bluuebunny/crossref_metadata_2025_split huggingface dataset:
P808 Risk of relapse after vedolizumab withdrawal in Inflammatory Bowel Disease for patients in histological remission
Authors: Blad W , Whitley L , Harrow P 
Published: January 2023

Abstract

Background
A key clinical question is whether we should be withdrawing advanced inflammatory bowel disease (IBD) medications after a period of sustained remission. There is data to suggest that risk of relapse on withdrawal of vedolizumab is higher than that of anti-TNF therapy1. Drug costs are still considerable and so withdrawal of medications will also have significant financial benefits.
The aim was to review the outcomes of vedolizumab withdrawal in patients in remission, in particular for those where a clinical decision was made following confirmed histological remission of their IBD

Methods
This was a single-centre retrospective review of patients in the IBD clinic at a tertiary referral centre in London. We analysed all those who had stopped vedolizumab at least six months prior and were in either clinical, biochemical, radiological, endoscopic or histological remission. We assessed for evidence of a flare of disease following withdrawal of vedolizumab and the need of further biological treatment.

Results
38 patients had vedolizumab withdrawal for remission with a median length of treatment of 36 months. 28 (74%) had a flare up of disease requiring medication change with 24 (63%) requiring biologics. 21 restarted vedolizumab and 79% responded to this medication. Importantly, 5 patients are still less than a year since stopping and so still at high risk of relapse.
Of the 21 patients confirmed to be in histological remission, 17 (81%) had a flare of disease requiring further treatment, of which 15 (71%) required biologics. Median time to flare was 7 months with only two patients flaring after a year of cessation. All 15 were started on vedolizumab and 12 (80%) responded to this but one had a subsequent early secondary loss of response. Of those who did not respond to vedolizumab, one required emergency surgery, one responded to ustekinumab and one only has partial response to a third biologic.

Conclusion
Relapse following vedolizumab withdrawal occurs in a significant number of patients even when they have been in remission for a long period of time. It usually occurs quickly within the first year and having confirmed histological remission does not seem influence this risk. Recapture of response is reasonably good and occurs in four fifths of patients. Despite the significant cost savings of stopping vedolizumab, clinicians need to consider the risk to benefit ratio of stopping when relapse is such a common event.
1 Martin, A., Nachury, M., Peyrin-Biroulet, L., et al, GETAID-Vedo-STOP Study Group (2020). Maintenance of Remission Among Patients With Inflammatory Bowel Disease After Vedolizumab Discontinuation: A Multicentre Cohort Study. Journal of Crohn's & colitis, 14(7), 896–903. https://doi.org/10.1093/ecco-jcc/jjaa005
P809 The impact of different treatment strategies in newly diagnosed patients with Crohn’s Disease: a multicentre study
Authors: Revés J , Morão B , Montanaro G , Sciberras N , Bravo A C , Glória L , Ellul P , Torres J 
Published: January 2023

Abstract

Background
The early use of effective therapy may change outcomes in patients with Crohn’s disease (CD). The aim of this study was to compare three different treatment strategies in CD (“top-down”, “accelerated step-up” and “regular step-up” therapy).

Methods
This was a retrospective multicentre study including patients with incident CD between 2009-2021. Patients were categorized into 3 treatment groups: group 1) “top-down”: anti-TNF ± immunomodulator (IM) within the first year of diagnosis with a maximum interval of 6 months between both drugs; group 2) “accelerated step-up”: IM within the first year of diagnosis followed by anti-TNF 6-12 months later, and group 3) “regular step-up”: IM within the first year of diagnosis with or without the need to further escalate to biologic (&gt;12 months after the beginning of IM). The primary outcome was endoscopic healing (EH; SES-CD&lt;3 and no ulcers) at the end of the follow-up; secondary outcomes were CD-related intestinal resection and hospitalization due to CD-flare. Cox regression analysis was performed and Kaplan-Meier curves were computed for each outcome.

Results
156 patients (54% males) were included, with 46% having ileocolonic disease (L3) and 68% an inflammatory phenotype (B1) at diagnosis. Baseline patients’ characteristics in each different treatment strategy are demonstrated in Table 1. Patients were followed for a median of 69 (44-98) months; 12% in group 1 and 19% in group 2 had to switch biologicals (p=0.4); 64% in group 3 escalated to biologicals with a median time since diagnosis of 30 (20-50) months. In group 1, 73% of the patients used concomitant IM. At the end of follow-up, 50% of all patients achieved EH, 20% needed hospitalization and 13% had a CD-related intestinal resection. In a multivariate model adjusted for gender, age at diagnosis, disease location, disease behaviour, perianal disease, and prior surgery, patients in group 3 had a lower probability of achieving EH when compared with patients in group 1 (HR 0.7, 95%CI 0.5-0.96, p=0.02) and group 2 (HR 0.3, 95%CI 0.1-0.8, p=0.01). Kaplan-Meier curves are demonstrated in Figure 1. Using the same model, no differences were found in terms of hospitalization or need for intestinal surgery. Fistulizing disease was a significant predictor for intestinal surgery (HR 2.4, 95%CI 1.5-3.8, p&lt;0.01).

Conclusion
Introduction of biological therapy within the first two years of diagnosis, either in a “top-down” or “accelerated step-up” approach was associated with a higher probability of achieving EH, as compared to the introduction of an immunomodulator followed by a later introduction of biologic. No differences were found for hospitalization or intestinal surgery. Fistulizing disease was a significant predictor for surgical intervention.
P810 Association between Ustekinumab Trough Levels, Serum IL-22 and Oncostatin M Levels with Clinical and Biochemical Outcomes in Patients With Crohn’s Disease
Authors: Bertin L , Gubbiotti A , Buda A , Zingone F , Savarino E V , Barberio B 
Published: January 2023

Abstract

Background
Ustekinumab is an effective treatment for patients with Crohn’s disease (CD). Strategies to monitor response to therapy may improve clinical control of the disease and reduce economical costs. Therefore, we aimed to evaluate if trough levels (TL) of ustekinumab, serum IL22 and oncostatin M levels could be considered early markers of non-response assessing their correlation with clinical and biochemical outcomes in CD.

Methods
We consecutively recruited patients with CD treated with ustekinumab from October 2018 to September 2020. Clinical and biochemical data were collected at baseline, at weeks 12 and 24. TL were dosed at week 12 and week 24, IL22 levels and oncostatin M serum levels were dosed at baseline and at week 12. A primary analysis determined if TL, IL22 levels and Oncostatin M serum levels were associated with clinical response (reduction in Harvey Bradshaw Index score of at least 3 points), clinical remission (Harvey Bradshaw Index score &lt;5) and biochemical remission (negative C-reactive protein (CRP) or fecal calprotectin levels (FC) &lt;250 μg/g). A Shapiro-Wilk test was conducted to test for normality for all variables and a Mann Whitney test was used to evaluate correlation of TL, IL22 and Oncostatin M serum levels with HBI index variation and biochemical remission.

Results
Among 84 patients enrolled, 10 were excluded because they were lost to follow up or had incomplete data. At week 24, 59.4% of patients had a clinical response and 47.9% were in clinical remission. TL dosed at week 12 significantly correlated with clinical response at week 12 (p=0.047) and at week 24 (p=0.019) and with clinical remission at week 12 (p=0.02) and at week 24 (p=0.02). TL at week 12 also correlated with biochemical remission both at week 12 (CRP and FC normalization, p&lt;0.001 and p=0.04, respectively) and at week 24 (CRP and FC normalization, both p=0.01). At week 24, patients with positive FC had higher median trough concentrations of ustekinumab than those with negative FC (p=0.01). Oncostatin M levels at baseline significantly correlated with FC levels at week 12 (p&lt;0.001) and at week 24 (p=0.04), but did not correlate with clinical remission. IL22 levels at baseline were lower in patients in clinical and biochemical remission at week 24, although these trends did not reach statistical significance (p=0.43 and p=0.86).

Conclusion
Ustekinumab was an effective therapy in patients with CD. TL at week 12 were predictive of both clinical and biochemical remission at week 12 and 24. Oncostatin M levels at baseline significantly correlated with FC levels at week 12 and 24.
P812 Fluorescently labelled vedolizumab identified macroscopic and microscopic mucosal drug distribution in patients with inflammatory bowel disease
Authors: Van Der Waaij A , Gabriëls R , Linssen M , Volkmer P , Robinson D , Hermoso M , Karrenbeld A , Festen E , Dijkstra G , Kats-Urgulu G , Nagengast W 
Published: January 2023

Abstract

Background
Biological treatment in inflammatory bowel disease (IBD) patients is currently hampered by high non-response rates. To enhance personalized medicine and predict response to biological therapeutics such as vedolizumab, the working mechanism should be elucidated. We aimed to visualize macroscopic and microscopic vedolizumab distribution and detect drug target cells during quantified fluorescence molecular endoscopy (QFME) to improve understanding of the mechanism of action.

Methods
Vedolizumab-800CW was developed and GMP produced. Forty-three QFME procedures were performed in thirty-seven IBD patients two to four days after intravenous administration of vedolizumab-800CW. Each QFME procedure consisted out of endoscopic assessment of the inflammation status per colonic segment by high-definition white light endoscopy, followed by real-time in vivo assessment of the macro-distribution of fluorescent vedolizumab-800CW signal and quantification by spectroscopy of selected segments. Dose escalation was performed using 0.0 mg, 4.5 mg and 15 mg. Subsequently, two patient cohorts were added that received a dose of 75 mg or 300 mg unlabelled vedolizumab prior to vedolizumab-800CW to assess target saturation. Tissue biopsies were obtained for histopathological assessment, for further ex vivo analysis of the fluorescent signal and for visualization of the microscopic distribution and identification of vedolizumab-800CW target cells by fluorescence microscopy (fig 1).

Results
Both during in vivo QFME and ex vivo analysis a clear dose- and inflammation severity-dependent increase of the fluorescent drug signal was revealed (fig 2). A significant difference was found between the dose groups for non-inflamed (p=0.0004), mild inflamed (p=0.0397) and severe inflamed (p=0.0056) tissue. In addition, the difference in intrinsic fluorescence between the severe inflamed tissue and non-inflamed tissue was significant within the 15 mg (p&lt;0.0001), 75 mg + 15 mg (p=0.0118) and the therapy + 15 mg group (p=0.0005). Fluorescence microscopy revealed clear membrane binding of vedolizumab-800CW to inflammatory cells and migration into the inflamed mucosa. Additional analyses to identify specific target cells are ongoing and immune compositions of regions with high and low vedolizumab signal will be unravelled.

Conclusion
QFME using vedolizumab-800CW elucidated novel detailed macroscopic and microscopic vedolizumab distribution in the inflamed target organ. In addition, its shows the potential of QFME to better understand local drug distribution, target cell identification and target engagement, which could improve understanding of targeted drugs over standard pharmacokinetic and pharmacodynamic analysis.
P823 Biologic Penetration, hospitalization rates and need for major abdominal surgery in inflammatory bowel diseases: a comparative observational study between pediatric and adult patients
Authors: Silva A C V , Tumelero T J , Magro D O , Yamamoto D R , Ribeiro L B M , da Silva G S , Truppel S K , Vieira M C , Kotze P G 
Published: January 2023

Abstract

Background
There is lack of epidemiological data in regard to the accurate situation of Inflammatory Bowel Disease (IBD): Crohn’s disease (CD) and ulcerative colitis (UC) in Brazil. It is known that both diseases' progression is variable and the chronic iinflammation results in structural bowel damage. Comparative data between adult and pediatric patients in the IBD field, regarding different outcomes, is lacking globally. We aimed to analyze the proportion of use of biologicals, need for major abdominal surgery and hospitalizations in CD and UC , between adult and pediatric patients.

Methods
Cross-sectional and multicenter study. Data was collected from all consecutive IBD patients seen as outpatients or admitted to hospital, from 2015 – 2021, in two IBD tertiary centers from a capital from south Brazil. We included all patients with clinical, endoscopic, radiological or histological diagnosis of CD and UC. Patients with unclassified colitis or without available data in medical records for investigating variables of interest were excluded. Patients were classified in two main groups (CD and UC) and in two subgroups each, according to age range: adults and pediatrics. Analyses were made by frequency, proportion, Fisher’s exact test and Chi-squared test, through software IBM SPSS Statistics 28.

Results
Eight hundred and twenty-nine patients were included: 509 with CD (378 adults/131 pediatrics) and 320 with UC (225/95). There was significantly difference between diseases in the proportion of biological use 75.0% in CD and 31.6% in UC (p&lt;0.001), surgeries 49.7%/14,1% (p&lt;0.001) and hospitalizations 58.9%/30.9% (p&lt;0.001), respectively. In CD, there was no difference regarding biological use (80.2% in pediatric group vs. 73.3% in adults; p=0.129), surgeries (46.6% vs. 50.8%; p=0.419) and hospitalizations (64.9% vs. 56.9%; p=0.122). There was significantly difference in biological use (40.0% vs. 28.0%; p=0.048) and hospitalizations (47.4% vs. 24.0%; p&lt; 0.001) in UC and there was no difference regarding surgery necessity between age ranges (17.9% vs. 12.4%; p=0.219).

Conclusion
There was a higher proportion of biological use, surgery and need for hospitalizations in CD as compared to UC. Comparing age ranges, pediatric patients with UC used more biologicals and required more hospitalizations than adults, but there was no difference in the need for abdominal surgery. In CD, there was no significant difference in the three main outcomes, between the age groups.
P825 The course of inflammatory bowel disease in setting of liver transplantation
Authors: Filipec Kanizaj T 
Published: January 2023

Abstract

Background
Liver transplantation (LT) remains the only therapeutic option for patients with primary sclerosing cholangitis (PSC) who develop biliary tract complications or cirrhosis. Around 50-80% of PSC patients have IBD which represent phenotypically unique disease. Patients are prone to negative effects of complications of liver disease and immunosuppression, unpredictable course of both diseases and development of neoplasia. Patients are treated according to standard guidelines related to overall IBD population.

Methods
The study evaluates the IBD course and effects of therapy in PSC transplanted patients. In a period of 2005-October 2022 1453 patients had LT performed at University hospital Merkur, Zagreb, Croatia. 70 (4.8%) of them refers to complications of PSC. 46 (66%) of PSC patients were diagnosed with IBD, majority 43 (93.5%) before LT.

Results
As expected 36 (78.3%) had ulcerative colitis (UC) while 9 (19.6%) Crohns disease. 31 (70%) were males, median age 35 years (IQR 28-47). 35 (76.1%) patients had no IBD activity at LT, whereas 11 (23.9%) had continuously active IBD in follow up. 18 (51.4%) patients with remission at LT developed relapse (median time 536 days, IQR 371-1234) whereas other 17 (48.6%) have stable remission.
Nine (19.6%) patients had malignant disease, 3 (6,5%) cholangiocelular carcinoma in explanted liver, 5 (10,9%) colorectal cancer (CRC) and 1 both tumors.
Before LT 24 (52.2%) patients had no specific IBD treatment, whereas 8 (33.3%) were treated with aminosalicilates (AsA), 5 (10.9%) azathioprine (AzA), 6 (13.1%) glucocorticoids (GK) and 3 (6.5%) biologics.
After LT 23 (50%) are treated with ASA, 12 (26.1%) AzA and 11 (23.9%) biological therapy (36.4% anti-TNF, 27,3% vedolizumab and 36,4% on multiple biologics). AsA as monotherapy is successful in 63.6% of treated patients, AzA in 50% and biologic therapy 27.3%, respectfully. Even though it did not reach statistical significance, more patients with relapse of IBD after LT are treated with AzA than in group of continuously active disease (33.3 vrs 9.1%) while this is opposite for biologic therapy (27.8 vrs 54.5%).
8 (17.4%) patients were treated with total colectomy, 2 before, 3 during and 3 after LT, 6 due to CRC and 2 intractable IBD.
Regrading immunosuppression 42 (91.3%) are treated with tacrolimus, 4 (8.7%) with cyclosporine, 24 (52.2%) with mycophenolate mofetil and 11 (23.9%) prolonged GK.

Conclusion
Management of IBD in the context of PSC and LT setting is a major clinical challenge and specific guidelines are urgently needed. Since the effectiveness of standard therapy is possibly weaker with a high risk of cancer it is necessary to consider an earlier approach to colectomy.
P830 Significant racial and ethnic disparities exist in health-care utilization in inflammatory bowel disease: a systematic review and meta-analysis
Authors: Chhibba T , Tandon P , Natt N , Brar G , Gurpreet M , Geoffrey N 
Published: January 2023

Abstract

Background
The incidence of inflammatory bowel disease (IBD) is rising worldwide though it remains unknown how race and ethnicity mediate health-care utilization. We aimed to better define this relationship in this systematic review and meta-analysis.

Methods
We explored the impact of race or ethnicity on the likelihood of needing an IBD-related surgery, hospitalization, and emergency department (ED) visit. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated with I2 values reporting heterogeneity. Differences in IBD phenotype and treatment between racial and ethnic groups of IBD were reported.

Results
Fifty-eight studies were included. Compared to White patients, Black patients were less likely to undergo a Crohn’s disease (CD) (OR 0.69, 95% CI, 0.50-0.95, I2=68.0%) or ulcerative colitis (OR 0.58, 95% CI, 0.40-0.83, I2=85.0%) surgery, more likely to have an IBD-hospitalization (OR 1.54, 95% CI, 1.06-2.24, I2=77.0%), and more likely to visit the ED (OR 1.74, 95% CI, 1.32-2.30, I2=0%). There were no significant differences in disease behavior or biologic exposure between Black and White patients and between Hispanic and White patients (Table 1). Hispanic patients were less likely to undergo a CD surgery (OR 0.57, 95% CI, 0.48-0.68, I2=0%) but more likely to be hospitalized (OR 1.38, 95% CI, 1.01-1.88, I2=37.0%) compared to White patients. There were no differences in health-care utilization between White and Asian or South Asian patients with IBD.

Conclusion
There remain significant differences in health-care utilization amongst races and ethnicities in IBD. Future research is required to determine factors behind these differences to achieve equitable care for all persons living with IBD.
P832 Cannabis Use in IBD Patients: A Population-Based Study
Authors: Dasu N , John J , Blair B , Khalid Y , Walters R , Chhoun C , Suga H 
Published: January 2023

Abstract

Background
Inflammatory Bowel Disease (IBD) leads to a chronic inflammatory state in the body with significant long-term impact on patient morbidity and mortality. This study investigates the inpatient hospitalization outcomes in patients with IBD with the concurrent utilization of cannabis compared to IBD patients without a concurrent diagnosis to indicate cannabis usage.

Methods
The Nationwide Inpatient Sample (NIS) database encompasses approximately 7 million inpatient hospitalizations annually in the United States. Data were extracted from the National Inpatient Sample (NIS) Database for the years 2015-2019. Patients aged 18 years and above with diagnoses of IBD with concurrent cannabis use were identified. Multivariate regression analysis was used to estimate the odds ratios of in-hospital mortality, the average length of hospital stay (LOS), and hospital charges using STATA 17. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders.

Results
We identified 1,198,839 patients with IBD of which 29,445 were matched to those with cannabis use. The average age was 38.67 years. There was a significant decrease in inpatient mortality (OR 0.28, CI 0.19-0.41, p&lt;0.0001), hospital length of (-0.17 days CI -0.35 -0.01, p&lt;0.041), and total cost of hospitalization (-$11,054.70, CI -13,681.15 - -8427.24, p&lt;0.0001) between patients with IBD with cannabis use when compared to IBD patients without cannabis use.

Conclusion
This study demonstrates a significant decrease in mortality rate, cost of hospitalization, and length of stay in IBD patients with concurrent diagnoses to indicate cannabis usage. This study shows that there are substantial therapeutic effects of cannabis in the management of patients with IBD. Further studies are warranted to investigate the factors that may be driving these differences. Future arms of investigation would be warranted to investigate the effect of cannabis on remission rates, rates of hospitalization, and patient Mayo Endoscopic Scores and Simple Endoscopic Scores for Crohn’s disease.
P833 Cervical cancer risk in newly diagnosed ulcerative colitis: a nationwide population-based study
Authors: Kim H S , Kim H , Kim K 
Published: January 2023

Abstract

Background
The association between ulcerative colitis (UC) and increased risk of cervical cancer in women remains controversial. We investigated cervical cancer risk in South Korean UC patients using the Korean National Health Insurance (NHI) claims data.

Methods
UC definitions included both ICD-10 codes and UC-specific prescriptions. We analyzed incident cases diagnosed between 2006 and 2015. Age-matched women without UC (control group) were randomly selected from the general population (1:3 ratio). Hazard ratios (HRs), adjusted for different covariates, were calculated using multivariate Cox proportional hazard regression. In total, 12,632 and 36,797 women with and without UC, respectively, were enrolled.

Results
Cervical cancer developed in 0.21% (68 person-years) and 0.14% (172 person-years) of UC patients and controls, respectively. The HR (95% CI) of cervical cancer in the UC group, with reference to the control group, was 1.56 (0.97-2.50). HR, stratified by age, was significantly high in elderly UC patients (≥60 years) at 3.65 (1.54–8.66). In UC patients, old age (≥40 years) and low socioeconomic status were associated with increased cervical cancer risk.

Conclusion
Elderly UC patients had a higher incidence of cervical cancer than age-matched controls in Korea, suggesting that elderly patients with newly diagnosed UC should be screened for cervical cancer.