrospective study
Authors: Oue H , Takeuchi I , Hiejima E , Tanioka A , Komorizono R , Maeda Y , Nihira H , Shiokawa M , Shimizu H , Arai K
Published: January 2025

Background

Anti-integrin αvβ6 antibody (V6Ab) has emerged as a promising diagnostic marker for differentiating ulcerative colitis (UC) from Crohn’s disease (CD) in adult. However, approximately 30% of pediatric-onset CD cases reportedly exhibited V6Ab positivity. The impact of V6Ab on the clinical characteristics and treatment response of pediatric inflammatory bowel disease (IBD) remains unknown. This retrospective single-center study aimed to investigate the clinical characteristics and relevance of V6Ab in pediatric IBD as a pilot study.

Methods

We retrospectively reviewed the records of 60 children with IBD whose V6Ab status was measured (V6Ab+CD: 22 cases, V6Ab-CD: 17 cases, V6Ab+UC: 18 cases, V6Ab-UC: 3 cases). Associations between V6Ab and reclassification of diagnosis, perianal lesions, endoscopic and clinical activity scores, and anti-TNF failure were analyzed. V6Ab positivity was defined as an optical density (O.D.) >0.2525 at 450 nm. Clinical remission was determined by a weighted Pediatric Crohn’s Disease Activity Index (wPCDAI) ≤2, while endoscopic remission was based on a Simple Endoscopic Score for Crohn’s Disease (SES-CD) ≤2. Anti-TNF failure referred to discontinuation due to insufficient efficacy, excluding cases related to side effects.

Results

13 V6Ab+CD cases were initially diagnosed as UC and later reclassified to CD based on the revised-Porto criteria. The prevalence of perianal lesions was significantly lower in V6Ab+CD compared to V6Ab-CD (3/22 vs 11/18, respectively, p<0.05). Furthermore, UC-like colonic findings, such as granular mucosa and loss of vascular pattern, were significantly more common in V6Ab+CD than in V6Ab-CD (22/22 vs 3/18, respectively, p<0.05). Anti-TNF failure occurred in 10/17 V6Ab+CD cases was significantly higher than that in UC (1/9, p<0.05) but comparable to V6Ab-CD (8/13, p>0.99). Among CD cases treated with ustekinumab (UST) following anti-TNF failure, V6Ab+CD demonstrated a significantly higher endoscopic remission rate (5/7) compared to V6Ab-CD (0/6, p<0.05), even though clinical remission rates did not differ significantly between the groups. (7/7 vs 5/6, respectively, p<0.05)

Conclusion

V6Ab+CD cases may have a higher risk of anti-TNF failure compared to V6Ab+UC. Additionally, ustekinumab (UST) appears to be effective for V6Ab+CD patients who experience TNF failure. These findings suggest the potential of V6Ab as a valuable biomarker for precision medicine. Further analyses from ongoing multi-center prospective studies in Japan are eagerly awaited.
P0928 Patient endotypes in ulcerative colitis revealed by longitudinal symptom trajectories under therapy
Authors: El Houjjaji C , Paun A , McBride J , Schreiber S , Mueller-Breckenridge A J
Published: January 2025

Background

Ulcerative colitis (UC) poses unique challenges in patient care. Although therapies have led to better outcomes, only 20-30% of patients enter remission, and even fewer sustain it over time. A critical need remains in addressing three key areas: i) predicting which patients will enter remission, ii) tailoring treatments to individual patient needs, and iii) identifying novel therapeutic targets that can sustain long-term remission. Symptom trajectories under therapy offer an accessible approach to addressing these challenges and this work investigates their alignment with molecular responses to assess their clinical value.

Methods

Using a reverse translation approach, this study analyses longitudinal data from the etrolizumab phase 3 trials to gain insights into the UC patient population. Symptom response trajectories of 437 UC patients were tracked over 54 to 66 weeks using the partial Mayo Clinical Score (pMCS). Through unsupervised clustering of pMCS, we identified distinct subpopulations based on their patterns of disease activity. Clinical outcomes within these clusters were then examined, allowing us to uncover significant predictors of rapid and sustained remission. Molecular profiling using gene expression data was then performed, revealing the biological mechanisms that differentiate these patient groups and providing insights into their treatment responses.

Results

Our analysis revealed five distinct patterns of disease response and progression, from patients achieving rapid and deep remission to those with persistently high disease activity. These five symptom-based subgroups match closely with traditional clinical endpoints. We found that predictors of sustained remission, such as elevated albumin levels, low endoscopic scores, and reduced markers of inflammation (faecal calprotectin and C-reactive protein) aligned with these subgroups. In addition, molecular profiling highlighted specific differences in gene expression and immune cell activity, notably showing that patients with deep remission had an enrichment of anti-inflammatory signalling pathways, suggesting a biological basis for their favourable outcomes.

Conclusion

Longitudinal monitoring of symptom trajectories offers a non-invasive, easily measured and reliable proxy for early assessment of the likelihood of achieving deep, sustained remission in UC patients. These symptom patterns show strong concordance with endoscopic, laboratory, and molecular remission profiles. This approach aligns with the principles of personalised medicine by enabling i) dynamic symptom monitoring ii) application in Phase II trials to guide drug development by assessing if a patient is on the right path toward therapeutic success and iii) identification of novel therapeutic targets.
P0931 Induction treatment with upadacitinib is associated with high rate of clinical response in patients with refractory Inflammatory Bowel Disease
Authors: Kitsou V , Ioannou A , Kokkotis G , Chalakatevaki K , Laoudi E , Leonidakis G , Michopoulos S , Zampeli E , Bamias G
Published: January 2025

Background

Upadacitinib is an oral selective Janus kinase-1 (JAK1) inhibitor, that has been approved for the treatment of moderate to severe Ulcerative Colitis (UC) and Crohn’s Disease (CD). The recommended induction dose is 45 mg once daily for 8 weeks for UC and 12 weeks for CD, followed, thereafter, by a maintenance dose of 15 mg or 30mg (for patients with refractory, severe or extensive disease). Our study aims to capture the experience of two tertiary centers on upadacitinib use in refractory UC and CD.

Methods

This is an ongoing, prospective cohort study. Demographic and disease-related data were collected at baseline. Our primary endpoint is clinical response (CR) at the end of induction, defined as >50% decrease in Patient Reported Outcomes (PROs) and secondary endpoints were steroid-free clinical remission (sf-CRem) and treatment persistence. SPSS23 was used for the statistical analysis.

Results

The baseline characteristics of our patients are presented in Table 1. At drug initiation, 35.4% were receiving concomitant corticosteroids. The induction period has been concluded by 23/26 patients with UC and 17/21 patients with CD, of whom 22 (95.7%) and 13 (76.5%) respectively commenced maintenance treatment. The primary endpoint of CR was achieved by 19 out of 20 (95%) patients with clinically active UC and 11 out of 16 (68.8%) patients with clinically active CD at baseline. Sf-CRem was achieved by 21/23 (91.3%) patients with UC and 13/17 (76.5%) with CD. The majority of patients with either UC (86.4%) or CD (84.6%) commenced maintenance therapy with a 30 mg dose. Adverse events occurred in 22.9% of patients in our cohort, with acne being the most frequently reported (12.5%). One patient (2.1%) experienced herpes simplex infection and two (4.2%) an increase in their lipid levels, requiring initiation of antihyperlipidemic therapy. No serious adverse events have been reported.

Conclusion

In our cohort of patients with Inflammatory Bowel Disease who were refractory to multiple advanced treatments, upadacitinib has been shown to be an effective and safe therapeutic option for induction of remission. Most patients with medically refractory IBD in our cohort have received increased maintenance Upadacitinib dosage.
P0935 A systematic review and quality assessment of clinical practice nursing guidelines for ostomy care
Authors: Hutton M , Prins H , Yuan Y , Solitano V , Radford S , Vuyyuru S K , Rieder F , Jairath V
Published: January 2025

Background

Patients living with stomas face numerous challenges following abdominal stoma surgery. Stoma nurse specialists play a crucial role in supporting these patients by utilizing evidence-based practices and specialist expertise. We evaluate nursing guidelines focused on the management of patients with ostomies, identify knowledge gaps, and support the development of evidence-based patient care pathways.

Methods

A comprehensive literature search was conducted across MEDLINE, Embase, and major nursing organization websites up to March 25 2024, to identify evidence-based practical guidelines developed specifically for nurses managing patients with abdominal stomas post-ostomy. Pre-specified inclusion (n=5) and exclusion (n=16) criteria were applied (Table 1). Two researchers independently screened references, extracted data, summarized the evidence, and assessed guideline quality using the AGREE II instrument.

Results

The database search yielded 97 references, with an additional 23 guidelines identified through major nursing organization websites. A total of 14 nursing guidelines met the inclusion criteria, originated from Australia, Canada, Italy, UK, USA, and three international groups. The guidelines varied in scope; offered recommendations across all stages of care, including preoperative, peri-operative, postoperative, and post-discharge phases. Key topics are presented in Table 2. Notably, no guideline statements specifically addressed patients with Crohn’s disease and permanent ostomies.

Three guidelines did not specify whether a literature search and review were conducted. Five guidelines applied an evidence scale or numerical grading system, while only three used the GRADE approach. Most recommendations were based on a low level of evidence, often relying on retrospective or observational studies and expert opinion; two guidelines claimed their statements were consensus-based due to a lack of supporting evidence. In the AGREE II assessment, most guidelines were rated as moderate quality, with recommended modifications primarily in the rigor of development and applicability.

Conclusion

This quality assessment of clinical practice nursing guidelines for ostomy care highlights both strengths and weaknesses within current guidelines. Nursing guidelines offer extensive coverage of ostomy care topics and provide valuable first-line care experience and consensus statements, particularly for postoperative stoma and peristomal care. These insights are essential for non-nursing healthcare providers and contribute to the development of patient care pathways for individuals with Crohn’s disease and permanent ileostomies. However, the limited availability of high-quality evidence underscores the need for further research in ostomy care.
P0941 Questionnaire survey of Japanese patients with inflammatory bowel disease and physicians on shared decision making in advanced therapy: A web-based PAIR survey
Authors: Imai K , Hirai F , Matsumoto T , Goda Y , Fujimitsu Y , Kajioka T , Oiwa M , Honjo T , Higashikawa M , Ueno M
Published: January 2025

Background

With the recent increase in available treatment options for inflammatory bowel disease (IBD), shared decision-making (SDM) has gained considerable importance. To address potential disparities in patient and physician priorities, we conducted a survey for clarify these perspectives.

Methods

Patients with IBD and physicians treating IBD were asked to complete an online questionnaire focused on key factors influencing drug selection and preferred drug administration methods.

Results

Responses were obtained from 400 patients (327 with ulcerative colitis and 73 with Crohn’s disease) and 155 physicians. Among the factors in drug selection, physicians assigned significantly higher importance scores for experience with the drug than did patients. The expected time-to-onset of drug effects was significantly different between patients and physicians. Regarding preferences for drug administration method, patients and physicians assigned the highest acceptability scores for once-daily oral administration. For intravenous and subcutaneous routes, patients’ scores were significantly lower than those of physicians’ scores. Notably, 86.0% of patients and 62.0% of physicians preferred oral administration as the most preferred method. However, preferences varied based on treatment experience: 34.7% of patients with prior experience with subcutaneous injection preferred this method.

Conclusion

Patients and physicians generally shared similar priorities for drug selection; however, physicians emphasized their experience with the drug over patient preferences. Although the number of patients with prior treatment experience preferred intravenous or subcutaneous injections, oral formulations remained the preferred choice for both patients and physicians.
P0945 Improvement in Endoscopic Score in Patients with Moderately to Severely Active UC Treated with Risankizumab in the Phase 3 INSPIRE and COMMAND Studies
Authors: Panaccione R , Verstockt B , Hashash J G , Shah S , Morisset P , Kalabic J , Reguiero M
Published: January 2025

Background

The STRIDE-II recommendations highlighted the importance of targeting objective measures of disease control, including endoscopic healing, in patients (pts) with ulcerative colitis (UC).1 Risankizumab (RZB), an interleukin-23 specific inhibitor, showed improvement in the outcomes of clinical remission and endoscopic improvement compared to placebo in pts with moderately-to-severely active UC.2 Visualizing the changes of endoscopic scores from induction and maintenance may provide insight into pt disease course during treatment. Thus, this analysis sought to provide an overview of change in endoscopic scores of pts enrolled in UC clinical studies.

Methods

Using individual pt data from the Phase 2b/3 studies of RZB in UC, changes in Mayo endoscopic scores in induction and maintenance were assessed. For induction, pts received either intravenous (IV) placebo (PBO) or RZB for 12 weeks (wks). Pts from the Phase 2b and Phase 3 INSPIRE studies who had a clinical response to induction treatment were rerandomized into the maintenance study [COMMAND] and received subcutaneous PBO (withdrawal), RZB 180 mg, or RZB 360 mg every 8 wks for 52 wks. To be eligible for INSPIRE, pts had to have a baseline (BL) Mayo endoscopic score of 3 or 2 confirmed by central review. For this analysis, endoscopic scores are reported for induction BL and wk 12 and maintenance BL and wk 52 for each treatment. "Endoscopic improvement" was defined as a score of 1 or 0 at the time of follow-up.

Results

Among pts with a Mayo endoscopic score of 3 at induction BL, 28% achieved endoscopic improvement after 12-wk treatment with RZB 1200 mg; 57% of pts with a BL score of 2 showed endoscopic improvement (Fig. 1). In contrast, among PBO-treated pts with a score of 3 or 2 at BL, 11% and 18%, respectively, achieved endoscopic improvement after induction. Most PBO-treated pts (63%) had no score change at wk 12. During the maintenance study, 29%–35% of pts in the RZB treatment groups had an endoscopic score of 2 or 3 at maintenance BL. (Fig. 2). For those with a BL score of 3, most pts receiving RZB 360 mg achieved endoscopic improvement (62%); similarly, 65% of those with a BL score of 2 showed endoscopic improvement at wk 52. Trends were similar for RZB 180 mg with ≥80% of pts with a BL score of 1 or 0 maintained a 1 or 0 through wk 52. Among PBO-treated pts, ≥60% maintained a score of 3 or 2 from maintenance BL to wk 52; approximately one third of pts’ scores improved to 1 or 0.

Conclusion

This analysis showed that RZB treatment improved endoscopic outcomes from wk 0 to wk 12 of induction and wk 0 to wk 52 of maintenance. These findings may help inform treatment expectations and shared decision-making for pts with UC initiating RZB treatment.

References

1.Turner D, et al. Gastroenterology. 2021;160(5):1570-1583.

2.Louis E, et al. JAMA. 2024;332(11):881-897.
P0947 A switch to infliximab may be more effective than ustekinumab following adalimumab pharmacodynamic failure in pediatric patients with Crohn’s disease
Authors: Driban G , Matar M , Lev-Tzion R , Ledder O , Granot M , Yerushalmy-Feler A , Magen-Rimon R , Zifman E , Turner D , Assa A
Published: January 2025

Background

Loss of response (LOR) to first biologic agent is not uncommon. One of the most challenging mechanisms of LOR is pharmacodynamic LOR (inflammatory activity in the presence of adequate trough concentrations, TC). We aimed to explore the outcomes of pediatric patients with Crohn’s disease following adalimumab pharmacodynamic failure.

Methods

We conducted a retrospective longitudinal cohort study in 6 Israeli pediatric centers. Data of patients who experienced adalimumab LOR (as first biologic agent) with adequate TC (>7.5 mcg/ml) and switched to either infliximab or ustekinumab were retrieved.

Results

The cohort included 67 patients (66% males, mean age at diagnosis 12.2±2.8, B2 or B3 phenotype 16%, perianal disease 24%), with median duration on adalimumab of 17 (IQR 8-24) months and follow-up of 13 months (IQR 7-29) on the subsequent therapy. Median adalimumab TC before switching was 11.4 (IQR 8.5-16 mcg/ml). For the overall cohort, corticosteroid-free clinical remission and response were achieved in 43% and 67%, respectively. Of 36 follow-up colonoscopies, 25% achieved endoscopic remission. Most patients (84%) received intensified regimen after switching. Nine patients (13%) underwent surgical resection during follow-up. The two treatment groups (infliximab (n=32) and ustekinumab (n=35)) were comparable for all basic, demographic and disease severity parameters at the time of switching. The median follow-up period of both groups was similar, 12 (6-24) months. The infliximab group demonstrated better outcomes over ustekinumab at the end of follow-up in terms of clinical response (97% vs. 57%; p<0.001), corticosteroid-free clinical remission (56% vs. 31%; p=0.04), endoscopic response (83% vs. 28%; p=0.002), fecal calprotectin<250 (60% vs. 27%; p=0.03), drug sustainability (91% vs. 31%; p<0.001) and surgical rate (3% vs. 23%; p=0.02, 1 infliximab, 8 ustekinumab). Month 3 PCDAI was significantly lower [8.7 (IQR 0-17.5) vs. 21 (IQR 9-35); p<0.01), CRP remission was higher (60% vs. 23%; p=0.01) and median albumin concentration was higher [4.3 (IQR 39-4.5) vs. 3.8 (IQR 3.4-4); p=0.005] in the infliximab group.

Conclusion

Pediatric patients with Crohn’s disease following adalimumab pharmacodynamic failure with TL>7.5mcg/mL demonstrated moderate response to subsequent therapy. A switch in-class to infliximab may be more effective than a switch out of class to ustekinumab.
P0949 Long term real-world effectiveness and safety of upadacitinib in patients with moderate to severe Crohn’s disease: A Belgian multi-centric refractory cohort
Authors: Pavlidi A , Verstockt B , Vieujean S , Desmedt V , Couturier F , Rahier J F , Baert F , Somers M , Dewit O , Bossuyt P , Hoyois A , Holvoet T , Ouziel R , Willandt B , Lambrecht G , Salame M , Verreth A , Lenfant M , Franchimont D , Cremer A
Published: January 2025

Background

The therapeutic options for Inflammatory Bowel Disease (IBD) have expanded with the introduction of JAK inhibitors. However, real-world data on upadacitinib (UPA) in patients with moderate to severe Crohn’s disease (CD) are scarce. Our aim was to assess the long-term effectiveness and safety of UPA in multi-refractory Belgian patients.

Methods

Data from all patients with active CD initiating UPA between September 2022 and January 2024 were retrospectively collected from 17 Belgian centres. Effectiveness endpoints were evaluated at week 24 and 52. Steroid-free clinical response and remission were defined using the two-component patient-reported outcome. Endoscopic response was defined as a decrease in baseline Simple Endoscopic Score (SES-CD) with ≥50%, and endoscopic remission as SES- CD ≤ 4 or absence of ulcers. Adverse events (AE), treatment discontinuation, CD-related hospitalization and surgery were assessed throughout follow-up. Non-response imputation was applied for clinical evaluation.

Results

A total of 140 patients were included (Table 1) with a median follow-up of 33 weeks (IQR: 3-97). The majority of patients (89%) were exposed to at least 3 biologics. At week 24, 53% and 40% of patients achieved steroid-free clinical response and remission, respectively (Figure 1). At week 52, these numbers were 37% and 29%. Endoscopic data were available in 48/140 patients at week 24, of whom 52% and 27% reached endoscopic response and remission. At week 52, these numbers were 63% and 37%. Of patients with active articular extra-intestinal manifestations at baseline 37% and 34% had a quiescent articular disease by week 24 and 52, respectively. 5 out of 9 patients with active perianal disease at baseline and on UPA by week 52, had persistent perianal active disease. Overall, 66 patients (47%) discontinued UPA during follow-up: 23 due to primary non response, 13 due to secondary loss of response, 16 due to AE, 3 due to patient’s choice and 11 due to CD-related surgery. 16 patients required CD-related hospitalization within 52 weeks. AE occurred in 60% of patients (84/140). Of these patients, 11% experienced serious AE of which 2 cardiovascular events: 1 transit ischemic attack and 1 deep venous thrombosis. The most common reported AE were herpes simplex reactivation (5/140), respiratory tract infection (7/140), cutaneous reactions (7/140) and acne (17/140). Only 3 patients had reactivation of herpes zoster infection.

Conclusion

In this real-world cohort of highly refractory CD patients, UPA effectively induced both steroid-free clinical remission and endoscopic remission by week 52. UPA was relatively well tolerated with respect to adverse events.
P0954 Food-related quality of life and dietary choices are associated with disease activity in patients with inflammatory bowel disease
Authors: Døssing A S Y , Bager P , Julsgaard M , Borre M , Whelan K , Hvas C L , Rud C L
Published: January 2025

Background

Food-related quality of life (FRQoL) is the enjoyment experienced from the psychosocial aspects of eating and drinking. FRQoL may be altered in patients with inflammatory bowel disease (IBD). Meanwhile, patients often change their diet following their diagnosis. We aimed to describe FRQoL and dietary choices in patients with IBD using validated questionnaires and identify potential predictors of impaired FRQoL.

Methods

This was a cross-sectional, single-centre survey. The FR-QoL-291 and dietary belief2 questionnaires were forward-backwards translated from English into Danish, face-validated and pilot-tested. The translated questionnaires were included in an online survey, in addition to other questionnaires on health-related QoL, fatigue, and diet. The questionnaires were distributed to all adult patients with proven IBD at Aarhus University Hospital, Denmark.

Results

Of 2,655 invitees, 1,262 patients (47.5%) responded. Of the responders, 37.6% had Crohn’s disease (CD), and 60.2% were women. Median (IQR) age was 46 (32-61) years, and median duration since diagnosis was 11 (5-22) years. Mean [95% CI] FR-QoL-29 score was 103.8 [102.2 – 105.4], and it was lower in women than men (-6.5 [-3.3 – -9.8] p<0.001) and lower in CD than ulcerative colitis (-3.7 [-0.4 – -7.0], p=0.027), indicating impaired FRQoL (Figure 1). The patients with IBD in Denmark had considerably higher FR-QoL-29 scores than patients with IBD in the UK (+23 [21 – 25], p<0.001). FR-QoL-29 scores were statistically significantly inversely correlated with disease activity but not with age, years with IBD, medication use, living status, or diet form. Since their IBD diagnosis, 42% of responders had changed their diet, 28.4% believed that diet could be the cause of IBD, and 59.6% believed that their diet could cause a relapse in their disease. Nearly half (46.7%) avoided specific foods to prevent a relapse, and FR-QoL-29 was lower in this group compared with those who did not avoid specific foods (-27.8 [-25.0 – -30.7], p<0.001). Forty-seven per cent reported that certain foods worsen symptoms during a relapse, and 18.2% reported that certain foods may help reduce symptoms during a relapse. Three-quarters (74.9%) took dietary supplements such as vitamins.

Conclusion

Current disease severity and recent relapse are associated with reduced FRQoL in patients with IBD. Controlled trials are needed to investigate whether dietary modifications can help alleviate symptoms during IBD flares, improve FRQoL, and potentially reduce the risk of future flares.

References

1.Whelan K, Murrells T, Morgan M, et al. Food-related quality of life is impaired in inflammatory bowel disease and associated with reduced intake of key nutrients. Am J Clin Nutr. 2021;113(4):832-844.

2.Limdi JK, Aggarwal D, McLaughlin JT. Dietary Practices and Beliefs in Patients with Inflammatory Bowel Disease. Inflamm Bowel Dis. 2016;22(1):164-170.
P0961 Establishing a new cellular therapy for patients with Ulcerative Colitis
Authors: Skov J , Filidou E , Clement D L , Børsch A S , Steenholdt C , Maimets M , Jensen K B
Published: January 2025

Background

Inflammatory Bowel Diseases (IBD), which include Crohn’s Disease and Ulcerative Colitis (UC), show an accelerated incidence rate, affecting up to 1% in Western countries, and an increased burden in healthcare costs, reaching up to 5.6 billion euros per year. Although there are several treatment options, the remission rates are around 30-60%, with primary non-response and loss of response to be the main reasons for changing treatment plans. Thus, there is a need for new therapeutic strategies targeting these groups of non-responding patients. Towards this, we are developing a novel cellular therapy for UC, using autologous transplantation of intestinal epithelial organoids.

Methods

Here, colonic epithelial cells will be isolated, expanded under GMP conditions, and transplanted into ulcerated colonic regions of patients with UC, to promote and accelerate mucosal healing. This initial strategy targets patients with localized ulceration unresponsive to first- and second-lines of treatments.

Results

We have established a robust protocol for expanding intestinal epithelial organoids. These organoids contain all major cell type populations that orchestrate the intestinal epithelium. We have successfully transplanted both murine and human colonic organoids into NOG mice. After successful engraftment onto the damaged intestinal mucosa, they promote and accelerate mucosal healing. Currently, we are establishing scale-up culturing methodologies, in order to expand our cell cultures to a number of cells that would be enough to promote mucosal healing during transplantation in humans. Finally, we are refining the cell culture conditions to be GMP-approved, and thus, registering our final product as acceptable to be used during human clinical trials.

Conclusion

Our approach could offer a new therapeutic option for patients with UC that do not respond to current drug regimens and are in need for an effective treatment.
P0962 Relationship between Total Corticosteroid Dose Prior to Advanced Therapy Induction and Primary Non-Response
Authors: Yokoo T , Yoshikawa S , Masuda T , Terauchi S , Uchida H , Nakao T , Inagaki M , Tani T , Okamoto K , Shibata Y , Inatsugi N
Published: January 2025

Background

The PROFILE study1) highlighted the importance of top-down treatment with Advanced Therapy (AT) in Crohn’s disease. In ulcerative colitis (UC), the corticosteroid (CS) treatment cascade remains crucial for selecting AT candidates. CS treatment efficacy decreases with repeated use, affecting therapeutic outcomes of GMA and carotegrast. We hypothesized that total CS dose impacts subsequent AT efficacy and examined this relationship to optimize AT induction timing.

Methods

We retrospectively reviewed medical records of UC patients diagnosed after January 2010, analyzing the correlation between total CS dose prior to initial AT administration and AT response. Patients using steroids for other diseases or with incomplete CS dose information were excluded. Variables assessed included onset age, sex, disease extent, activity (PRO2), treatment details, and treatment failure rates. Nominal variables were analyzed using Fisher’s exact test and logistic regression analysis.

Results

Data from 92 UC patients (44 males) were analyzed. Median onset age was 41.5 years, with median AT induction age of 46.5 years. Disease extent: total colitis/left-sided/rectum = 57/33/2. Mean total CS dose before AT initiation was 1,743.2 mg, with a mean 479.1 days between CS initiation and AT start. AT breakdown: IFX/ADA/GLM/VDZ/UST/UPA/TOF/FIL = 37/19/13/13/6/2/1/1. Median PRO2 at AT initiation was 4. (TABLE 1)

Primary non-response (PNR) occurred in 23 cases (24.0%), and loss of response (LOR) in 18 cases (18.8%). Multivariate analysis identified total CS dose ≥3,000 mg as a significant risk factor for PNR (OR 4.21, 95%CI 1.32-13.5, p=0.02). (TABLE 2) No risk factors were identified for LOR.

Conclusion

As previously reported, elderly-onset UC requires careful management due to potentially poor treatment response. The total CS dose appears to significantly impact primary non-response, suggesting that early transition to Advanced Therapy may be crucial for optimal patient outcomes.

References

1)Nurulamin MN. A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn’s disease (PROFILE). Lancet Gastroenterol Hepatol. 2024;9(5):415-427 doi:10.1016/S2468-1253(24)00034-7
P0964 The effect of alarms on completion of electronic diaries in patients with inflammatory bowel disease
Authors: Kusanto B , Visser M , Wandare N , Capece A , Lee E , Byrom B , Everhart A
Published: January 2025

Background

Clinical trials have contributed substantially to the development of novel therapies for inflammatory bowel disease, including Crohn’s disease (CD) and ulcerative colitis (UC). The Food and Drug Administration (FDA) recommends the use of the Crohn’s Disease and Activity Index (CDAI) and the modified Mayo Score (mMS) to measure primary endpoints in CD and UC trials, respectively. Both assessments use composite scores requiring the completion of a daily diary by subjects to report on symptoms, including stool frequency (SF), rectal bleeding, abdominal pain, and general well-being. In order to ensure the timely completion of diaries, and to limit missing days, it has been recommended to implement device alarms or reminders. The objective of this study was to investigate how device alarms and/or reminders can influence completion times of the daily electronic diaries (eDiaries) in CD and UC studies.

Methods

More than 3.7 million eDiary entries from 12 153 patients across 11 studies in CD and UC were evaluated. Only completed entries were included. Patients were required to complete eDiaries daily, either on their personal device or a provisioned device, throughout their participation in a specific study. Daily alarms were programmed to remind patients to complete their eDiary. For this analysis, the difference between the patient’s eDiary alarm time and the time the eDiary was first opened was determined.

Results

For CD trials, 65% (n=1 079 823) of eDiaries were opened after the programmed alarm time. Of these eDiary entries, 39% (n=652 138) were answered 30 minutes after the alarm time, and 8% (n=127 711) were answered between 30 minutes and an hour after the alarm time. In UC trials, 60% (n=1 277 090) of eDiaries were opened after the programmed alarm time. Similarly, 38% (n=822 552) of eDiaries were completed after 30 minutes of the alarm time, and 8% (n=170 433) were completed between 30 minutes and an hour after the alarm time.

Conclusion

The implementation of eDiary alarms is essential to support patient compliance in clinical trials and drive reliable inferences. The analysis performed here suggests that eDiary alarms are useful to encourage patients to answer their eDiary within an hour reporting window of their scheduled alarm time. Nevertheless, sites and study teams should continue to educate patients on the importance of eDiary completion.
P0965 Sequencing Therapy for Optimal Response in Mirikizumab (STORM) Study
Authors: Kubesch A , Lande R , Farrag K , Dienethal A , Sprinzl K , Zeuzem S , Blumenstein I
Published: January 2025

Background: Background & Aim

Mirikizumab was approved for the treatment of Ulcerative colitis (UC) in May 2023. However, real-world data especially in biological-experienced patients, is scarce. We aimed to determine treatment efficacy and persistence on Mirikizumab in mostly treatment-experienced UC patients.

Methods

All patients, who were treated for UC in the Inflammatory bowel disease (IBD) outpatient clinic of the University Hospital Frankfurt from 07/23-09/24 was retrospectively analyzed. Data on clinical (Simple Clinical Colitis Activity Index (SCCAI)) and biochemical disease activity (fecal calprotectin (FC)) as well and patient history were collected. Patients were followed-up for at least 12 weeks. Observational time-points were Week 0, week 8, week 12 (completion of induction) and after 6 months.

Results

A total of 46 patients were included in this study. Twenty-five patients were Anti-TNF experienced, whereas 21 patients were Anti-TNF naïve. Anti-TNF experienced patients were more likely to have received prior other biologic agents and more likely to have received more than two other biologic agents (p<0.001). The use of concomitant steroids was reduced over time. The spectrum of previous biologic agents was more diverse in the Anti-TNF experienced cohort. Most Anti-TNF naïve patients received Vedolizumab prior to Mirikizumab treatment. We observed a significant increase in patients in clinical remission at week 12 (p<0.05) and at 6 months (p=0.04) in the Anti-TNF experienced group. Furthermore, we observed a significant reduction in fecal calprotectin levels between weeks 0,12 and weeks 20-24 (p=0.018). No relevant side effects were reported, no patients discontinued Mirikizumab due to adverse events

Conclusion

Good efficacy and safety profile for Mirikizumab even in Anti-TNF experienced patients. Better response in Anti-TNF naïve patients indicating an early use of Mirikizumab in the therapeutic sequence.
P0966 Fecal calprotectin in Small Bowel Crohn’s Disease: is it a reliable tool?
Authors: Souto M , Ferreira A I , Gonçalves J , Macedo Silva V , Arieira C , Dias de Castro F , Leite S , Cotter J
Published: January 2025

Background

The correlation between fecal calprotectin (FC) levels and small bowel (SB) inflammation in patients with Crohn’s Disease (CD) remains a subject of debate. This study aims to investigate the relationship between FC levels and SB inflammatory activity in patients diagnosed with SB CD.

Methods

We conducted a retrospective study involving patients with SB CD who underwent small bowel capsule endoscopy (SBCE) and FC testing. Patients with colon inflammation were excluded. Participants were categorized into four groups based on their SB inflammatory status: no inflammation (all three SB tertiles showed Lewis Score (LS) < 135); proximal SB inflammation (first and/or second SB tertiles had LS ≥ 135, with no inflammation in the third SB); distal SB inflammation (third SB tertile had LS ≥ 135, with no inflammation in the proximal SB); pan-SB inflammation (both proximal and distal SB showed inflammation).

Results

A total of 87 patients were included in the study, with a median age of 35 years, 75.9% were female. The distribution of inflammation among the patients was as follows: no inflammation in 21.8%; proximal inflammation in 4.6%; distal inflammation in 33.3%; pan-SB inflammation in 40.4%.

FC levels exhibited an ascending trend of median values along the SB axis: no inflammation 58 µg/g (33-180); proximal SB inflammation 65 µg/g (30-127.7); distal SB inflammation 122 µg/g (42-507); pan-SB inflammation 400 µg/g (205-852). Statistically significant differences in FC levels were observed between pan-SB inflammation vs. proximal inflammation (p = 0.01), and distal inflammation (p = 0.014), with no significant differences in LS.

Additionally, FC showed a positive correlation with LS in the second (r = 0.464, p<0.001) and third tertiles (r = 0.435, p<0.001), but no correlation was noted in the first tertile.

FC demonstrated good predictive capacity for identifying inflammation in the distal SB and pan-SB vs. no inflammation and proximal inflammation, with an area under the curve of 0.790 (p < 0.001) and an optimal cutoff value of 229.5 µg/g.

Conclusion

FC levels correlate positively with the presence of SB lesions in the second and third tertiles of the small bowel. However, it is not a reliable marker for detecting inflammation in the first tertile, highlighting the importance of conducting a SBCE in these patients. These findings contribute to the understanding of FC as a diagnostic tool in managing SB CD.