bluuebunny/crossref_metadata_2025_split huggingface dataset:
P594 One-year success rates of targeted therapy in Ulcerative Colitis patients revisited
Authors: Creemers R , van Andel E , Wintjens D , van Bodegraven A 
Published: January 2024

Abstract

Background
Multiple new treatment options have been introduced in Ulcerative Colitis (UC) in recent years, leading peers to recommend a treat-to-target treatment approach, including mucosal or even histopathological healing. Patient-reported outcomes, and explicitly those validated on subjective patient-based values, are most commonly neglected in evaluating long-term treatment outcome while being of great importance in defining treatment success.
We re-examined registration and prospective trials with at least one year follow-up to estimate chance of beneficial outcome for patients using the most modern, though surely most expensive, medication. We compared endoscopic improvement and improvement on patient-reported outcomes in the long-term follow-up of new drug therapies in biological naïve patients as a marker for treatment success.

Methods
We assessed long-term endoscopic outcome measures and patient-reported outcomes measures in major registration trials of new biologicals and advanced small molecules in the period 2000-2023 by examination of PubMed. In these trials almost all UC patients had to be 5ASA-, corticosteroid- and/or immune suppressive refractory before inclusion in study.

Results
In figure 1, an overview is shown of long-term endoscopic and PROM improvement endpoints in major registration trials.
When focusing on endoscopic improvement or mucosal healing achieved by biologicals or advanced small-molecules in 5ASA-, corticosteroid- and/or immune suppressive refractory UC patients, most patients did not reach the pre-defined endpoint. In addition, although some registration trials report PROM data, improvement based on PROM’s is not consistently reported.

Conclusion
Reaching endoscopic improvement as definition of treatment success is unsuccessful in more than 60% of patients when accounted for placebo in all modern-era therapies for ulcerative colitis. As a consequence, when endoscopic treat-to-target treatment goals are strictly applied, surgery is warranted in more than 60% of UC patients within one year. Furthermore, lack of reporting of PROMs in registration trials complicate direct comparisons of alternative important endpoints.
P600 Efficacy of different modalities of faecal microbiota transplantation to induce clinical remission in patients with ulcerative colitis: a systematic review and network meta-analysis
Authors: Chapon J , Scanzi J , Pereira B , Sokol H , Buisson A 
Published: January 2024

Abstract

Background
We aimed to compare the efficacy of different modalities of faecal microbiota transplantation (FMT) to induce clinical remission in patients with ulcerative colitis (UC).

Methods
We performed a systematic review and network analysis (random effects model) of randomized controlled trials including at least one arm of FMT in adult patients with active UC. Primary endpoint, i.e. clinical remission (total Mayo score≤ 2 with Mayo endoscopic score≤ 1), was assessed between week 6 and 12. Results are expressed as relative risk with 95% confidence intervals, adjusted for bowel cleansing and pre-FMT antibiotics therapy. Ranking of FMT modalities for clinical remission was calculated as their surface under the cumulative ranking (SUCRA), which represents the percentage of efficacy achieved by an agent compared with an imaginary agent that is always the best without uncertainty. Heterogeneity among studies was evaluated by τ² (global statistical heterogeneity across all comparisons).

Results
Among the 12 selected studies, patients were exclusively bio-naïve in 4 studies (4/12), while between 9 and 32% had prior biologics exposure in the other trials. Risk of bias was low across all domains in 7 studies. Global heterogeneity was negligible (τ² = 0). After adjustment on bowel cleansing and pre-FMT antibiotics, oral capsule (RR=7.1[1.8-33.3]), lower GI FMT (RR=4.5[1.7-12.5] and combination of both (RR=12.5[2.1-100]) were more effective than placebo to induce clinical remission contrary to upper GI FMT (RR=1.1[0.2-7.7]) and autologous FMT (RR = 0.8[0.2-3.8](Table 1).
The combination of lower GI FMT and oral capsule was significantly more effective than upper GI FMT to induce clinical remission (RR=10.7[1.1-104.2]). Combination of lower GI FMT and oral capsule ranked highest for the induction of clinical remission (SUCRA=0.93), followed by oral capsule (SUCRA=0.82) and lower GI FMT (SUCRA=0.72). Autologous FMT ranked lower than placebo (SUCRA=0.12vs0.22). We performed a sensitivity analysis distinguishing single donor FMT and multi-donor FMT (pooled samples from different donors). Combination of lower GI FMT and oral capsule ranked highest for the induction of clinical remission (SUCRA=0.89), followed by single donor lower GI FMT (SUCRA=0.70), multi-donor (pooled samples) lower GI FMT (SUCRA=0.65), multi-donor (pooled samples) oral capsule (SUCRA=0.61), single donor oral capsule (SUCRA=0.60).

Conclusion
In this network meta-analysis, we confirmed the efficacy of FMT to induce clinical remission in patients with UC. The combination of lower GI and oral capsule FMT seems to be the best modality of FMT for patients with UC while upper GI FMT is not suitable. In clinical trials, autologous FMT should be avoided due to a potential detrimental effect.
P603 Comparison of the safety and efficacy of ustekinumab and vedolizumab in patients with Crohn’s disease. - A systematic review and meta-analysis of propensity score matched cohort studies
Authors: Bodini G , Calabrese F , Pasta A , Marabotto E , Furnari M , Demarzo M G , Giannini E G 
Published: January 2024

Abstract

Background
Ustekinumab and vedolizumab represent both valid therapeutic options in patients with Crohn’s Disease following anti-TNF failure. Comparison data regarding safety and efficacy between these drugs are indirect, and reports conflicting results. The aim of the study was to assess the safety and efficacy profile of ustekinumab and vedolizumab in patients with Crohn’s Disease who failed prior anti-TNF treatment, including studies that applied propensity score matching to reduce confounding bias.

Methods
We identified 52 reports that compared ustekinumab and vedolizumab after a propensity score match analysis, of which 14 were assessed for eligibility, and finally 8 retrospective studies were included. The main outcomes considered were clinical steroid-free remission at 14±4, 24±4, and 52±weeks, drug discontinuation rate, adverse events, serious infections, and hospitalisation during the first year of treatment.

Results
A total of 3,185 patients were treated with ustekinumab (n=1,906, 59.8%) or vedolizumab (n=1,279, 40.2%). Steroid-free clinical remission was not significantly different between ustekinumab and vedolizumab at 12±4 weeks (OR 1.14, 95CI 0.76-1.72), at 24±4 weeks (OR 0.92, 95CI 0.56-1.51, p=0.73), and at 52±4 weeks (1.07, 95CI 0.73-1.56, p=0.75). Risk of adverse events was not different between the two drugs (OR 0.65, CI95 0.30-1.41, p=0.28). In patients receiving ustekinumab, the rate of infection (OR:0.52, CI95 0.30-0.91, p=0.02) and the need of hospitalisation at 1-year (OR:0.68, CI95 0.57-0.81, p&lt;0.0001) appeared to be lower.

Conclusion
Ustekinumab and vedolizumab do not significantly differ in inducing and maintaining clinical steroid-free remission, while ustekinumab was associated with a lower risk of serious infections and hospitalisation during the first year of treatment.
P617 Persistent active inflammation may predict non-improvement in bone mass density in patients with Crohn's disease
Authors: Koifman E , Krasnopolsky M , Weisshof R , Waterman M 
Published: January 2024

Abstract

Background
Osteopenia and osteoporosis are associated with Crohn’s disease (CD). Diagnosis is made by dual-energy X-ray absorptiometry scan (DEXA). Pathophysiology of osteoporosis may reflect an interplay between persistent inflammation, steroid usage, as well as risk factors similar to general population. We aimed to identify factors associated with low or deteriorating bone mineral density (BMD) among patients.

Methods
A retrospective case-control study, included patients with CD followed at our IBD clinic from January 2000 to February 2023, with ≥ 2 DEXA scans. The observation started one year before the initial DEXA scan and extended until one year after the second scan. Demographic, clinical and laboratory data as well as medication exposure were collected before and during F/U. Patients were classified into three groups based on change in DEXA results: improved, worsened and no change. Multivariable proportional odds regression model was built to assess independent predictors of change in BMD.

Results
121 patients [60 (49.6%) females, median age 33 years (IQR 23-43), median disease duration 5 years (IQR 0-35), median baseline BMI 22.4 kg/m2 (IQR 12.9-39.3), baseline CRP 1.4 ULN (IQR 0.5-4.5), baseline vitamin D 54.2 nmol/L (IQR 40.9-67.5)], were enrolled and followed for a median of 48 (IQR 29-71) months. At baseline, patients with osteoporosis had a lower BMI (18.5 kg/m2) than patients with normal BMD (26 kg/m2) and osteopenia (22.4 kg/m2), p&lt;0.001. During F/U 63%, 59% and 66% of patients were exposed to high dose CS, anti-TNF and thiopurines respectively.
At the end of F/U,19 (15.7%) patients had deterioration in BMD status while 78 (64.5%) remained unchanged, and in 24 (19.8%) BMD improved. Baseline vitamin D levels (in nmol/L) were higher in patients with improvement in BMD status at the end of the F/U compared to those with maintained or deterioration in BMD (66, 54.2, 41.2; p=0.001, Figure 1). Active smoking was associated with decline in BMD status (p=0.03). No correlation was found between different types of medication exposure and changes in BMD status. In multivariable analysis, elevated CRP was the only independent variable associated with lower odds of improvement in BMD (OR=0.45 (CI 0.2-1.0), p=0.05,Table 1).

Conclusion
Low BMI, low baseline vitamin D levels, and active smoking were found to be risk factors for low BMD status. Elevated CRP was associated with lack of improvement in BMD during the F/U. No correlation was found between different medications and changes in BMD status.
P618 Comparison of vedolizumab and ustekinumab treatment persistence in anti-TNF experienced Crohn's Disease patients
Authors: Eroglu Z , Yilmaz V , Er R E , Soykan I , Toruner M 
Published: January 2024

Abstract

Background
After the approval of vedolizumab and ustekinumab for the treatment of IBD, discussions continue regarding the prioritization of which drug will be used as the first-line treatment. Despite numerous studies in various indications on this matter, there is still no definitive information. It is known that the success of treatments decreases after the use of Anti-TNF in the first step. In this study, we aimed to compare the drug persistence rates of vedolizumab and ustekinumab used as second-line treatments in Crohn's patients with prior experience with Anti-TNF.

Methods
A total of 171 Anti-TNF experienced Crohn's disease patients were included in this study. Age, gender and other demographical info were recorded from patients electronic medial charts. Drug persistence rates were calculated and compared by using Kaplan-Meier Analysis.

Results
Seventy eight patients who received vedolizumab and 93 patients who received ustekinumab were analyzed. In vedolizumab group, 60% of the patients were male where as in ustekinumab group, 57% of the patients were male. Mean age was 39.4 years in vedolizumab group and 41.2 years in ustekinumab group. All patients were anti-TNF experienced. In addition, 70% of the patients in ustekinumab group was vedolizumab experienced. Concomitant azathioprine use was 56% in vedolizumab group where as 34% in ustekinumab group. Drug persistence was significantly higher in ustekinumab group when compared to vedolizumab group (Figure 1). Interestingly, concomitant azathioprine use did not change drug persistence in ustekinumab group however it increased drug persistence in vedolizumab group.

Conclusion
In anti-TNF experienced Crohn's disease patients, ustekinumab treatment persists more longer than vedolizumab treatment. Ustekinumab persistence was independent from concomitant azathiprine use where as concomitant azathioprine use increases vedolizumab persistence.
P639 Tofacitinib induces clinical remission in patients with chronic pouchitis
Authors: de Jong D C , Goetgebuer R , Müskens B , Neefjes-Borst A , Gecse K , Löwenberg M , de Jonge W , Bemelman W , Ponsioen C , D'Haens G , Duijvestein M 
Published: January 2024

Abstract

Background
Up to 10% of ulcerative colitis patients and an ileal-pouch anal anastomosis will develop chronic or antibiotic refractory pouchitis. Several case reports and -series investigated the effect of tofacitinib for refractory pouchitis, but reported conflicting results(1-5). In this study, we aimed to prospectively evaluate the efficacy of tofacitinib in chronic or antibiotic refractory pouchitis using clinical and objective outcome measures.

Methods
We conducted a prospective single centre pilot study in which thirteen patients with chronic or antibiotic refractory pouchitis (Pouchitis Disease Activity Index (PDAI) ≥ 7, ≥2 episodes in the preceding year for which antibiotic therapy was started, or ≥4 weeks symptoms requiring maintenance therapy) were treated with tofacitinib 10mg BID for eight weeks. Clinical, biochemical, endoscopic and histologic disease activity was assessed at baseline and week 8. The primary endpoint was the proportion of patients reaching clinical remission, defined as a PDAI &lt; 7 and a reduction of ≥ 3 points from baseline at week 8. Pouch endoscopy videos were scored by two gastroenterologists and pouch biopsies were assessed by an IBD pathologist, who were blinded to the time points and clinical outcomes. Medians and interquartile ranges were calculated, and Wilcoxon signed rank test was used to analyse changes from baseline.

Results
Thirteen patients (61% male, median age 34 years) were included(table 1). Three patients did not complete eight weeks of treatment due to adverse events (pyelonephritis, primo EBV infection, worsening of pouchitis), two of whom underwent an early termination endoscopy. In total, 31% achieved clinical remission (4/13) and 62% showed clinical response (8/13). Both the total PDAI score (11 (IQR 9 – 12.75) vs 8 (4.5 – 9.75), p = 0.033), and the clinical PDAI subscore (4 (3 – 4) vs 2 (0.25 – 3.75), p = 0.014) decreased significantly from baseline compared to week 8 or early withdrawal, respectively (figure 1). We did not observe a significant change in endoscopic PDAI subscore (4.5 (2 – 5.75) vs 3 (1 – 4.75), p = 0.120) or histologic subscore (3 (2 – 4) vs 2 (1 – 4), p = 0.214). Biochemical parameters did not decrease significantly compared to baseline (faecal calprotectin: 389 mg/kg (38 – 1222) vs 116 mg/kg (31 – 466), p = 0.530 (figure 2) and CRP: 1,2 mg/L (0.75 – 15.2) vs 0.95 mg/L (0.58 – 17.7), p = 0.307, (figure 3)).

Conclusion
In this pilot study, a clinical remission rate of 31% was achieved in patients with chronic pouchitis after eight weeks of treatment with tofacitinib. However, treatment duration of eight weeks is presumably too short to achieve biochemical, endoscopic or histologic response in these refractory patients.
P643 Magnifying Endoscopy with Narrow Band Imaging for Graft Failure and Disease Recurrence in Patients with Crohn’s Disease after Intestinal Transplantation
Authors: Chung C S , Lee T H , Tsai C C , Yu C H , Chen Y 
Published: January 2024

Abstract

Background
Crohn’s disease (CD) is one of the common causes of short bowel syndrome (SBS) and intestinal failure (IF). Intestinal transplantation (IT) is sometimes needed for patients with CD who develop IF after multiple intestinal resections due to CD-related complications, such as uncontrollable bleeding and penetrating diseases. However, there have been limited case reports concerning the endoscopic surveillance of CD patients after IT.

Methods
We retrospectively investigated two patients with CD who underwent IT because of SBS-IF after multiple intestinal resection. We administered post-transplantation immunosuppressants and conducted regular magnifying endoscopy with narrow-band imaging (ME-NBI) via ileostomy chimney for surveillance of grafte rejection. Endoscopic prediction of rejection were based on our previously published "VENCH" score which is composed of five parameters: "V" (villi appearance), "E" (erythema), "N" (capillary network), "C" (crypt widening), and "H" (heterogeneity). Endoscopic biopsy were taken for histologic confirmation of graft rejection severity.

Results
Case 1 was a 60-year-old male patient with CD who received three times of intestinal resection for small bowel stricture and perforation, followed by IT due to SBS-IF. He lived uneventful until seven years thereafter with bloody diarrhea presented. Endoscopic surveillance revealed normal VENCH score of background mucosa but deep longitudinal ulcers which was indicative of recurrence of CD rather than graft rejection. Anti-tumor necrosis factor alpha with adalimumab was prescribed and his diarrhea and graft ulcers improved. Case 2 was a 39-year-old male patient with CD who received extensive intestinal resection due to multiple perforations, followed by IT because of SBS-IF. Endoscopic surveillance revealed normal VENCH score without histologic graft rejection two years thereafter. Both enrolled cases demonstrated favorable outcomes after endoscopic surveillance of intestinal graft with ME-NBI and management accordingly.

Conclusion
The post IT follow-up of CD patients remains challenging. We highlight the usefulness of the ME-NBI using VENCH score for early detection of graft rejection and its value in monitoring CD patients after IT. Additionally, ulcerations without changes in morphology of surrounding villi should take into consideration the disease recurrence of underlying CD. Further research is needed in endoscopic follow-up and molecular genetics to better understand CD after IT.
P652 Transitioning Inflammatory Bowel Disease patients from an intravenous to a subcutaneous infliximab protocol: a single centre experience and patient satisfaction survey
Authors: Mohamed I , Naughton T , Okuwobi K , Walker G , Hanna M 
Published: January 2024

Abstract

Background
Infliximab is used for the treatment of Ulcerative colitis (UC) and Crohn's disease (CD). Subcutenanous (SC) infliximab (CT-P13) received regulatory approval from the European Medicines Agency for Inflammatory Bowel Disease (IBD) in July 2020. Our study aim was to assess the efficacy and safety of SC infliximab in our patient cohort at University Hospital Lewisham as well as gain patient feedback on their experience of subcutaneous infliximab compared to intravenous infliximab.

Methods
We retrospectively analysed the records of all patients receiving infliximab treatment from May 2022 to May 2023 for age, gender, diagnosis, clinical response, faecal calprotectin levels and side-effects. We designed a patient questionnaire for patients who were switched from IV to SC infliximab to assess patient preferences with regards to route of administration, satisfaction with treatment as well as reported side effects.

Results
60 patients (M:F ratio 1:1; average age 36.2y) were receiving infliximab during this time frame. 23 patients were switched to SC infliximab whilst 37 patients remained on IV infliximab. 37/60 (61.7%) had CD, 20/60 (33.3%) UC, and 3/60 (5.0%) IBD unclassified (IBD-U).
Mean faecal calprotectin (FC) levels during treatment were comparable in both groups (Mean FC 117 in IV group; Mean FC 94 in SC group). No patient in either group required hospital admission or gastrointestinal surgery. 1/23 (4.3%) patients switched to an alternate biologic in SC group due to loss of response, whist 3/37 (8.1%) patients in IV group required a switch of biologic therapy over the same time frame.
There were no major side effects reported in either the SC group or IV group. There were 5 minor side-effects recorded in the IV group - 4/37 (10.8%) rash; 1/37 (2.7%) mildly deranged liver function tests. There was 1 minor side effect reported in the SC infliximab group of mild injection site skin reaction 1/23 (4.3%)
18/23 (78.2%) SC infliximab patients completed the patient satisfaction questionnaire. All respondents (18/18, 100%) found the drug more convenient to self-administer than attending the infusion unit for IV infliximab. 1 patient (4.3%) reported mild pain and skin reaction at the injection site. 22/23 (95.7%) of the SC group were satisfied with their treatment and preferred to continue on the SC regimen rather than receive IV infliximab. The one patient who preferred IV infusions reported fear of needles and self-injections as the reason for the IV preference.

Conclusion
Our study showed that SC infliximab was a safe, well tolerated and efficacious treatment compared to IV infliximab. Our patient satisfaction survey showed that a large majority of patients preferred the SC method of administration and were satisfied with their treatment.
P657 Persistence of subcutaneous infliximab after two years of the switch from intravenous infliximab to subcutaneous infliximab in Inflammatory Bowel Disease patients
Authors: Huguet J M , Iborra M , Marti L , Bosca-Watts M M , Ramirez J J , Ruiz L , Sanchis L , Garrido A , Alemany G , Suria C , Paredes J M 
Published: January 2024

Abstract

Background
Biosimilar infliximab (CT-P13) has been available for subcutaneous (SC IFX) administration since march 2021. It has shown to be equivalent to its every-8-week-intravenous formula (IV IFX), however, we do not have long term efficacy and safety data. Our aim was to evaluate medication persistence, efficacy and safety two years after switching from IFX IV to IFX SC

Methods
Multicentre, descriptive, and observational study, with prospective data collection, of Crohn’s Disease (CD) or Ulcerative Colitis (UC) patients who were going to be changed from IV IFX to SC IFX. All patients were on clinical and biological remission for at least 6 months. Clinical activity, analytical data, trough level determinations and adverse events were gathered. Baseline results were compared with those from week 108 after starting CT-P13 SC. Maintenance of the drug after two years and the reason for removal, if so, or of loss of follow-up, were evaluated.

Results
41 patients were included. 24 of whom had intensified doses while 17 were on standard doses (5 mg/kg every 8 weeks). 51% were male; mean age 40.8. 63,4 % (n = 26) had CD. No PCR differences were observed at baseline (IV IFX) [median 0,17 mg/dL] and week 108 [median0,3 mg/dL]. Fecal calprotectin stayed under 200 ug/mg from baseline to 24 months. No changes in clinical indexes were observed. A considerable increase in drug levels was observed after switching to SC IFX at week 108 (6,8 vs 12.3; p &lt; 0,001). 46% of the patients were also on immunosupressor when they switched to IFX SC, and 52% of these had removed it after 2 years of IFX SC. 85% of the patients were still on IFX SC after two years (only one was removed due to loss of response). There were only 3 adverse events, all of which were mild.

Conclusion
Persistence of IFX SC after two years was observed in 85% of the patients. Switching from IV IFX to SC IFX maintains remission in Inflammatory Bowel Disease (IBD) after a 2-year follow-up. Higher drug levels are obtained with the subcutaneous formulation, despite removing the immunosupressor in over 50% of the patients. Switching from IV IFX to SC IFX is safe in IBD.