bluuebunny/crossref_metadata_2025 huggingface dataset:
P837 Improving Vaccination Rates in Patients with Inflammatory Bowel Disease: A Single Centre Audit and Quality Improvement Project
Authors: Leong J , Jiang B , Qiu T Y , Wang L Z , Tan C K , Ong J
Published: January 2024

Background

Patients with inflammatory bowel disease (IBD) are at an increased risk of infections. Vaccine preventable diseases in patients with IBD are associated with high rates of hospitalizations, costs, mortality and longer hospitalizations. Despite societal recommendations, the uptake of vaccinations is still suboptimal. We aimed to conduct an audit of vaccination status in patients with IBD followed by a quality improvement project (QIP) to improve the vaccination rates in the outpatient clinic setting.

Methods

This is a retrospective cohort study in a tertiary hospital in Singapore. Patients with a confirmed diagnosis of IBD aged >18 years’ old who attended outpatient clinics between June to September 2022 were identified, and their influenza (IFV) and pneumococcal (PCV) vaccination status was assessed. A QIP was instituted to increase the rate of IFV and PCV coverage in this ambulatory population. Interventions were directed at both the provider and the patient. All providers were educated on vaccination schedules and a standardized electronic template was implemented for clarity of documentation. Laminated posters of vaccination guidelines were placed in each consultation room. All patients were issued with a personalized vaccination card documenting their vaccination status and serving as a prompt for subsequent consultations. We analysed the rate of IFV and PCV coverage post implementation from November 2022 to June 2023.

Results

70 patients were identified in the pre-intervention cohort. 30 patients were either >65 years old or on immunosuppression, of which 6/30 (20%) received IFV and 11/30 (36.7%) already received PCV. In the post-intervention cohort, we assessed 187 consecutive patient clinic visits which comprised 115 unique patients. Baseline characteristics are detailed in Table 1. 73 patients were either aged > 65 years old or on immunosuppression, 65 patients had no IFV within 1 year, of which 20/65 (30.7%) obtained vaccination coverage for IFV in the post-intervention period (p=0.01). 63 patients were eligible for PCV and 12/63 (19%) received either pneumococcal conjugate vaccine 13 or pneumococcal polysaccharide vaccine 23 during this period (Fig. 1).

Conclusion

A structured QIP with an established protocol engaging patients and guiding providers significantly increased the rate of IFV but not PCV in our cohort. A major hurdle to timely PCV uptake was the erroneous perception of a wider window period by patients and providers given its 5-yearly interval, as compared to IFV. Overall adherence to societal guidelines and uptake of vaccinations is still suboptimal and more work needs to be done to educate providers and patients, increase vaccination uptake and reduce vaccine preventable diseases in patients with IBD.
P838 Determing factors that influence Vedolizumab Response in Inflammatory Bowel Diseases: A Prospective Study
Authors: Knezevic T , Dobrosavljevic A , Odanovic O , Sreckovic S , Kralj Đ , Mitrović M , Svorcan P , Markovic S
Published: January 2024

Background

In recent years, the development of biologic agents, including Vedolizumab, has offered new avenues for the treatment of IBD Understanding the factors that influence the response to Vedolizumab therapy is of paramount importance in optimizing patient care and treatment outcomes. However, for a drug like Vedolizumab, the exact concentration indicating the need for optimization and what influences it are still unknown.

The aim of this research is to evaluate what parameter has influence on good response to Vedolizumab in patients with inflammatory bowel diseases.

Methods

160 patients with Crohn's disease and ulcerative colitis were included in this prospective study, who were treated with Vedolizumab biological therapy from October 2018 to February 2023 at a tertiary center for inflammatory bowel diseases. All patients were followed for a minimum of 14 weeks or until therapy discontinuation. Biochemical parameters (CRP, fecal calprotectin, hemoglobin, ferritin), clinical parameters (MTWS, HBI) were monitored in all patients before and during treatment. Vedolizumab concentration was measured in half of the patients during treatment with this drug. All data were processed using the statistical program SPSS 23.0 (Chicago, IL).

Results

Of the 160 patients, there was almost an equal distribution between male and female (males, 160/86 (53.7%)), with an average age of 51.5 years (± 16.51 SD). After one year of therapy, a statistically significant reduction in inflammation parameters was observed (FCP- p=0.007, Z= -2.694; CRP- p=0.008, Z= -2.646), as well as a statistically significant clinical response to therapy by reducing the disease activity index (p < 0.000, Z= -4.818). Using logistic regression duration of disease nor disease localization are predictive parameters for response to therapy (p = 0.330, Exp B 1.190) In a group of 80 patients, Vedolizumab concentration was measured in a cross-sectional analysis. Our cohort of patients had a median Vedolizumab concentration of 20.73 µg/ml. Patients who achieved remission had statistically similar Vedolizumab concentrations compared to patients with active endoscopic disease (Vedolizumab concentration UC 25.6541 vs 28.8152; p = 0.614; CD 20.0232 vs 18.3346 µg/ml; p = 0.729). Patients on Vedolizumab who had previously received anti-TNF therapy had a lower mean drug concentration compared to bio-naive patients (16.05 ug/ml / 20.34 ug/ml).

Conclusion

Previous anti-TNF therapy may have an impact on drug concentration and response to therapy, but it is necessary to determine other parameters that can also independently influence drug concentration
P842 Assessment of body composition parameters in patients with inflammatory bowel disease treated with biological therapy
Authors: Spirić J , Topličanin A , Vuksanović S , Nikolić A , Jovičić I , Đuranović S , Popović D , Đelić M , Dragašević S , Sokić Milutinović A
Published: January 2024

Background

There is growing evidence of the role of biological therapy (BT) in improving body composition parameters (BCP) in inflammatory bowel disease (IBD) patients. Since myopenia and high adiposity affect prognosis and could lead to treatment failure, there is the need for expanding the assessment of BCP in clinical practice beyond traditional measures like body mass index (BMI).

Methods

A cross-sectional study included 151 IBD patients treated with BT (80 males, 83 Crohn`s disease, 68 ulcerative colitis, mean age 37). Bioelectrical Impedance Analysis (InBody170) was done to estimate: body weight, BMI, skeletal muscle mass (SMM), body fat mass (BFM), percent body fat (PBF), fat free mass (FFM). Dividing SMM, FFM and BFM by height squared, we calculated the skeletal muscle mass index (SMI), fat-free mass index (FFMI) and fat mass index (FMI).

Results

In relation to BMI, 84 (55.6%) patients had healthy weight, 41 (27.2%) were overweight, 13 (8.6%) were obese and 13 (8.6%) were classified as underweight. Clinical remission was present in 139 (92.6%) patients. The average values of the measured BCP are as follows: body weight 71.7kg (41.4-123.7); body height 174.6±10.9cm; BMI 23.7kg/m2 (15.1-36.9); PBF 24.6% (5-48); SMI 9.7kg/m2 (6.3-13.5); FFMI 17.5kg/m2 (12.0-23.5); FMI 5.7kg/m2 (1.0-17.3). Muscle mass parameters were significantly higher in the group of patients treated with BT longer than 3 months (SMI p=0.01, FFMI p=0.02), while in the group of patients treated longer than 1 year we observed, apart from muscle mass parameters, a significant increase in adiposity parameters (FMI p=0.02, PBF p=0.06). [WU1] Patients who previously had the need for change of BT type had significantly higher values of FMI (p=0.04). Patients with extraintestinal manifestations (EIMs), compared to the group without EIMs, had statistically significantly lower values of body weight (p=0.02), SMI (p=0.01), and FFMI (p= 0.01). There was no statistically significant difference in BCP by IBD subtype, presence of clinical remission, BT type and protocol, previous operations, corticosteroids, mesalazines and azathioprine use.

Conclusion

The duration of treatment with BT can significantly affect muscle mass and adiposity parameters, leading to improved muscle mass parameters after 3 months of therapy, while an increase in adiposity markers is observed after 12 months of BT. Our findings suggest a potential association between EIMs and muscle mass alterations, as well as a relationship between the need for a change in BT type and higher adiposity parameters.
P853 Factors associated with intestinal tissue levels of anti-TNF in pediatric patients with Crohn's Disease
Authors: Dotlacil V , Coufal S , Lerchova T , Zarubova K , Kucerova B , Tlaskalova-Hogenova H , Kverka M , Bronsky J , Skaba R , Hradsky O , Rygl M
Published: January 2024

Background

Despite advancements, understanding the tissue pharmacokinetics of Anti-tumour necrosis factor alpha monoclonal antibodies (aTNF) and addressing cases of primary non-response, secondary loss of response, and unexplained treatment failures in some patients pose ongoing challenges.

The aim of this study was to investigate factors associated with intestinal tissue levels of aTNF, anti-drug antibodies and cytokines in paediatric patients with Crohn's Disease (CD).

Methods

A prospective study of paediatric CD patients treated with aTNF, who underwent ileocecal resection or colonoscopy between June 2020 and January 2023 was performed. Tissue drug levels of aTNF, anti-drug antibodies and pro-inflammatory cytokines ((TNF alpha (TNF-α), interleukin-17 (IL-17), interleukin-1 beta (IL-1β), interferon gamma (IFN-γ)) were analysed in tissue culture supernatant using ELISA.

Logistic regression estimated odds ratios (OR) adjusted for potential confounding from disease localization, way of sampling, presence of inflammation, and type of anti TNF (aOR).

Results

Twenty-seven CD patients (18 females, 66.7%) with a median disease duration of 50 (Interquartile range [IQR] 23 – 69) months were analysed. Fourteen (52%) received adalimumab (ADA), thirteen (48%) received infliximab (IFX), with a median aTNF therapy duration of 17 (IQR 4.5 – 41.5) months. Tissue aTNF detection was 100% in ADA-treated and 81.8% in IFX-treated patients.

A positive association between intestinal inflammation and the level of free aTNF in tissue was observed (aOR=3.03, 95% CI=0.82-5.29). The ratio of aTNF level in tissue to serum was higher in the inflamed tissue (aOR=0.21, 95% CI=0.039-0.38).

Despite an adequate level of aTNF in the serum, no measurable level was detected in the tissue in 13 patients.

When comparing anti-drug antibodies levels in serum and tissue, we found a notable discrepancy, with 19 patients having undetectable serum levels, while tissue levels were measurable.

We found higher tissue IL-17 levels in patients who had been treated with aTNF therapy for a longer period (aOR=0.15, 95% CI=0.031-0.274), independent of disease duration and patient age.

An association was found between the level of IFN-γ and the duration of follow-up, as well as with the duration of aTNF administration. However, it was not possible to determine which of these associations is responsible for this relationship.

Conclusion

Our study highlights significantly elevated free drug levels in inflammatory tissue compared to non-inflammatory tissue. Our findings also align with recent insights linking aTNF failure to upregulation of mucosal IL17, providing a possible molecular rationale for improved treatment response with treatment targeting the IL-23 receptor after aTNF treatment failure.
P880 The real-world use of five-aminosalicylate (5ASA) treatment for Ulcerative Colitis in Australia and New Zealand: Crohn’s Colitis Cure (CCC) data insight’s program
Authors: Pipicella J L , McNamara J , Wilson W , Lynch K , Walker G , Begun J , Lawrance I , Ghaly S , Radford-Smith G , Williams A J , Gearry R , Schultz M , Brett L , Andrews J M , Connor S J
Published: January 2024

Background

Five-aminosalicylates (5ASAs) promote & maintain remission in people with ulcerative colitis (UC) and are administered orally or rectally, with combination therapy (oral + rectal) more effective than oral monotherapy, especially when treating flares1. 5ASAs may be perceived as out-dated and thus neglected. With increasing UC incidence & prevalence in emerging nations, understanding real-world 5ASA use and value is vital.

Methods

Crohn’s Colitis Care is a cloud-based electronic medical record used in Australasia. Data feed into a de-identified clinical quality registry (CQR), which was interrogated in September 2023. People with UC under active care (encounter within 14 months) were included.

Results

Of the 2,522 eligible people, 78.4% resided in Australia & 21.6% in New Zealand (NZ). The median age was 41 years (IQR 31-56), with an even gender distribution (50.3% female). Median disease duration was 9 years (IQR 4.4-16.7). Median duration of follow up was 25.9 months (IQR 13.0-41.4). Overall, 39.2% (n=989) had no documentation of 5ASA therapy (42.0% in Australia, 28.9% in NZ; Table 1). In those with documented 5ASA therapy (60.8%, n=1,534), the average 5ASA treatment duration was 9 years (IQR 4.4-16.7) and women were more likely to receive rectal administration than men (p<0.05). In those who ceased 5-ASA therapy, 782 (44.8%) had a reason documented, with the most common being medication rationalisation and/or deep remission (40.0%) (Figure 1), usually due to up-titration to a more advanced therapy.

A total of 608 (39.6%) were recorded as already receiving additional IBD therapy at CQR entry (immunomodulators [IMs]/biologics/small molecules). Of those receiving 5ASAs alone at CQR entry (n=926), 5ASAs were subsequently judged to have failed in 37.8% (n=350). 5ASA failure was defined as the need for additional IBD therapies (99.1%, n=230 for IMs/biologics/small molecules and n=117 for steroids, total n=347); hospitalisation (n=3, 0.9%) or IBD surgery (n=0).

Conclusion

Despite not working for everyone, the long duration of 5ASA therapy indicates they are well tolerated & perceived as beneficial by consumers. There was greater 5ASA utilisation in NZ, possibly due to restricted advanced therapy access. Gender-specific trends in 5ASA administration were identified, raising the question as to why this should be so, given this is not obviously explained by disease phenotype. Further analysis is needed to tease out how such trends interact with other therapeutic access, choices and outcomes.

1 - Probert C et a. Combined oral and rectal mesalazine for the treatment of mild-to-moderately active ulcerative colitis: rapid symptom resolution and improvements in quality of life. J Crohns Colitis. doi:10.1016/j.crohns.2013.08.007
P910 Salivary calprotectin as a prognostic biomarker in Early Onset Inflammatory Bowel Disease: a cohort study
Authors: Liguori S , Musella G , Coppola N , Adamo D , Cantile T , Spagnuolo G , Del Giudice C , Miele E , Staiano A , Mignogna M D , Leuci S
Published: January 2024

Background

Inflammatory Bowel Disease (IBD), including Ulcerative Colitis (UC) and Crohn’s Disease (CD) affects children in 25% of cases. In Early Onset IBD (EOIBD) oral involvement is common and oral manifestations (OM) are frequently the first presenting sign of disease.

This study compared salivary calprotectin (SCp) between EOIBD and healthy controls (HC), differentiating patients based on their history of OM. Furthermore, this report correlated salivary and faecal calprotectin (FCp) in EOIBD and assessed the prognostic accuracy of SCp in predicting disease relapses.

Methods

A cohort study was conducted; 9 HC and 27 EOIBD (18 UC and 9 CD) were recruited at the University of Naples Federico II. EOIBD were divided in two subgroups based on the history of OM.

A sample of stimulated whole saliva was collected by each participant by spitting. The samples were then processed by ELISA for determining SCp.

For each patient clinical disease activity was measured through Paediatric Ulcerative Colitis Activity Index (PUCAI) and Paediatric Crohn’s Disease Activity Index (PCDAI), at baseline and during follow-up (4/8/12 weeks).

At baseline, patients provided a stool specimen for FCp determination.

SCp levels were compared between groups. In EOIBD SCp was correlated to clinical data and to FCp.

Results

At baseline all the patients were in treatment with immunosuppressive drugs; 19 were in clinical remission (PUCAI/PCDAI <10) and 8 had mild disease (PUCAI/PCDAI<35). 13 EOIBD had an history of OM: 12 suffered from aphthous-like manifestations while 3 reported granulomatous lesions; 10 experienced oral involvement before IBD diagnosis. OM were more prevalent in CD than in UC and were associated to ileocolic, perianal and upper gastrointestinal tract involvement.

EOIBD with OM reported significantly higher SCp than EOIBD without OM and HC: 155,79±60,08 pg/mL in EOBD with OM vs 82,95±51,58 pg/mL in EOIBD without OM (P<0,01**) and 98,21±39,67 pg/mL in HC (P=0,21).

Despite the systemic therapy and the clinical remission, in 7 EOIBD with OM oral lesions persisted. These patients had higher SCp compared to those who experienced OM remission (P<0,05*).

In EOIBD with OM higher SCp was associated to higher FCp (P<0,05*) while in EOIBD without OM this correlation was not described.

No correlation was found between SCp values and PUCAI/PCDAI at baseline.

EOIBD with OM who reported higher SCp were found to have increased risk of relapse (P<0,05*) while no association was reported in EOIBD without OM.

Conclusion

In EOIBD with OM SCp is significantly higher, mirrors intestinal inflammation and predicts relapses. Our results suggest the use of SCp as a prognostic biomarker in EOIBD with OM although more studies are needed.
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

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

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<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<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

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

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

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 >17 years at disease presentation had almost three times the odds for response at 12 months, compared to patients who were < 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 >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

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 < 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 < 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

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 >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 <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

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)>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<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.
P950 Advancing Precision Nutritional Assessment in Inflammatory Bowel Disease (IBD): Adding Fecal Calprotectin in the Malnutrition Inflammation Risk Tool (MIRT) score
Authors: Dhoble P , Desai D , Abraham P , Gupta T , Dharap V , Kutar M
Published: January 2024

Background

Most of the nutritional assessment tools assess only nutrition. The Malnutrition Inflammation Risk Tool (MIRT) incorporates both malnutrition and inflammation (CRP).1 However, CRP is a less sensitive biomarker than fecal calprotectin for the assessment of inflammation. Adding fecal calprotectin (FC) in the MIRT score may improve the assessment of malnutrition risk. FC level cutoff of < 250 mg/kg in adults correlate with endoscopic remission with good sensitivity and specificity.2 Fecal calprotectin level greater than 800 µg/g is predictive of a need for rescue therapy.3

Aim

To study if adding fecal calprotectin to CRP by improves the yield of MIRT score

Methods

This is a single center, prospective, cohort study including consecutive patients with IBD (Ulcerative colitis {UC} and Crohn’s disease {CD}). Malnutrition was defined as per European society for clinical nutrition and metabolism (ESPEN guidelines): BMI <18.5 kg/m2 or unintentional weight loss >10% (indefinite time). MIRT score was calculated with BMI, weight loss and CRP and MIRT-FC by adding FC to CRP with as shown in the table below:

Results

During 2019 to 2021, 200 patients included, median age 39 years (IQR 28-53) (105 UC, 93 CD and 2 IBD-U), 60 (30%) patients had malnutrition (32 UC, 26 CD and 2 IBD-U and 27 (45%) malnourished IBD patients had MIRT score > 3. CRP values were normal in 30 (50%). Adding fecal calprotectin to MIRT score malnourished IBD patients, 46 (76%) malnourished IBD patients had MIRT score > 3 (P=0.005). This modification (MIRT FC) increased the yield of existing MIRT score by 31%.

Conclusion

MIRT-FC score improved the yield of MIRT score. Prospective studies are required to validate this further.

References:

1. Jansen I, Prager M, Valentini L, Büning C. Inflammation-driven malnutrition: a new screening tool predicts outcome in Crohn’s disease. British Journal of Nutrition. Cambridge University Press; 2016;116(6):1061–7.

2. D'Haens G, Ferrante M, Vermeire S, et al. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis 2012; 18:2218-2224.

3. Sasidharan S, Sasson AN, Shannon KM, Ananthakrishnan AN. Fecal Calprotectin Is a Predictor of Need for Rescue Therapy in Hospitalized Severe Colitis. Inflamm Bowel Dis. 2022;28(12):1833-1837.
P964 Vedolizumab trough concentrations during subcutaneous treatment in patients with inflammatory bowel diseases
Authors: Heijnen M , Straatmijer T , Maljaars J , van Schaik F , Visschedijk M , Tack G , Jansen J , Löwenberg M , van der Meulen A , Šebek L , Vasbinder E , Duijvestein M
Published: January 2024

Background

An exposure-response relationship has been described for intravenous (IV) vedolizumab (VDZ), but little is known about through levels and real life outcomes of subcutaneous (SC) VDZ treatment. We aimed to study the effect of SC VDZ in a prospective real life cohort and assessed what clinical variables are associated with vedolizumab trough concentrations.

Methods

IBD patients initiating VDZ SC treatment were included in our nationwide, prospective Initiative on Crohn and Colitis (ICC) registry. Adult IBD patients were included if a known trough level during IV and SC therapy was available. Two different assays were used for trough levels measurements : i.e. an enzyme linked immunosorbent assay (ELISA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The primary outcome measure was the mean VDZ trough concentration during maintenance treatment (after at least four SC injections). In addition, associations between VDZ serum trough concentrations and corticosteroid-free clinical remission were assessed. A Receiver Operating Characteristic (ROC) analysis was performed to determine the concentration threshold that was associated with corticosteroid free clinical remission after 4 SC VDZ injections (i.e. defined as a Harvey Bradshaw Index (HBI) score ≤ 4 for CD and a Short Clinical Colitis Activity Index (SCCAI) score ≤ 2 for UC).

Results

In total, 24 with Crohn’s disease (CD) and 32 with ulcerative colitis (UC) patients were included. Twelve patients started SC VDZ after a maximum of three VDZ infusions and 44 patients switched to VDZ SC after at least four VDZ infusions. The mean VDZ trough concentration was 34.4 µg/mL (SD 12.9) after 13 (IQR 11-20) weeks of SC treatment. The mean VDZ trough concentration increased from 20.5 µg/mL to 35.2 µg/mL (P < 0.001) in patients who switched from IV to SC VDZ. Biochemical remission (defined as a C-reactive protein (CRP) ≤ 5 µg/mL with a faecal calprotectin (FC) ≤ 250 µg/g) prior to the switch, VDZ measurements using LC-MS/MS and higher VDZ levels during IV therapy were associated with higher VDZ serum levels during SC therapy. Active smoking and prior use of >1 biologic and/or tofacitinib were associated with lower VDZ levels during SC therapy (table 1). A VDZ trough concentration of ≥ 34.5 µg/mL during SC maintenance therapy predicted corticosteroid free clinical remission with a sensitivity, specificity, positive predictive value and negative predictive value of 60%, 75%, 86% and 43%, respectively.

Conclusion

VDZ serum concentrations were significantly higher during SC therapy versus IV treatment. A VDZ trough concentrations ≥ 34.5 µg/mL was associated with corticosteroid free remission.