bluuebunny/crossref_metadata_2025_split huggingface dataset:
P937 A Retropective Analysis of Micronutrient Status in Inflammatory Bowel Disease
Authors: Ruan G , Zhang Y , Yu S , Yang H 
Published: January 2024

Abstract

Background
Researchers are increasingly focusing on the influence of micronutrient levels on the initiation and prognosis of Inflammatory Bowel Disease (IBD). Earlier investigations have highlighted a connection between deficiencies in zinc and selenium and an elevated risk of IBD development and unfavorable outcomes. This study seeks to investigate the existing micronutrient status among Chinese patients with IBD and assess whether deficiencies in trace elements are associated with disease activity, extent of intestinal involvement, and the use of biological treatments.

Methods
This cross-sectional study included patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) who underwent plasma micronutrient testing during outpatient or inpatient visits to the Department of Gastroenterology at Peking Union Medical College Hospital from May 2022 to October 2023. Baseline data, the history of biological agent use, and laboratory inflammation parameters such as hsCRP, ESR, and Alb were extracted from the Electronic Medical Record System. Colonoscopy images were examined to assess the extent of intestinal involvement and endoscopic activity. The distribution of micronutrient deficiency among patients with varying disease statuses was explored using the Pearson chi-square test and Mann-Whitney U-test.

Results
Among the 168 participants with IBD in this study (77 with CD, 91 with UC), a frequent occurrence of deficiencies in copper, selenium, strontium, and zinc was noted. In CD patients in the endoscopic active phase, there was a higher incidence of selenium and zinc deficiencies compared to the remission phase (selenium 0% vs. 11.3%, p=0.17; zinc 4.2% vs. 24.5%, p=0.052). In UC patients during the endoscopic active phase, strontium (14.5% vs. 0%, p=0.053) and zinc (17.7% vs. 3.4%, p=0.094) deficiencies were more likely to occur. CD patients with zinc deficiency and UC patients lacking zinc or selenium showed higher levels of blood hsCRP and ESR but lower levels of serum albumin. UC patients with E3 type involvement were more prone to selenium and strontium deficiencies compared to those with only left colon involvement (selenium 18.5% vs. 2.7%, p=0.025; strontium 14.8% vs. 5.0%, p=0.078).

Conclusion
This study identified a notable prevalence of micronutrient deficiencies in individuals with IBD, particularly during active phases. Specifically, patients with CD in an inflammatory state are inclined to exhibit zinc deficiency. In the case of UC, the absence of selenium, strontium, and zinc signals a higher level of inflammation. UC patients with involvement of the entire colon are more prone to experiencing deficiencies in selenium and strontium. These findings warrant validation through multi-center study and mechanism invetigation.
P943 Real world Effectiveness and safety of tofacitinib in patients with Ulcerative Colitis: 6 months follow-up of the French TOFAST study
Authors: Fumery M , Bouhnik Y , Faure P , Bouzidi A , Brault Y , Peyrin-Boroulet L , Laharie D 
Published: January 2024

Abstract

Background
TOFAST is an observational, prospective, multicenter cohort study aiming to describe the real-life clinical benefit of tofacitinib in moderate-to-severe Ulcerative Colitis (UC).

Methods
We report the results of the interim analysis after 6 months of follow-up, describing patient's characteristics, effectiveness, including change in daily PRO2 scores [RB and stool frequency (SF)] during the first 14 days and the median time to relief, and safety.
Clinical response was defined as a decrease in partial Mayo score (PMS) (≥ 3 points and ≥30%) from inclusion with a concomitant decrease in rectal bleeding (RB) subscore ≥ 1 point (absolute subscore of 0 or 1). Clinical remission was defined as PMS ≤2 with no subscore &gt;1.
Symptomatic relief was reported by patients as the time in days from initiation of tofacitinib to improvement of their symptoms. Safety has been been reported as the % of Adverse Events (AE), serious AE and AE of special interest.

Results
88 patients were included in the safety analysis (one patient was excluded from the effectiveness analysis as he did not meet the eligibility criteria) with a median exposure duration of 11.7 [Q1; Q3: 6.0; 22.1] months. Of these patients, 67 completed a 6-month follow-up visit by 15/07/2023 and were included in the effectiveness analysis.
At inclusion 59.8% of patients were male with a mean (± SD) age of 37.5 ±13.2 years, a median disease duration of 5.9 years [Q1; Q3: 2.7; 13.1]. 46.5% of patients had pancolitis. The mean total Mayo Score was 8.1 ±2.4.
94.3% of patients had previously received at least one anti-TNF agent, 67.8% vedolizumab and 35.6% ustekinumab.
Tofacitinib was initiated at 10 mg b.i.d, in combination with corticosteroids for 35.6% of patients.
At 6 months, 53 (77.9%) patients were still treated with tofacitinib, 58.5% at 10 mg BID dose. Corticosteroids were ongoing in 22.9% of patients.
Clinical response and remission were observed in 64.2% and 61.2% of patients, respectively.
For the 68 (78.2%), patients who reported improvement the median time to relief was 7 days [Q1; Q3: 3.5 ;14.5].
PRO2 scores normalization during the first 14 days is shown in the figure.
84.1% of patients reported at least one adverse event (AE) and 21.6% reported at least one serious AE. Seventeen (19.3%) infections and 3 (3.4%) cases of herpes zoster were observed as well as one non-invasive low-grade urothelial carcinoma. No major cardiovascular or venous thromboembolic event, nor malignancy or death were observed (Table).

Conclusion
In this real-life cohort of patients with refractory UC, tofacitinib induced a clinical response and remission in over 60% of patients, with symptoms relief observed as early as the first two weeks. AEs were consistent with the known tofacitinib safety profile.
P956 Pregnancy outcomes after maternal or paternal exposure in the tofacitinib ulcerative colitis clinical programme
Authors: Mahadevan U , Chaparro M , Segovia Medina M , Kulisek N , Guo X , Wu J , Vranic I , Diehl A , Dubinsky M C 
Published: January 2024

Abstract

Background
Pregnant women with ulcerative colitis (UC) have a higher risk of adverse pregnancy outcomes vs age-matched controls.1 Tofacitinib is an oral Janus kinase inhibitor for the treatment of UC. There are no well-controlled studies on tofacitinib use in pregnant women. It was shown to be teratogenic in rats and rabbits at approximately 73 and 6.3 times, respectively, the maximum recommended human dose of 10 mg twice daily. Tofacitinib affects female fertility, parturition and peri/postnatal development in rats and was secreted into the milk of lactating rats; it had no effects on male fertility or sperm motility/concentration.

Methods
We report pregnancy outcomes in the tofacitinib UC clinical programme: 4 randomised, placebo-controlled Phase (P)2/3 studies (NCT00787202/NCT01465763/NCT01458951/NCT01458574),2,3 an open-label, long-term extension study (NCT01470612)4 and a randomised P3b/4 study (NCT03281304) were analysed.5 Study protocols excluded pregnant women, required females of childbearing potential to use effective contraception and regularly tested for urine β-hCG. Study drug was discontinued in female patients who became pregnant. Pregnancy outcomes after maternal or paternal tofacitinib exposure were identified from Pfizer’s internal safety database up to March 2023 and categorised as healthy newborn, medical termination, foetal death, congenital malformation, spontaneous abortion or lost to follow-up.

Results
There were 40 pregnancies with exposure to tofacitinib: 16 cases of maternal exposure (median age 29.5 [range: 24−41] years), all during the 1st trimester (10 [62.5%] healthy newborns, 2 [12.5%] medical terminations, 2 [12.5%] spontaneous abortions, 2 [12.5%] lost to followup); and 24 cases of paternal exposure (18 [75.0%] healthy newborns, 2 [8.3%] spontaneous abortions, 4 [16.7%] lost to follow-up). There were no cases of foetal death or congenital malformation.

Conclusion
Most known outcomes for maternal and paternal tofacitinib exposure were healthy newborns, similar to previous analyses in other tofacitinib clinical study populations and the general UC population.6,7 Limitations included the low number of reported pregnancies and available follow-up. Tofacitinib should not be used during pregnancy unless necessary.
References:
1. Cornish et al. Gut 2007;56:830−7
2. Sandborn et al. N Engl J Med 2012;367:616−24
3. Sandborn et al. N Engl J Med 2017;376:1723−36
4. Sandborn et al. Aliment Pharmacol Ther 2022;55:464–78
5. Vermeire et al. J Crohns Colitis 2021;15:1130–41
6. Mahadevan et al. Inflamm Bowel Dis 2018;24:2494–500
7. Selinger et al. Frontline Gastroenterol 2021;12:214–24
Study sponsored by Pfizer. Medical writing support provided by S Leneghan, CMC Connect; funded by Pfizer
P961 Achieving treatment targets in Ulcerative Colitis and reasons for failing to do so: Real world experience in a multi-ethnic asian population
Authors: Tan Y B , Ang T L , Ong J P L , Wang L M , Fock K M , Li J W , Kwek A B E , Tan C K 
Published: January 2024

Abstract

Background
In ulcerative colitis (UC), endoscopic remission (ER) is recommended as a long-term treatment target as it predicts favourable outcomes. We performed this study to identify the proportion of patients who achieved treatment targets as set out in the Selecting Therapeutic Targets in Inflammatory Bowel disease (STRIDE II) consensus. Secondly, we aim to identify the reasons for failing to meet treatment targets.

Methods
This is a retrospective analysis of all UC patients who were seen at Changi General Hospital, Singapore from 1 January 2000 to 31 December 2022. Patients were identified from an existing IBD registry. All patients with confirmed diagnosis of UC were included in the analysis. Those with follow up period less than 1 year or no repeat endoscopy were excluded. We collected baseline demographics, disease characteristics, medications, clinical activity scoring, biomarkers, endoscopic findings and histologic reports.
We defined biomarker normalization, ER and histological remission as outlined in the STRIDE II consensus. Next, we compared factors associated with ER. We also assessed possible reasons for failure to achieve ER. SPSS version 26 was used for data analysis.

Results
After excluding 23 patients, a total of 139 patients were analysed with a mean follow-up time of 13.5 years. Figure 1 demonstrates the baseline demographics, disease characteristics, treatment modalities, remission targets and reasons for failure of ER. 96.4% of patients achieved clinical remission with a median time of 8 weeks (IQR: 4). Faecal calprotectin (FC) was not routinely measured at baseline but its use increase significantly after the STRIDE consensus. 53.4% of patients achieved biomarker normalization. ER was achieved in 58.3%. Of the 81 patients who achieved endoscopic remission, 49.4% also achieved histological remission. For patients who had repeat endoscopy within 1 year of diagnosis (35.3%, 49/139), 8.16% had achieved ER with a median time of 34 weeks (IQR: 4).
Lower baseline C-reactive protein (CRP), follow-up FC, partial mayo score (PMS) at follow-up and biomarker normalization were associated with ER (Table 1). Interestingly more extensive disease was also associated with ER.
The main reason for failing to achieve ER was non-compliance to treatment in 58% of the patients. A smaller proportion of patients refused treatment escalation due to absence of symptoms, cost concerns or repeating endoscopy after treatment escalation.

Conclusion
More than half of all patients with UC achieve long term target of ER in our population and baseline and follow-up biomarkers and PMS are associated with ER. Patients’ compliance is the key reason for failing to achieve ER. Thus, patient education should be reinforced to improve treatment outcomes.
P976 Treatment with exclusive enteral nutrition (EEN) impacts the peripheral blood mononuclear cell profile of paediatric patients with Crohn’s disease
Authors: White B , Curle J , Gervais L , Wands D , Nichols B , Hansen R , Russell R , Gerasmidis K , Milling S 
Published: January 2024

Abstract

Background
Background: Despite its established clinical efficacy, the immunological effects of exclusive enteral nutrition (EEN) in Crohn’s disease (CD) are yet to be elucidated. This study investigated the impact of EEN on circulating peripheral blood mononuclear cells (PBMCs) and how any effects observed varied according to clinical response to treatment.

Methods
Methods: Children with active CD received EEN for eight weeks as their sole induction treatment. Blood and faecal samples were collected prior to EEN and upon EEN completion. PBMCs were isolated, stained and analysed using flow cytometry. Differences in PBMCs types were compared during EEN. Faecal calprotectin was measured with ELISA. Absence of gluten immunogenic peptide (GIP) in faeces was used as a proxy marker of EEN compliance.

Results
Results: Nine participants were recruited (Table 1), three of whom initiated azathioprine during their course of EEN. Following treatment with EEN a decrease in the relative number and frequency of circulating effector memory CD8+ T cells re-expressing CD45RA (TEMRA) was observed with a corresponding increase in the frequency of circulating central and effector memory CD8+ T cells (Fig. 1). When we excluded participants that commenced thiopurines during their course of EEN a decrease in the relative number of circulating TEMRA CD8+ T cells persisted and a decrease in naïve CD8+ T cells in the blood was also observed. Participants who demonstrated a decrease in faecal calprotectin 50% following treatment with EEN (n= 5) also demonstrated an increase in the frequency of circulating central memory CD8+ T cells. When focussing on participants (n=7) within our cohort who demonstrated a high-level of compliance (undetected GIP in faeces) during EEN, we again observed a decrease in number of TEMRA CD8+ T cells in blood alongside an increase in the frequency of circulating central and effector memory CD8+ T cells.

Conclusion
Conclusion: We observed significant changes in CD8+ T cell populations in the peripheral blood of children following treatment with EEN. These changes were observed irrespective of background immunomodulator use and persisted in participants which achieved &gt;50% decrease in FC or demonstrated compliance to EEN. Our observed changes in CD8+ T cell populations, particularly the consistent increases in circulating effector and memory CD8+ T cells, are likely a consequence of the actions of EEN in decreasing the diversity and composition of the gut bacteria, therefore reducing the recruitment of effector/memory cells from the blood into the intestine.
P983 Treatment of patients with moderate-to-severe Crohn’s disease with subcutaneous infliximab leads to an endoscopic response across all segments of the colon and terminal ileum: A post hoc analysis of the LIBERTY-CD study
Authors: Sands B E , Dubinsky M C , D’Haens G , Schreiber S , Danese S , Hanauer S B , Kim D H , Lee Y N , Colombel J F 
Published: January 2024

Abstract

Background
Mucosal healing (MH) has been associated with positive long-term clinical and surgical outcomes in patients (pts) with Crohn’s disease (CD).1 Patterns of MH vary by therapeutic agent, with limited efficacy in the terminal ileum.2–4 This post hoc analysis aimed to investigate the pattern of endoscopic MH across intestinal segments in pts who received subcutaneous (SC) infliximab (IFX) maintenance treatment in the Phase 3 LIBERTY-CD study.

Methods
LIBERTY-CD demonstrated superior efficacy of SC CT-P13 120 mg every 2 weeks (Q2W) vs placebo (PBO) after IV IFX induction for clinical remission and endoscopic response at Week (W) 54.5 This post hoc analysis evaluated centrally read and batch analysed Simple Endoscopic Score for Crohn's Disease (SES-CD) values obtained at screening, W22 and W54 for 5 ileocolonic segments (rectum; left, transverse and right colon; and terminal ileum). Pts with missing data or who underwent dose escalation to SC IFX 240 mg Q2W upon loss of response from W22 were imputed as non-responders. Endoscopic complete MH (CMH; defined as SES-CD=0) or partial MH (PMH; defined as ≥50% decrease in the SES-CD from screening) were evaluated for segments that had endoscopic abnormalities at screening (segmental SES-CD ≥1 at screening). Results were analysed descriptively.

Results
Among all randomised pts (N=343; SC CT-P13: n=231, PBO: n=112), the most frequently affected segment at screening was the left colon (187/343; 54.5%), followed by the right colon (185/343; 53.9%), rectum (163/343; 47.5%), terminal ileum (156/343; 45.5%) and transverse colon (134/343; 39.1%). In an analysis of all affected segments, endoscopic CMH rates were higher with SC CT-P13 vs PBO (Figure 1A). Endoscopic CMH rates in the terminal ileum at W54 were 46.7% and 19.6% in the SC CT-P13 and PBO arm, respectively (p=0.0014). PMH rates were also significantly higher in the SC CT-P13 arm across all segments at W22 and W54 (Figure 1B), with rates in the terminal ileum of 64.8% and 33.3% in the SC CT-P13 and PBO arm, respectively (p=0.0003).

Conclusion
SC IFX 120 mg Q2W led to high and consistent endoscopic MH rates across all segments, including the terminal ileum. Early observation of endoscopic MH (at W22) underscores the potency of SC IFX treatment. Further studies are warranted to investigate the association between segmental MH and long-term outcomes.
1Otte ML et al. World J Gastroenterol 2023;29:1157–72.
2Danese S et al. Gastroenterology 2019;157:1007–18.
3Reinisch W et al. J Crohns Colitis 2017;11:425–34.
4Wu Y et al. Therap Adv Gastroenterol 2020;13:1756284820976923.
5Hanauer SB et al. Gastroenterology 2023;164(S6):S220–1.
P985 Efficacy and safety of de-escalation from 50 mg to 25 mg of oral, once-daily, obefazimod for the third and fifth year of open-label maintenance treatment in patients with moderately to severely active ulcerative colitis (UC): An interim analysis
Authors: Dulai P , Sands B E , Danese S , Peyrin-Biroulet L , Dubinsky M , Tilg H , Siegmund B , Sloan S , Ploncard P , Rabbat C , Vermeire S 
Published: January 2024

Abstract

Background
Obefazimod is an investigational, oral, once-daily, small molecule which enhances expression of microRNA-124 and is currently in phase 3 clinical trials for the treatment of patients with ulcerative colitis (UC) [1]. Obefazimod demonstrated efficacy and safety in patients with UC at week-8 in a Phase 2a and Phase 2b, double-blind, placebo-controlled induction trials [2] and their subsequent open-label maintenance (OLM) studies [3].

Methods
Patients with UC who received 50 mg of oral, once-daily, obefazimod for approximately four years in the Phase 2a OLM study and approximately two years in the Phase 2b OLM study, provided they met the eligibility criteria (Mayo Endoscopic subscore = 0 or 1), were given the option to transition to a subsequent open-label maintenance study in which they were administered a daily dose of 25 mg of obefazimod for up to 2 years. This interim analysis, conducted with cut-off date of July 31, 2023, reports the findings of a cohort of patients who completed their week 48 visit.

Results
As of the cut-off date, there were 71 eligible patients, of whom 8 (11%) discontinued prior to week 48 and 63 (89%) completed their 48-week visit. An as observed analysis indicated a disease control rate of 84% (defined as a stable or improved Modified Mayo Score) (Table 1).
The levels of fecal calprotectin were &lt;250 and &lt;150 µg/g for 93% (42/45) and 82% (37/45) of patients with available FCP values, respectively.
In total, 39/76 subjects (51.3%) reported at least one treatment emergent adverse event (TEAE). The most frequent TEAEs (≥ 5%) were COVID-19 (7.9%) and ulcerative colitis (6.6%). No new safety findings were identified over these 48 weeks.

Conclusion
One year after dose de-escalation to a daily regimen of 25 mg of obefazimod, favorable outcomes in disease control were observed among patients with UC who demonstrated endoscopic improvement (ES&lt;1) after 2-4 years of 50 mg od. No new safety signals have emerged for a duration of up to five years of treatment with once-daily obefazimod.
References:
1. Vermeire S, et al. J Crohns Colitis. 2023; doi: 10.1093/ecco-jcc/jjad067; 2. . 2021; 3. Vermeire S, et al. The Lancet Gastroenterology & Hepatology. 2022.
P1005 Dose escalated Infliximab in Inflammatory Bowel Disease - Crohn's Colitis Cure (CCC) Data Insights Program
Authors: Alshiwanna B , Mcnamara J , Wilson W , Pipicella J L , Ghaly S , Gearry R , Begun J , Williams A , Lynch K , Lawrance I , Schultz M , Walker G , Radford-Smith G , Connor S J , Andrews J M 
Published: January 2024

Abstract

Background
Infliximab (IFX) is a monoclonal antibody targeting TNF-α and remains a cornerstone of management of Inflammatory Bowel Disease (IBD). A significant number of people with IBD on standard IFX therapy have persistent disease activity and require dose escalation (DE). In Australia and many other healthcare systems, funding through pharmaceutical benefits schemes is only available for standard dosing. We aim to evaluate the role of DE IFX and patient outcomes in a real-world cohort.

Methods
We performed a cross-sectional observational study using data from Crohn’s Colitis Care, a cloud-based IBD specific electronic medical record used in routine care in Australasia. Data were extracted in November 2023 from 14 private and public care centres. DE was defined as dosing interval &lt;8 weeks and/or dosing &gt;5mg/kg. We examined IBD outcomes prior to and 12 months post DE.

Results
A total of 1725 people received IFX, with DE in 762 (44.2%); 65% had Crohn’s Disease (CD), 33% had ulcerative colitis (UC) and 2% IBD-Unclassified (IBD-U), with a relatively even gender distribution (52.5% male). In the DE cohort, median age was 37 years (IQR 27-49); median age at diagnosis was 23 years (IQR 16-32) and median disease duration 11.6 years (IQR 5.8-17.3). DE and standard dose cohorts did not differ by IBD classification, gender, disease duration, age or age at diagnosis. Median drug level was higher 12-months post DE (8.16μg/ml vs 3.65 μg/ml).
Faecal calprotectin (FCP) remission rate (FCP &lt;250μg/g) was higher 12 months post DE, as was endoscopic remission rate and patient reported outcome remission (Table 1). The rate of systemic corticosteroids was lower 12 months post-DE than pre-DE. In the DE-IFX cohort, measures of healthcare utilisation were lower 12-months post-DE; hospitalisation (56 vs 146; p&lt;0.001), surgical interventions (41 vs 61; p=0.040), endoscopic procedures (210 vs 397, p&lt;0.001) and radiological investigations (243 vs 343; p&lt;0.001).

Conclusion
Within a large Australasian IBD cohort, many individuals on IFX required DE. DE IFX was associated with improved measures of remission as well as a reduction in several measures of healthcare utilisation. These data will be used to undertake formal health economic analysis to determine the price points at which DE is cost-effective; additional data on quality of life and indirect healthcare costs will be important to include for a robust holistic assessment of value in care.