bluuebunny/crossref_metadata_2025_split huggingface dataset:
P850 Symptomatic effectiveness of ozanimod in routine clinical care of ulcerative colitis: an interim analysis of the multicentre, prospective, noninterventional COLIBRI study
Authors: Schubert S , Stein J , Efken P , Helwig U , Schulze J , Hellms T , Jorgensen E , Poehler A M , Scheibner F , Makki M , Zeissig S 
Published: January 2024

Abstract

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

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

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

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

Abstract

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

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

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

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

Abstract

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

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

Results
A total of 79 patients were included (Table 1). Median follow-up was 19 months (2-91); 78.5% were followed &gt;6 months. At 6 months, 80.3% (61/76) and 37.3% (22/59) of the patients were in clinical and endoscopic remission, respectively. 54.3% received combination treatment with immunomodulators (50.6% thiopurines, 3.7% methotrexate). Dose intensification to weekly treatment occurred in 27.8% after median 9 months (4-48 months).
During follow-up 51% received corticosteroids at some point (26% topically-acting oral corticosteroids, 10% oral corticosteroids, 15% both). Of patients who received steroids, 55% (22/40) were able to continue adalimumab therapy. 2.5% of patients were hospitalised for a disease flare. 5.1% had an infection recorded during follow up, none discontinued the treatment. No other major adverse events were recorded.
In 22.8% (18/79) of patients, ADA was stopped due to treatment failure, mean 15 months after starting the drug (4-56 months), (Figure 1). None of these patients underwent colectomy at the time of stopping the drug; in 17/18 a second biological therapy was started (10 tofacitinib, 1 filgotinib, 1 upadacitinib, 2 ustekinumab, 2 vedolizumab, 1 golimumab). TDM was performed using a drug-sensitive ELISA, which is only able to detect antidrug antibodies when drug levels are low or absent. Drug levels at the time of stopping the drug were &lt;5 µg/mL in 22% of patients (in 2 antibodies were detected), 5-8 µg/mL in 11% and &gt;8 µg/mL in 67%.

Conclusion
In a real-world UC cohort, ADA appears to be an effective well tolerated first-line advanced therapy with the vast majority of patients reaching clinical remission and a significant proportion achieving mucosal healing.
Table 1. Cohort characteristics (N 79, frequency and %).

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

Abstract

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

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

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

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

Abstract

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

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

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

Conclusion
This study identifies unique histologic changes in the lymph nodes of patients with UC treated with ozanimod. These changes could be in keeping with the known mechanism of action of ozanimod and suggests that other inflammatory pathways were driving their disease activity in these patients. The significance of the changes, particularly the Castleman-like features, needs to be further investigated.
Table 1: Demographic and clinical data of patients treated with ozanimod and control patients

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

Abstract

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

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

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

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

Abstract

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

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

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

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

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

Abstract

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

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

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

Conclusion
Our panel of IBD specialists rated appropriateness of changing therapy to achieve endoscopic healing in asymptomatic patients with UC and CD in a variety of scenarios. Our findings can be used to help guide clinical decision-making in this population until data from ongoing randomised studies are available (NCT05230173).