bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1154 Impact of pharmacological therapies for moderate to severe Ulcerative Colitis on health-related quality of life: a systematic review and network meta-analysis
Authors: Katsoula A , Paschos P , Malandris K , Giouleme O , Tsapas A ,   This study was funded by a research grant 2020EOMIFNEp5 from the Hellenic Group for the Study of IBD (EOMIFNE)
Published: January 2025

Abstract

Background
We performed a systematic review and network meta-analysis to evaluate the impact of pharmacological therapies on the health-related quality of life (HRQL) of patients with moderate-to-severe ulcerative colitis (UC) when used as induction therapy.

Methods
We conducted a comprehensive search of electronic databases and grey literature up to September 2024 to identify randomized controlled trials in adults with moderate-to-severe UC comparing advanced therapies. Outcomes included the mean difference in Inflammatory Bowel Disease Questionnaire (IBDQ) score, IBDQ response (defined as a ≥16-point increase from baseline), and IBDQ remission (total IBDQ score ≥170 points). We combined direct and indirect evidence through multivariate random-effects network meta-analyses, and the relative ranking of treatments was assessed using surface under the cumulative ranking (SUCRA) probabilities. Confidence in the estimates was evaluated using the CINeMA (Confidence in Network Meta-Analysis) framework.

Results
Twenty-six randomized, double-blind, placebo-controlled trials with 14 interventions (adalimumab, etrasimod, filgotinib, golimumab, guselkumab, guselkumab/golimumab, infliximab, mirikizumab, risankizumab, tofacitinib, upadacitinib, ustekinumab, vedolizumab and placebo) assessed HRQL using the IBDQ score. Moderate-to-low confidence evidence indicated that all interventions resulted in significantly improved mean IBDQ score compared to placebo (table). Based on SUCRA rankings, upadacitinib and filgotinib emerged as the most effective treatments for IBDQ change, with SUCRA values of 99.5 and 87.0, respectively. For IBDQ response, 18 trials assessing 13 treatments showed that all interventions, except etrasimod and golimumab, achieved clinically meaningful HRQL improvements (≥16-point increase in IBDQ score). Fourteen trials evaluated 11 treatments for IBDQ remission, showing that all therapies except golimumab had significantly higher remission rates than placebo. Upadacitinib, guselkumab and filgotinib had comparable high probability of being the best treatment across IBDQ remission and response outcomes.

Conclusion
Short-term pharmacological therapies consistently improved HRQL in patients with moderate-to-severe UC. Among the treatments evaluated, upadacitinib and filgotinib showed the most substantial benefits in improving IBDQ scores and were highly ranked for both IBDQ response and remission. Head-to-head trials are warranted to validate these comparative benefits and inform optimal treatment strategies.
P1157 Limited Willingness to Switch from Intravenous to Subcutaneous treatment in Pediatric Inflammatory Bowel Disease
Authors: Richter V , Eindor-Abarbanel A , Shalem T , Weiss B , Cohen D L , Shalev-Shamay R , Yerushalmi B , Yerushalmy-Feler A , Topf Olivestone C , Shirin H , Broide E 
Published: January 2025

Abstract

Background
Recent advances in inflammatory bowel disease (IBD) therapies have provided patients with a variety of medications with different routes of administration. We aimed to assess parental preferences regarding medication administration routes and to identify factors influencing these preferences

Methods
This cross-sectional study surveyed parents of children with IBD using a comprehensive questionnaire that focused on treatment experiences, preferences, and attitudes towards switching from intravenous (IV) to subcutaneous (SC) administration. The questionnaire explored various regimens, including oral pills, SC injections at different intervals, and IV infusions

Results
This study included 147 parents of pediatric IBD patients. The median age of the children was 16 years (IQR 14-18), and 64 (43.5%) were female. Most children (94, 63.9%) had CD. The median duration of the disease was 4 years (IQR 2-6). When the parents were asked to indicate their preferred medication route and schedule, the highest score was assigned to SC administration every 8 weeks although this difference was not statistically significant when compared to PO administration daily (2.93 and 2.86 respectively, p=0.68). Both SC every 8 weeks and oral administration were significantly more favored than IV administration every 8 weeks and SC every 2 weeks (p&lt;0.01 for all these pairwise comparisons). There was no statistically significant difference in preference between IV every 8 weeks and SC every 2 weeks (2.16 and 2.05 respectively, p=0.44). [Fig. 1].
Despite new options allowing for SC administration, 67% of parents preferred not to switch from IV, citing concerns about self-injection, desire for nurse presence, and longer intervals between infusions [Fig. 2]. No significant correlation was found between treatment preferences and disease-related factors such as disease type or activity.
Medication doses were most frequently missed via the oral route, indicating challenges with adherence or patient preferences for this administration.

Conclusion
We evaluated the role of parental preferences on the choice of IBD medication administration routes in children, while highlighting the influence of prior treatment experience. The strong resistance to switching from IV to SC treatment, despite the availability of SC options, necessitates a patient-centered approach to clinical decision-making. Clinicians should actively involve parents in shared decision-making processes
P1160 Real-world comparative safety of filgotinib and upadacitinib for ulcerative colitis: a propensity score matching
Authors: Nogami A , Asonuma K , Okabayashi S , Ikenouchi M , Shinzaki S , Fukata M , Kobayashi T 
Published: January 2025

Abstract

Background
We previously reported that upadacitinib (UPA) demonstrated higher effectiveness than filgotinib (FIL) in the treatment of ulcerative colitis (UC) [1]. We aimed to compare safety profiles between FIL and UPA.

Methods
A multicenter, retrospective observational study was conducted in patients with UC over 18 years old who received FIL or UPA from March 2022 to December 2023 at three territory specialist centres in Japan. The adverse events (AEs) observed in each treatment group were reviewed in detail, and the incidence of AEs was compared using 1:1 propensity score matching (PSM), adjusting for gender, age, disease duration, disease extent, severity (partial Mayo score), previous exposure to biologics or tofacitinib, concomitant medications (5-aminosalicylic acid, immunomodulators, corticosteroids), laboratory data (CRP, Hb, Alb), past medical history, and smoking status.

Results
A total of 197 patients were enrolled, including 120 patients treated with FIL (median treatment duration 191 days) and 77 with UPA (median treatment duration 154 days). The incidence of AEs was 25.0% (30/120) in the FIL group and 45.5% (35/77) in the UPA group (p&lt;0.01) (Table). The proportion of AEs that resulted in drug discontinuation was 5.0% (6/120) in the FIL groups and 18.2% (14/77) in the UPA group (p&lt;0.01). Only five patients developed herpes zoster (FIL: 3, UPA: 2). No major adverse cardiovascular events, thrombosis or malignancy due to the medication were observed during the study period.
At the time of AEs identified, 77.1% of the administered UPA doses were 45 mg. In the PSM approach, a cohort of 55 patients in each group was obtained. After PSM (n=55 each) , the incidence of AEs was 14.6% in the FIL group and 43.6% in the UPA group (risk differnce 29.1, 95% confidence interval [CI]: 13.0-45.2, risk ratio 3.00, 95%CI: 1.48-6.09), which was significantly higher in the UPA group than the FIL group.

Conclusion
The higher incidence of AEs observed in this study needs to be taken into account when prescribing UPA although it has relatively high efficacy in UC patients.

References
1.Nogami.A, Asonuma K, Okabayashi S, et al. United European Gastroenterol J. 2024 Nov 13.
P1164 Consumption of red and processed meat may be associated with fatigue and anxiety in patients with IBD
Authors: Hardt H , Wilke E , Herrmann E K , Reindl W , Thomann A 
Published: January 2025

Abstract

Background
Patients with IBD often suffer from extraintestinal symptoms (EIS) such as fatigue, depression and anxiety. The beneficial role of a healthy nutrition is increasingly recognized in IBD as well as mental health, and a Mediterranean diet (MD) is generally recommended for IBD. However, it is not clear which aspects of MD are responsible for the beneficial effects, and dietary assessment can be difficult and time-consuming. We aimed to semi-quantitatively assess 5 simple aspects of dietary habits that are assumed to be either healthy (consumption of fresh/unprocessed products, vegetables, and olive/rapeseed oil) or unhealthy (red/processed meat, “fast food”) and analyze their relationship with EIS.

Methods
Consecutive outpatients (n=215) completed questionnaires regarding fatigue (FACIT-fatigue), depression and anxiety (HADS), and adherence to MD (MEDAS), and provided information about consumption of the abovementioned food choices. We applied a simple scoring system for each item (0-2 for oil, 0-3 for other items), with a possible combined score between 0 and 14 points, higher scores indicating healthier food choices. We calculated Spearman correlations between the 5 items’ scores and EIS scores.

Results
Adherence to MD in our sample was low (median MEDAS 6, range 2-13), median combined 5 items-score was 9 (range 3-13). There was a significant correlation between MEDAS and the 5-item score (ρ .428, p&lt;.001). The majority of patients reported use of predominantly fresh products (77%), and a preference of olive or rapeseed oil over other fat sources (60%). Only 29% consumed at least 1 portion of fresh vegetables per day, and only 2 of 215 patients (&lt;1%) reported to consume at least 3 portions of vegetables daily. Conversely, 47% consumed at least 1 portion of red/processed meat per week, and 15% at least 1 portion daily. Fast food was consumed regularly (1-7 times/week) by 15%. The consumption of red/processed meat correlated positively with fast food consumption (ρ .294, p&lt;.001) and with symptoms of anxiety (ρ .169, p=.013) and fatigue (ρ .164, p=.014)

Conclusion
Our preliminary data show high rates of “unhealthy” dietary habits in an unselected IBD cohort, with surprisingly low vegetable intake. The negative association between consumption of red/processed meat and symptoms of anxiety and fatigue does not survive correction for multiple testing, but is nevertheless intriguing and should be further examined in larger samples. The simple 5-item score correlates with adherence to MD and may be useful as a very quick screening tool, but should optimally be complemented with other nutritional aspects considered relevant for patients with IBD. A respective screening tool is currently under development in our group.
P1166 Factors associated with mesalamine refractory Ulcerative Proctitis requiring advanced medical treatments
Authors: Borkovsky T , Cohen N A , Bannon L , Hirsch A , Ron Y , Thurm T , Maharshak N , Leibovitzh H 
Published: January 2025

Abstract

Background
Ulcerative proctitis, a subtype of ulcerative colitis (UC) affecting the rectum, that in the vast majority of cases is manageable with mesalamine therapy. However, a sub-group of patients become refractory to such treatment, necessitating advanced systemic therapies. We aimed to assess risk factors associated with the need for advanced therapy in proctitis.

Methods
Demographic and clinical data on patients with proctitis were collected retrospectively in a single tertiary center during 2010 to 2024. Proctitis was defined as maximal disease extent of 20cm from the anal verge. Patients who were prescribed immunomodulatory and/or biological therapy were considered refractory proctitis (R-proctitis). Univariate comparative analysis was used to select the features to be included in a multivariate logistic regression analysis to identify the risk factors associated with for R-proctitis. Two-sided p-value &lt; 0.05 was considered significant.

Results
Two hundred and thirty-one patients were included in the analysis of whom 49 (21.2%) were considered R-proctitis. There were no differences between the mesalamine responsive and R-proctitis groups in terms of gender, baseline smoking status, body mass index and follow-up time (Table 1). Mean time to initiation of advanced treatment in the R-proctitis group was 6.2 ± 5.53 years. Compared to the mesalamine responsive group, patients in the R-proctitis group were younger at diagnosis (28.3 ± 14.7 vs. 34.3 ± 15.3, p=0.01), and their baseline colonoscopy showed higher rates of Mayo endoscopic score (MES) 2-3 (86.9% vs. 57.9%, p=0.04) and more extensive disease in cm from anal verge (12.6 ± 5.7 vs. 9.8 ± 5.4, p=0.01). Higher proportion of patients in the R-proctitis were prescribed with topical steroids (50% vs. 17.2%, p=0.001). In the multivariate model, only the use of rectal steroids was significantly associated with progression to R-proctitis (odds ratio [OR] 5.21, 95% confidence interval [CI] 1.56-17.32, p=0.007), while higher baseline MES 2-3 showed a trend (OR 4.31, 95% CI 0.96-19.32, p=0.056).

Conclusion
In this single center retrospective study, the need to use topical steroids was the only significant predictor to progression to R-proctitis necessitating advanced medical treatment. Our results may help stratify patients with ulcerative proctitis who may need closer follow-up and monitoring.
P1168 Real-world evidence comparison of the effectiveness of ustekinumab with anti-TNF or vedolizumab in ulcerative colitis: 2-year maintenance therapy results from the prospective, observational RUN-UC study
Authors: Bokemeyer B , Plachta-Danielzik S , Howaldt S , Mohl W , Efken P , Ehehalt R , Kahl M , Krause T , Trentmann L , Lügering A , Schnoy E , Jochum C , Fajardo Salmon S , Hartmann P , Gilman E , Schreiber S 
Published: January 2025

Abstract

Background
Observational real-world evidence (RWE) studies on the effectiveness of ustekinumab (UST) in ulcerative colitis (UC) are needed in addition to RCTs, which may not represent everyday clinical practice. For this reason, the prospective, controlled, propensity score (PS)-adjusted RUN-UC study was conducted on UC patients starting a new biologic therapy with a follow-up period of up to 3 years. The aim of the present analysis was to evaluate the effectiveness of 2-year maintenance therapy with UST vs. anti-TNF or vedolizumab (VDZ).

Methods
Between 2020-2022, 507 UC patients starting a new therapy with UST or other biologics were enrolled in 34 IBD-experienced centres in Germany. After the exclusion of patients with a stoma, small molecules and missing outcomes, the final sample consisted of 483 patients. Clinical remission (CR) (pMayo ≤ 1 plus a bleeding subscore=0) and steroid-free remission (CR and no systemic use of steroids or oral budesonide) were considered as outcomes. PS adjustment with inverse probability of treatment weighting (IPTW) was implemented to reduce confounders' effect.

Results
A total of 483 UC-patients [153 UST (bio-naïve: 13), 165 anti-TNF (ADA: 30.3%, IFX: 61.8%, GOL: 7.9%) (bio-naïve: 114) and 165 VDZ (bio-naïve: 106)] were included in the analysis. The PS-adjustment reduced systemic differences in the baseline parameters (UST/anti-TNF/VDZ: 43.1/46.1/50.9% males, 23.5/24.2/20.6% EIMs), in particular, the "bio-experienced" characteristic was also equalised, between the groups. Treatment persistence over 24 months showed differences between UST (68.6%), VDZ (73.3%) and anti-TNF (58.8%) (p=0.012), but this was only statistically significant for VDZ vs anti-TNF (p=0.005) but not for UST vs VDZ (p&gt; 0.05) and UST vs anti-TNF (p&gt;0.05) (Figure 1). The PS-weighted 24-month effectiveness (n=367) of UST (mITT analysis) in terms of clinical remission and steroid-free remission (Table 1) differed between the following groups (CR: UST 33.3%, anti-TNF 30.2%, VDZ 48.0%) compared to VDZ (p=0.031), but not compared to anti-TNF (UST vs anti-TNF p&gt;0.05 and anti-TNF vs VDZ p=0.005). A sub-analysis evaluating steroid-free remission in bio-experienced patients after one prior anti-TNF treatment showed no statistical difference. was (UST 41.5%, anti-TNF 20.0% and VDZ 43.8%; p=0.130).

Conclusion
In this prospective RUN-UC study with PS-weighted groups, UST, anti-TNF and VDZ showed a more variable 24-month effectiveness, favouring VDZ over UST and anti-TNF. However, in a subgroup of bio-experienced patients with only one anti-TNF before baseline, steroid-free remission was numerically but not statistically higher with UST and VDZ than with anti-TNF.
P1173 Results of salvage ileal-pouch-anal anastomosis surgery in Ulcerative Colitis patients with restorative proctocolectomy
Authors: Altieri C , Emma E P , Luceri C , Vacca L , Cricchio M , Perna F , Ficari F , Scaringi S 
Published: January 2025

Abstract

Background
Restorative proctocolectomy (PCT) with ileal-pouch-anal anastomosis (IPAA) is the surgical treatment in medically refractory ulcerative colitis (UC).
Short and long-term complications are septic (abscess/fistula), inflammatory (pouchitis/cuffitis) or functional (stenosis/incontinence).
Salvage surgery can be performed in order to avoid permanent end ileostomy, but literature is scarce.
The aim of study is to evaluate the outcomes of IPAA salvage surgery.The primary endpoint was to analyze the percentage of patients who underwent an end ileostomy.The secondary one was to analyze risk factors for complications that lead to an end ileostomy.

Methods
Patients consecutively operated for PCT and IPAA between 1992 and 2020 were retrospectively collected, including demographics, first diagnosis, technical details of the primary IPAA, type of reconstructions and post-operative outcomes.
The group that developed complications was analyzed, describing the outcome of different surgical managements regarding each subgroup of complication. Statistical analysis was performed with a dedicated software.

Results
A total of 225 patients were reported in the observational period:169 were free from complications and 69 (30.6%) underwent pouch salvage surgery; 17 (10.9%) of them had a permanent end ileostomy, while on 52 patients pouch salvage was performed with a good rate of success (89.1%).Among 52.9% of the patients undergoing permanent end ileostomy, an inflammatory complication occurred.
Fistulas (40.5%) were the most frequent and had the best outcome. Pouchitis was present in 9 patients, but 5 of them had a permanent end ileostomy performed.The risk of end ileostomy was higher in male and in patients undergoing numerous surgeries, whilst it is lower in young patients.

Conclusion
IPAA salvage surgery is safe and provides good results with a high rate of success when performed in a referral center.
It has good outcomes concerning septic complications, while it is less effective in treating inflammatory complications.
P1174 Engineering therapeutic Tregs to overexpress GPR15 improves functional fitness for in vivo gut homing
Authors: Müller T M , Liu L J , Wiesinger M , Atreya I , Siegmund B , Atreya R , Berking C , Neurath M F , Voskens C , Zundler S 
Published: January 2025

Abstract

Background
Inflammatory bowel diseases (IBD) like Crohn’s disease and ulcerative colitis, are marked by an imbalance of pro- and anti-inflammatory T cells in the lamina propria of the intestinal tract. Only subgroups of patients respond to current therapeutic approaches designed to restrain pro-inflammatory cells or signalling. Adoptive transfer of autologous ex vivo expanded regulatory T cells (Tregs) has previously been suggested as a promising future therapeutic approach to resolve chronic intestinal inflammation by promoting anti-inflammatory pathways.

Methods
Using a previously established protocol for the ex vivo expansion of Tregs (Investigational Medicinal Product-Tregs; IMP-Tregs), we characterized the migration and homing capabilities as well as the immunosuppressive function of non-expanded and IMP-Tregs using 3D-motility, in vivo gut homing and T cell suppression assays. Furthermore, via electroporation with GPR15 mRNA, IMP-Tregs were engineered to express the gut homing marker GPR15 and tested for their functional fitness in dynamic adhesion, T cell suppression assays as well as in vivo gut homing assays.

Results
Our data show that while the expansion protocol generates highly suppressive Tregs, only a fraction of them is equipped with surface molecules for gut homing. In order to overcome this limitation, we successfully engineered IMP-Tregs to express the gut homing marker GPR15. On a functional level, this led to improved adhesion to the cell adhesion molecules MAdCAM-1 and VCAM-1, which are expressed on the intestinal endothelium, as well as to increased gut homing in a humanized in vivo mouse model without affecting the immunosuppressive character of the engineered IMP-Tregs.

Conclusion
In conclusion, our data indicate superior functional fitness of GPR15-engineered IMP-Tregs for homing to the inflamed gut nominating them a promising further development of autologous Treg transfer therapy for IBD.
P1176 Low serum albumin levels are associated with higher colectomy rates in patients with moderate-to-severe ulcerative colitis on tofacitinib
Authors: Parra PhD R , Fróes R D S B , Magro D O , Ferreira S D C , Mello M K D , Azevedo M F C D , Damiao A O M C , Carlos A D S , Barros L L , Miranda M L Q D , Zabot G P , Vieira A , Sales M P M , Chebli L A , Cassol O S , Lubini M , Alves Jr A J T , Machado M B , Flores C , Teixeira F V , Coy C S R , Zaltman C , Sassaki L Y , Feres O , Chebli J M F 
Published: January 2025

Abstract

Background
This study aimed to evaluate the real-world, long-term effectiveness and safety of tofacitinib in a large cohort of patients with refractory or difficult-to-treat ulcerative colitis (UC).

Methods
A multicentre, retrospective, observational cohort study was conducted, including patients with moderately to severely active UC who received tofacitinib for at least 8 weeks. Outcomes assessed included clinical remission and response, endoscopic response and remission, biochemical response and remission, steroid-free clinical remission, primary and secondary loss of response, drug discontinuation, dose optimisation, the need for colectomy, and adverse events over a follow-up period of up to 30 months.

Results
The study included 127 patients with UC, with a mean age of 40.3 ± 14.2 years; 58.2% were male, 75.6% had pancolitis, and 79.5% had previously failed at least one biological therapy, predominantly anti-TNF agents (70.1%). Clinical remission was achieved by 31.5% of patients at weeks 12–16, 46.5% at 26 ± 4 weeks, and 37.0% at 1 year. Steroid-free clinical remission was observed in 28.6%, 44.8%, and 37.1% of patients at these respective time points. Biochemical remission occurred in 33.6% of patients at 26 ± 4 weeks and 29.3% at 1 year. Endoscopic response and remission within 1 year were reported in 46.0% and 15.3% of patients, respectively. Ten patients (7.9%) required colectomy, and 13 patients (10.2%) were hospitalised, all of whom had previous exposure to biologics. The colectomy rate was significantly higher in patients with baseline serum albumin levels ≤ 3.5 g/dL (21.4% vs. 4.1%, p = 0.013) (Table 1).

Conclusion
This large, long-term real-world study demonstrated that tofacitinib effectively induced clinical remission and endoscopic improvement while preventing colectomy for over 30 months in patients with predominantly biologically refractory UC. The safety profile was favourable. However, baseline hypoalbuminemia was associated with higher colectomy rates, highlighting its prognostic significance.