bluuebunny/crossref_metadata_2025_split huggingface dataset:
P913 Intestinal Ultrasound in paediatric Crohn’s disease reduces the need for subsequent ileocolonoscopy
Authors: Dorn-Rasmussen M , Boysen T , Jakobsen C , Wewer V 
Published: January 2024

Abstract

Background
Approximately 20% of patients with Crohn's disease (CD) are diagnosed during childhood (pCD). At diagnosis, the vast majority (87%) of patients with pCD demonstrate severe disease activity.(1) Severe disease activity necessitates intensive treatment followed by frequent blood tests, faecal calprotectin tests, and endoscopic procedures. Ileocolonoscopy is burdensome for the patient, as bowel preparation and general anaesthesia are needed, and furthermore, the procedure is costly. In recent European guidelines for pCD management, Intestinal Ultrasound (IUS) is recommended for clinical follow-up. Our objective was to investigate the extent to which patients with pCD underwent subsequent endoscopy after having IUS performed during their follow-up regimen.

Methods
We conducted a retrospective descriptive cohort study, encompassing all patients with pCD at a referral center (Department of Paediatric and Adolescence Medicine, Copenhagen University Hospital, Amager and Hvidovre) who had undergone a minimum of one ultrasound examination over a 2.5-year period (May 1, 2021, to November 1, 2023).

Results
A total of 29 patients with pCD were enrolled in the study. Demographic data can be found in Table 1. The median follow-up since time of diagnosis was 40 months (interquartile range (IQR) 30-57). Time to the first IUS examination after diagnosis was median 28 months (IQR 13-49). The indications for IUS were as follows: Clinical suspicion of disease activity and/or elevated faecal calprotectin levels (66% of cases), evaluation of disease activity after initiating biologic therapy (10%), assessment of disease activity status (14%), suspicion of treatment failure (7%) and other indications (3%). Following the IUS procedure, 10% of patients subsequently underwent ileocolonoscopy, which was performed within 11, 14, or 53 days after IUS. Among the remaining 90% of patients, 14% underwent ileocolonoscopy 8-16 months after the IUS procedure, while 76% never had a repeat ileocolonoscopy performed after a median follow-up of 342 days (IQR 247-441) after IUS.

Conclusion
In 90% of patients with pCD IUS can be used to evaluate disease activity without the necessity for an ileocolonscopy in the subsequent 12 moths of follow up.
References:
(1) Wewer MD, Langholz E, Munkholm P, Bendtsen F, Benedict Seidelin J, Burisch J. Disease Activity Patterns of Inflammatory Bowel Disease-A Danish Nationwide Cohort Study 1995-2018. J Crohns Colitis. 2023 Apr 3;17(3):329-337. doi: 10.1093/ecco-jcc/jjac140. PMID: 36124895.
P918 Can we rely on HLA to predict resistance to biological therapy in Inflammatory Bowel Disease patients?
Authors: Domingues Â , Carvalho A , Martinho A , Araújo R , Silva A , Ministro P 
Published: January 2024

Abstract

Background
Monoclonal antibodies revolutionized IBD therapy, although some patients do not respond or progressively loose response due to antidrug antibodies. Immunogenicity seems to be related with HLA haplotypes, namely HLA-DQA1*05 allele associated with an increased risk of immunogenicity to anti-TNF therapy in CD. There are no data regarding the association between HLA-DQA1*05 positivity in UC patients and other biological drugs.

Objectives
We aim to determine HLA-DQA1*05 prevalence in IBD patients and evaluate its association with loss of response to biological therapy. As a secondary endpoint we aim to evaluate the effect of HLA-DQA1*05 genotype in a composite outcome that encompasses clinical, biochemical, and endoscopic remission at week 54.

Methods
Single center prospective cohort study, including consecutive adult bio-naïve IBD patients followed at IBD consultation, that initiated biological therapy. Data was collected regarding demographic, disease characterization and disease activity at baseline. All patients were screened for HLA-DQA1*05. Pharmacokinetic data was collected, and biological therapy was adjusted based on standardized protocols. Patients were classified as primary non-responders or as secondary non-responders. Response assessment was carried out at week 54 with a composite outcome that encompasses clinical, biochemical, and endoscopic remission. Statistical analysis: Chi-square test; Student’s t-test; Mann Whitney test; Kaplan-Meier survival analysis.

Results
We included 100 patients (67 CD, 33 UC), of whom 33 primary non-responders, 12 secondary non-responders and 55 achieved w54 of treatment. Patients started anti-TNF (72 patients, 51 Infliximab and 21 Adalimumab), Vedolizumab (18 patients) or Ustekinumab (10 patients), and 26 were on combined therapy. 43 (43%) patients were HLA-DQA1*05 positive. Kaplan-Meier survival analysis revealed no statistically significant differences in therapy persistence between HLA groups in all patients. However, a Kaplan-Meier survival sub analysis revealed patients under Vedolizumab had significant lower therapy persistence if HLA-DQA1*05 positive (p&lt;0.001). UC´s patients revealed tendency to lower therapy persistence if HLA-DQA1*05 positive, although not statistically significant (p=0.051). HLA-DQA1*05 negative patients under Vedolizumab achieved our composite outcome (p&lt;0,001) and patients under anti-TNF revealed a higher response to the composite outcome but without statistical significance.

Conclusion
HLA-DQA1*05 genotyping demonstrated no impact in therapy persistence, except in the subgroup of patients treated with Vedolizumab. HLA-DQA1*05 negative patients had a higher response to the composite outcome, but with statistical significance only in Vedolizumab subgroup.
P923 Haematological abnormalities during treatment with Janus kinase inhibitors in patients with Ulcerative Colitis: a post hoc analysis
Authors: Loveikyte R , Voorneveld P W , Dijkstra G , van der Meulen - de Jong A E 
Published: January 2024

Abstract

Background
Janus kinase inhibitors (JAKi) are used for Ulcerative Colitis treatment and could lead to haematological abnormalities, such as anaemia. In this post hoc analysis, we evaluated whether treatment with tofacitinib or filgotinib is associated with anaemia and other haematological laboratory abnormalities.

Methods
Data from randomized clinical trials [OCATVE 1 (NCT01465763), OCTAVE 2 (NCT01458951), OCTAVE Sustain (NCT01458574), and summary-level data from SELECTION (NCT02914522)] evaluating the efficacy of filgotinib and tofacitinib were used in this post hoc analysis. Adult patients with moderate-to-severe Ulcerative Colitis received induction therapy with filgotinib, tofacitinib, or placebo. After induction, patients in remission were re-randomized to receive either filgotinib 100 mg QD, filgotinib 200 mg QD, tofacitinib 5 mg BID, tofacitinib 10 mg BID, or placebo. We evaluated and compared the proportions of patients with anaemia, leukopenia, neutropenia, lymphopenia, and thrombocytopenia at baseline, after induction therapy (i.e., 8–10 weeks), and after 52–58 weeks of maintenance therapy in these treatment groups.

Results
At least a third of patients across all treatment groups had anaemia at baseline, the proportion of those who recovered from anaemia after induction did not differ (Table 1): 29.9% in the tofacitinib 10 mg group, 25.6% in the filgotinib 200 mg, and 30.7% in the filgotinib 100 mg group (P = 0.571). The proportion of patients who developed anaemia after the induction phase also did not differ: 16.7% in the tofacitinib 10 mg group, 17.3% in the filgotinib 200 mg, and 12.1% in the filgotinib 100 mg group (P = 0.880), as presented in Table 1. In contrast, 3.1–5.6% of patients in the tofacitinib groups vs. 7.1–14.5% in the filgotinib groups developed anaemia after 52–58 weeks of treatment (P = 0.036); however, the difference was not statistically significant after correction for multiple testing. Other haematological laboratory abnormalities, except lymphopenia, either did not occur or occurred infrequently across all treatment groups. Data regarding lymphopenia was available only from the OCTAVE trials; after 52 weeks of maintenance therapy, approximately 22% of patients in the tofacitinib groups had lymphopenia compared with 3.8% in the placebo group (P = 0.008).

Conclusion
Heterogeneous data limited this post hoc analysis. Haematological laboratory abnormalities, except for anaemia and lymphopenia, were infrequent. Therapy with JAKi was not associated with an increased occurrence of anaemia. However, since lymphopenia occurred more frequently in patients under treatment with tofacitinib, close monitoring is advisable to manage the risk of infection in these patients.
P926 Improved standards of colonoscopy for Inflammatory Bowel Disease through implementation of key performance measures - A quality improvement initiative
Authors: Vaitiekunas L , Subhaharan D , Kakkadasam Ramaswamy P , Edwards J , John S 
Published: January 2024

Abstract

Background
Improving the quality of colonoscopy in inflammatory bowel disease is expected to improve clinical outcomes for patients. The European Society of Gastrointestinal Endoscopy (ESGE) recently published key performance measures for IBD colonoscopy assessment. This study aimed to assess the impact of implementing key performance measures and assess for sustainable improvement through a multimodal education intervention.

Methods
A baseline retrospective analysis was performed in patients with established IBD between June and August of 2022 at a tertiary hospital. The key performance measures included 1) pre-procedure metrics including indication, consent, and safety checklist (target of 100%) and 2) bowel preparation score, photo-documentation, disease activity scores, adequate biopsies, use of high-definition endoscopy and chromoendoscopy. There were six proceduralists involved and data was collected from electronic medical records including endoscopy and histopathology results. The ESGE performance measures were used to set minimum standards and we have adopted overall standards for our unit based on the ECCO and SCENIC consensus guidelines. Over 12 months, proceduralists and endoscopy nursing staff were engaged with educational interventions including didactic teaching for one hour and diagrammatic reminders in the endoscopy suites of the ESGE key performance measures. A post-implementation analysis was conducted at 1 year from baseline, from August to November of 2023.

Results
Baseline standards showed suboptimal performance in the use of disease activity scores and chromoendoscopy. Educational interventions were implemented and after 12 months, a repeat analysis of 50 consecutive patients showed significant improvement in all performance measures (see Table 1).

Conclusion
Quality metrics are important and underrecognised components in colonoscopy for IBD patients and form an integral part of improving patient care. Our study demonstrated that the implementation of the ESGE key performance measures is effective in improving the quality of colonoscopy assessment in IBD patients, identifying areas requiring further development and increasing the dysplasia detection rate. Acknowledging quality attrition over time, we recognise that regular teaching and education are required in addressing the challenge of sustainable long-term improvement.
P929 Relation between Crohn’s disease phenotype and response to ustekinumab in Stockholm – the STOCUSTE study
Authors: Bello F , Muhsen S , Sabhan H , Borin A , Johansson F , Höög C , Forsberg O , Wennerström C , Söderman C , Lördal M , Almer S 
Published: January 2024

Abstract

Background
Ustekinumab, an anti-interleukin-12/23 antibody, has successfully been introduced in the treatment of Crohn’s disease, mainly in patients failing tumor necrosis factor alpha inhibitors (aTNF). As Crohn’s presents with different phenotypes, we hypothesized that response to ustekinumab treatment may differ depending on disease characteristics.

Methods
This retrospective study included 322 unselected patients diagnosed with Crohn’s disease and treated with ustekinumab in Stockholm, Sweden, between 2016 and 2021. The primary outcomes were clinical remission (physician global assessment, PGA =0), response (PGA decrease of ≥1, from baseline), and drug persistence at 3 and 12 months. Subsequently, we calculated odds ratio for drug persistence, clinical response, and clinical remission in relation to several phenotypic disease characteristics.

Results
Disease location was 15% Ileal (L1), 43% colonic (L2), 41% Ileocolonic (L3), and 7% isolated upper GI (L4), in addition, 22% had fistulizing disease. Some patients had a combination of L4 and L1, L2, or L3. The intention-to-treat response rate was 43% at 3 months, and 42% at 12 months. No difference in outcome was observed in relation to disease location or presence of fistulizing disease. Patients who were &gt;17 years at disease presentation had almost three times the odds for response at 12 months, compared to patients who were &lt; 17 years at diagnosis (Table 1). Almost three times lower clinical remission rates were observed in patients exposed to aTNF agents and vedolizumab prior to ustekinumab, compared to patients exposed to aTNF only (OR 0.38, CI 0.18 – 0.79, p-value 0.01). Higher remission rates were related to age &gt;17 years at disease presentation, however this lost statistical significance in the adjusted logistic regression model. Previously operated patients had double the odds to still be on ustekinumab at 12 months compared to un-operated patients (Table 2).

Conclusion
In this Stockholm-based Crohn’s disease cohort, the distribution of disease location was well balanced. Considering isolated ileal inflammation and fistulizing disease as markers for disease severity, a substantial part of the cohort had a high disease burden. Nevertheless, there was no statistically significant difference in any of the outcomes in relation to ileal location or fistulizing disease. These results indicate that ustekinumab is a viable treatment option for all location-related phenotypic expressions, as well as fistulizing character. However, patients who previously failed two biologics, and could be considered difficult-to-treat patients, had a worse outcome on ustekinumab compared to patients who were not treatment refractory before.
P933 Closing the internal opening with a rectal advancement flap increases the effectiveness of mesenchymal stem cell (MSC) injection in the treatment of complex Crohn's disease anal fistulas
Authors: Fathallah N , O'Neill C , Haouari M A , Barré A , Roland D , Alam A , Kassouri L , Safa Far E , Spindler L , de Parades V 
Published: January 2024

Abstract

Background
The injection of MSCs into complex anoperineal fistulas of Crohn's disease gives a combined clinical and radiological remission of between 35 and 50% at 12 months. In our department, surgical closure is now done by rectal advancement flap (and no longer with simple stitches) in order to minimize the passage of stools and contamination of the fistula tract.
The aim of this study was to compare the remission rate and the quality of life between patients treated with MSC injection using simple stitches versus a rectal flap to close the internal opening.

Methods
This single-center prospective study included all our consecutive patients who had a MSC injection. The first patients of the series who had closure of the internal opening(s) with stitches (2020- 2022) were compared with those who had a flap (2022-2023).
Complete clinical remission was defined by complete closure of the external opening(s) without pain or discharge, and complete radiological remission by a Magnifi-CD score equal to 0 (Hindryckx P, et al. Gastroenterology 2019). Quality of Life was assessed by the Crohn's Anal Fistula Quality of Life scale (CAF-QoL) (Adegbola SO, et al. Gut 2021).

Results
We included 68 patients (50% women, mean age: 38 ± 13.8 years). The first 42 had stitches and the following 20 had an advancement flap (6 patients had no procedure due to an anal stenosis). The median follow-up was 12 months [6-24].
The overall complete clinical remission was 66.7% at M12: 51.1% [35.5-66.8] in the "stitches" group versus 87.5% [69.7-100.0] in the "flap" group (p = 0.005) (Figure). The difference was noticed early from M1.
The mean overall Magnifi-CD MRI score decreased from 15.5 ± 4.7 to 6.5 ± 7.1 at M12 (p &lt; 0.001) with no difference between the 2 groups. However, more patients in the flap group had a Magnifi-CD score of 0: 62.5% versus 38.2%.
The CAF-QoL quality of life score improved from 51.3 ± 24.7 to 21.2 ± 20.8 at M12 (p &lt; 0.001) with no significant difference between the 2 groups.
The duration of the procedure was longer on average by 19 ± 7 minutes in the "flap" group.
There was no difference in the anal incontinence score between the 2 groups.
In logistic regression, the advancement flap was significantly associated with complete clinical remission (p = 0.007, HR (95% CI): 2.3 [1.3-4.3]).

Conclusion
Closing the internal opening with a rectal advancement flap improves the effectiveness of MSC injections with a complete clinical and radiological remission rate of 87.5% and 62.5% respectively, without consequences on anal continence.
P941 Observational study of tofacitinib in ulcerative colitis in Sweden (ODEN) – Interim analysis of clinical and biomarker data
Authors: Nyberg L , Söderling J , Olén O , Strid H , Jäghult S , Halfvarson J , Hedin C , Jónsdóttir S , Hjortswang H , Cappelleri J , Henrohn D , Seddighzadeh M , Marsal J , Grip O 
Published: January 2024

Abstract

Background
Tofacitinib is a Janus kinase (JAK) inhibitor for the treatment of moderate to severe ulcerative colitis (UC). ODEN is an ongoing Swedish multicentre prospective observational study regarding effectiveness of tofacitinib in UC. In this interim analysis, we aimed to assess the clinical outcomes during the first 16 weeks.

Methods
Patients with active UC were enrolled 2020-2023 when starting tofacitinib as per clinical indication. Inclusion criteria were fecal (F) calprotectin &gt;250 mg/kg or Mayo endoscopic score ≥2. Data were collected using an electronic case report form linked to the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG). Data concerning inflammatory markers, endoscopic activity, partial (p) Mayo, extra intestinal manifestations, health-related quality of life measures, corticosteroid use, and colectomy rates were collected regardless of tofacitinib discontinuation. Information collected at week 8 and 16 is presented here. Intention-to-treat (ITT) analysis was applied and tofacitinib discontinuation was considered as treatment failure (i.e., no tofacitinib-induced clinical or laboratory response or remission). McNemar’s test was used for proportion differences.

Results
The proportion of patients who previously had failed at least one biologic was 95% and at least two biologics, 62%. At inclusion, median p-Mayo was 5 and 39% of patients were on corticosteroids (Table 1a). Patients’ survival on drug is shown in Figure 1a. At week 8 and 16, 42% and 43%, respectively, achieved corticosteroid free clinical remission, Figure 1b. A 50% reduction in F-calprotectin was seen in 54% and 49% at week 8 and 16, respectively. The endpoint of Mayo endoscopic score 0 and/or F-calprotectin &lt;100 mg/kg was achieved by 30% and 38% at week 8 and 16, respectively. Arthralgia frequency decreased significantly from baseline from 29% at inclusion to 13% and 11% at week 8 and 16 respectively. Three patients underwent colectomy the first 16 weeks (Table 1b).

Conclusion
After 16 weeks of treatment with tofacitinib, a substantial proportion of previously treatment refractory UC patients were in clinical and endoscopic corticosteroid-free remission, and a distinct improvement in F-calprotectin levels was observed. In addition, a significant reduction in arthralgia was noted.
P944 Ustekinumab in refractory Ulcerative Colitis: single-center, real-world experience
Authors: Herrera De Guise C M , Mayorga Ayala L F , Robles Alonso V , Serra Ruiz X , Céspedes Martínez E , Lastiri Gonzalez E , Pérez Martínez Z , Oller Jimenez E , Casellas F , Borruel Sainz N 
Published: January 2024

Abstract

Background
Ustekinumab, an anti-interleukin 12/23 agent, was approved by the European Medicines Agency in 2019 as a treatment for moderate-to-severe ulcerative colitis (UC). Limited real-world data is available regarding the utilization of ustekinumab in UC, particularly medication persistence and escalation, which are indicators of medication performance in real-world settings. Our aim was to describe our experience with ustekinumab in refractory UC patients.

Methods
This was an observational single-center study on UC patients who received at least one intravenous dose of ustekinumab 16 weeks before data analysis due to active UC (Simple clinical colitis activity index (SCCAI)&gt;5). Data regarding disease activity prior to and post-induction were analyzed. Patients were followed up until the last ustekinumab administration. Clinical response to therapy was assessed at 16, 24,52 weeks, and the end of follow-up. Response was defined as SCCAI&lt;4, and remission as SCCAI≤2. Dose adjustment or IV maintenance was considered part of the treatment regimen. Patients who discontinued ustekinumab due to lack of therapeutic effect or worsening of UC were considered failures. When available, colonoscopy data was analyzed.

Results
Forty-seven patients who received ustekinumab for refractory UC were included. Thirty-eight percent were female, and 34% were former smokers. Median age was 46 [37.5-61.5]; 62% had extensive disease, and 15% had perianal disease. Ninety-three percent received at least one biologic before ustekinumab, and 24% had received a JAK inhibitor. Thirty-eight patients required dose escalation, and 11 were on maintenance IV. Clinical response at week 16 was achieved in 74% and remission in 46%. At 24 and 52 weeks, 65% and 61% were in remission, respectively. At the end of follow-up, 59% of patients had endoscopic remission (Endoscopic Mayo score ≤ 1). Sixty percent continued treatment during a mean follow-up of 12 months [6-21]. No variable was associated with risk of discontinuation. No serious adverse events were reported. Discontinuation of treatment was due to treatment failure in all cases.

Conclusion
Ustekinumab was effective for induction and maintenance in our cohort of UC patients, although a significant proportion required dose escalation. Drug persistence was higher than 50% during the follow-up. The safety profile of ustekinumab was similar to that in controlled studies and other real-world studies.