bluuebunny/crossref_metadata_2025_split huggingface dataset:
P613 Comparative objective effectiveness of vedolizumab and ustekinumab in a real-life cohort of active Crohn’s disease patients failure to TNF inhibitors
Authors: Onali S , Pugliese D , Caprioli F A , Orlando A , Biancone L , Nardone O M , Imperatore N , Fiorino G , Cappello M , Viola A , Principi M B , Bezzio C , Aratari A , Carparelli S , Mazzuoli S , Manguso F , Grossi L , Bodini G , Ribaldone D , Mocci G , Minerba L , Favale A , Grova M , Scucchi L , Segato S , Fries W , Castiglione F , Armuzzi A , Fantini M C 
Published: January 2022

Abstract

Background
The use of ustekinumab (UST) and vedolizumab (VDZ) as second line therapy in Crohn’s disease (CD) patients failing tumour necrosis factor alpha inhibitors is still debated. The aim of the study was to compare in a large multicentre observational retrospective cohort, the effectiveness of UST and VDZ as second line therapy as assessed by clinical and objective outcomes including endoscopy and gastro intestinal (GI)-imaging.

Methods
Clinical response, remission and steroid-free remission at week 26 and 52 were evaluated in a retrospective cohort of CD patients previously experienced TNF-alpha inhibitors (primary or secondary failure, and intolerant). Objective response and remission were evaluated by one or more techniques including ileocolonoscopy, magnetic resonance (MR)/computer tomography (CT) enteroclysis and small bowel ultrasound (US) performed within 3 months before the beginning of the treatment and after one year of therapy. Inverse propensity of treatment weighting (IPTW) and propensity score matching (PMS) methods were used for statistical analysis.

Results
470 CD patients (239 UST and 231 VDZ) were included in the study. At week 26 clinical response, clinical remission and steroid free remission were similar between the two groups (Figure 1) At week 52, clinical remission and steroid-free remission rates were significantly higher in VDZ-treated patients (clinical remission: UST 42.5% vs VDZ 55.5%, p=0.01; steroid-free clinical remission UST 40.6% vs VDZ 51.1%, p=0.038; Figure 1). 302 patients (135 UST and 167 VDZ) had objective evaluation of disease activity at baseline and week 52. At week 52 objective response and remission rates were similar between the groups. (Figure 2). Clinical response at week 26 predicted steroid-free remission at week 52 in both UST- and VDZ-treated patients. Safety profiles were similar between the two groups.

Conclusion
One-year treatment with VDZ was associated with higher rate of clinical remission as compared to UST, but no difference was observed between the two groups when objective outcomes were investigated
P615 Improving IBD monitoring by understanding preanalytical faecal calprotectin variability
Authors: Schröder O , Farrag K , Böcher A , Helmschrodt A , Aksan A , Ehehalt R , Stein J M 
Published: January 2022

Abstract

Background
Currently, faecal calprotectin (fCal) is considered the best available biomarker for both diagnosing and monitoring IBD. However, little is known about the stability of this protein in stool: The few studies available are contradictory. Our aim was to investigate the pre-analytical and biological variability of fCal in order to provide tools for its interpretation in the clinical setting.

Methods
Samples from 36 patients with IBD were collected to verify the preanalytical stability of fCal. Aliquots of homogenised stool were stored at room temperature and 37°C and fCal concentration measured for 7 consecutive days. In addition, fCal stability was assessed at each respective temperature in assay-specific extraction buffer.

Results
Baseline fCal concentration in stool samples varied from 14 to 2210µg/g. In aliquots or raw stool samples kept at room temperature, mean change from baseline on days 1, 4 and 7 was -30,95%, -43,66%, and -58,68%, respectively. This decline was irrespective of fCal concentration at baseline, but significantly reduced by using an assay-specific extraction buffer (Fig.1).

Figure 1.

Conclusion
fCal is not stable at room temperature. Patients with IBD and their carers may be falsely reassured by low calprotectin values. Our results indicate that for preanalytical fCal handling, samples should only be stored at room temperature in the short term (up to 24 h). While refrigeration may be suitable for up to 48 h, the use of special extraction fluids improves fCal stability for a longer period. The sending of stool samples by post should therefore be avoided unless extraction buffer is used.
P624 Long-term effectiveness of anti-TNF therapy in pediatric-onset inflammatory bowel diseases: a population-based study
Authors: Fumery M , Savoye G , Ley D , Dupont C , Bertrand V , Spyckerelle C , Guillon N , Desreumaux P , Gower-Rousseau C , Sarter H , Turck D , Leroyer A 
Published: January 2022

Abstract

Background
Anti-TNFs antibodies are the first biologic treatment option in inflammatory bowel disease (IBD). The long-term effectiveness of this strategy at the population level is poorly known, particularly in pediatric-onset IBD.

Methods
All patients diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) before the age of 17 between 1988 and 2011 in a population-based registry were followed retrospectively until 2013. Among patients treated with anti-TNFs, the cumulative probabilities of anti-TNF failure defined by primary failure, loss of response or intolerance were evaluated. Factors associated with anti-TNF failure were investigated by a Cox model.

Results
Among a total of 1007 patients with CD (median disease duration, 3.2 years IQR (1.2–7.6) and median follow-up 8.8 years (IQR, 4.6–14.2)) and 337 patients with UC (median disease duration, 2.5 years IQR [1.1–4.5] and median follow-up 7.2 years (IQR, 3.8–13.0)), respectively 481 (48%) and 81 (24%) were treated with anti-TNFs. Median age at anti-TNF initiation was 17.4 years (IQR, 15.1–20.9). Median duration of anti-TNF therapy was 20.4 months (IQR, 6.0–59.9). In CD, the probability of failure of 1st line anti-TNF therapy at
1, 3 and 5 years was respectively 29.3%, 47.0% and 54.6% for infliximab (n = 397) and 22.6%, 37.7% and 48.0% for adalimumab (n = 83). In UC, the probability of failure of 1st line anti-TNF therapy at 1, 3 and 5 years was respectively 37.3%, 49.0% and 61.0% for infliximab (n = 71) and 12.5% for these 3 timepoints for adalimumab (n = 10). In CD, probabilities of primary failure, loss of response and intolerance at 5 years were 10.4%, 36.7% and 6.8% (n = 480), respectively; in UC, these same probabilities were 7.5%, 39.2% and 11.3% (n = 81), respectively. Female sex (Hazard Ratio (HR) 1.43, 95% CI 1.09–1.87; p = 0.010) and intestinal resection prior anti-TNF initiation (HR 1.73, 95% CI 1.21–2.47, p = 0.003) were associated with anti-TNF failure in multivariate analysis.

Conclusion
In a population-based study of pediatric-onset IBD, approximately half of anti-TNFs users discontinue use within 5 years. Loss of response account for around two-thirds of failure, both for CD and UC.
P625 Predictors of pancreatitis among patients with inflammatory bowel disease (IBD) treated with vedolizumab (VDZ): Observation from a large global safety database
Authors: Wernicke J , Verstak T , Zhang T , Spalding W , Lee L , Cheng Y , Ademi A 
Published: January 2022

Abstract

Background
Patients (pts) with IBD are at increased risk of pancreatitis. Here, we report a post-marketing safety analysis to identify predictors of pancreatitis utilising data captured during treatment with VDZ in a large Global Safety Database (GSD).

Methods
Takeda’s GSD was queried for case reports (CRs) of adverse events (AEs) following VDZ treatment, from licensure (20 May, 2014) through 31 March, 2021. Unsolicited and solicited CRs of pancreatitis were coded using the Medical Dictionary for Regulatory Activities (version 24.0) high-level term “Acute and chronic pancreatitis”. A comparator was created using data from 600 CRs of random, non-pancreatitis AEs; cases meeting the regulatory definition of serious criteria were compared with serious CRs (SAEs) of pancreatitis. Unadjusted comparisons were performed using t-tests for continuous data and Chi-square tests, Fisher’s exact tests for categorical data. Logistic regression analysis was performed to adjust for covariates that allowed backward selection. Baseline characteristics included in the model were: age, gender, indication, medical history, concomitant medications and comorbid conditions. To account for differences in pt baseline characteristics between pancreatitis and random CRs, an adjusted analysis was performed using inverse probability treatment weighting to reduce biases on estimates of average group (gp) effects. A p value below 0.05 was considered statistically significant.

Results
Over the approximate 7 years since regulatory approval of VDZ, 196 pts reported pancreatitis. A higher proportion of pts reported SAEs in the pancreatitis gp (99.5%, n=195/196) vs the random gp (32.5%, n=195/600). An unadjusted comparison between pts with SAEs showed that females (p=0.015) and Crohn’s disease (p=0.001) were more common in the random gp vs the pancreatitis gp. In the pancreatitis gp, 17 pts (8.7%) with SAEs had a known history of pancreatitis vs none in the random gp. Fourteen pts (7.2%) with SAEs had concurrent cholelithiasis in the pancreatitis gp vs none in the random gp. Results of the logistic regression analysis are shown in the Table. A number of factors, including age, VDZ indication use, the use of concomitant medications, a history of pancreatitis and several comorbid conditions strongly associated with the development of pancreatitis.

Conclusion
This retrospective analysis identified several factors associated with 196 spontaneous CRs of pancreatitis captured in our large GSD of over 700,000 patient-years of exposure to VDZ. This offers useful insights into potential predictive factors that could be important to inform clinical management of patients with IBD regarding the risk of pancreatitis, but further research to confirm these observations is warranted.
P647 Idiopathic Thrombocytopenic Purpura associated with Inflammatory Bowel Disease: a multi-centre ECCO CONFER case series
Authors: Mahajna H , Verstockt B , Bergemalm D , Castiglione F , Rodríguez-Moranta F , Vincenzo Savarino E , Hoentjen F , Bessissow T , Pokryszka J , Cremer A , Eder P , Truyens M , Yershalmy-Feler A , García M J , Kopylov U 
Published: January 2022

Abstract

Background
Idiopathic Thrombocytopenic Purpura (ITP) is an acquired haematological disorder with an incidence of 1 to 6 per 100.000, with reported comorbidity in patients with Inflammatory Bowel Disease (IBD). The current study aimed to evaluate the clinical presentation and outcome of ITP in IBD patients.

Methods
This multicenter retrospective case series was performed as part of the ECCO Collaborative Network of Exceptionally Rare case reports (CONFER) project. Cases of patients with ITP and IBD were collected by participating investigators. Clinical data were recorded in a standardised collection form.

Results
This report includes 20 patients with concurrent ITP and IBD: 15 were males, median age was 34 [Interquartile range (IQR) 25–56]. 12 subjects had a diagnosis of ulcerative colitis and 8 of Crohn’s disease. The diagnosis of IBD preceded the ITP diagnosis in 17 patients (median time between diagnosis was 7 years [IQR 1–14 years]). Among those, 10 patients were in IBD clinical remission at ITP diagnosis. Nine were treated with mesalamine, one with thiopurine, 4 with tumor necrosis factor-alpha (TNF) blockers, and 3 with no treatment. The mean platelet count at the presentation of ITP was 41.7±38.6 ×109/L. 6 patients had rectal bleeding, 8 had purpura, 6 had mucosal petechia, 2 had epistaxis, and 6 patients were asymptomatic. Regarding ITP treatment, 11 were treated with corticosteroids, 1 with Anti-RhD immunoglobulin, 7 with intravenous immunoglobulins (IVIG), 2 with rituximab and 2 patients eventually required splenectomy. All patients whose first presentation of ITP was rectal bleeding were treated medically with successful control of the ITP and IBD, None of them required splenectomy. 3 patients required colectomy with long-term follow-up, indicated by the IBD and not due to massive bleeding as a complication of ITP. With long-term follow-up, all patients had thrombocytes count above 50 ×109/L, and 18 were in IBD clinical remission.

Conclusion
Most ITP cases in this case series occurred after the IBD diagnosis and responded well to regular ITP treatment. The course of the ITP in the IBD patients follows a regular course, including response to medical therapy and low rates of splenectomy.
P648 Prevalence and Impact of Alcohol Consumption and Cannabis Use on Inflammatory Bowel Diseases
Authors: Martinho-Grueber M , Kapoglou I , Bravo F , Sarraj R , Benz E , Restellini S , Biedermann L , Rogler G , Vavricka S R , Schoepfer A , Maillard M , Michetti P , Brunner F , Clair C , Barry M P , Von Kaenel R , Juillerat P 
Published: January 2022

Abstract

Background
There is little guidance regarding the impact of alcohol and cannabis on the clinical course of inflammatory bowel disease. The aim of this study was to assess the prevalence, sociodemographic characteristics and impact of alcohol and cannabis use on the clinical course of the disease.

Methods
We performed a retrospective analysis of prospectively collected data within the Swiss Inflammatory Bowel Disease Cohort Study with yearly follow-ups and substance specific questionnaires. We analyzed the prevalence of use, profile of users at risk for addiction and the impact of alcohol and cannabis on the course of disease.

Results
We collected data of 2828 patients included between 2006 and 2018, and analyzed it according to their completion of specific surveys on alcohol and cannabis use. The prevalence of patient-reported active use was 41.3 % for alcohol and 6% for cannabis. Heavy drinkers were over-represented among retired, married smokers receiving mostly aminosalicylates and less immunosuppression. In ulcerative colitis patients, low-to-moderate drinking was associated with less extensive disease. Cannabis users were often students with ileal Crohn’s disease. A logistic regression analysis confirmed a risk of alcohol consumption in male workers &gt; 50 years, whereas cannabis use was only associated with nicotine consumption. Female gender, retirement and being married were protective factors regarding cannabis consumption.

Conclusion
A significant proportion of patients with inflammatory bowel disease consume alcohol or cannabis. Heavy alcohol consumption is most likely in male smokers &gt; 50 years, whereas young men with ileal disease rather use cannabis.
P655 Early life mebendazole exposure increases the risk of adult-onset ulcerative colitis: a population-based cohort study
Authors: Agrawal M , Allin K , Iversen A , Mehandru S , Colombel J F , Jess T 
Published: January 2022

Abstract

Background
According to the hygiene hypothesis, exposure to parasites may promote immune tolerance and protect against inflammatory bowel disease (IBD). The early life period, considered to extend from prenatal life to up to 5 years of age, is important towards immune maturation; exposures during this period are especially relevant towards IBD risk. We examined the impact of exposure to mebendazole, a broad-spectrum anthelminthic agent, during childhood and adolescence, on the risk of IBD, ulcerative colitis (UC) and Crohn’s disease (CD).

Methods
We used prospectively collected historical data of all individuals born in Denmark between 1995 and 2018 from national registers to conduct a population-based cohort study. Using the National Prescription Register, we identified mebendazole exposure at &lt;18 years of age, as well as at &lt;5 years of age. Using ICD8/10 codes in the cross-linked National Patient Register, we identified individuals who were subsequently diagnosed with UC or CD at &lt;16 or ≥16 years of age. We performed adjusted Cox proportional hazards regression analyses to determine the risk of IBD, UC and CD with mebendazole exposure after adjusting for potential confounders, which included calendar period, number of siblings and half-siblings, antibiotic prescription, sex, socio-economic status, degree of urbanization and parental IBD status.

Results
Of 1,520,290 individuals in the cohort, 615,794 had childhood mebendazole exposure. 1,555 and 1,499 individuals were subsequently diagnosed with pediatric- and adult-onset IBD, respectively. On multivariable analysis, mebendazole exposure at &lt;18 years of age did not impact pediatric- or adult-onset IBD risk (aHR 0.97, 95% CI 0.87, 1.07 and 1.08, 95% CI 0.97, 1.19, respectively) (Table). On limiting mebendazole exposure to age &lt;5 years, while there was no association with pediatric-onset IBD (aHR 0.98, 95% CI 0.87, 1.11), adult-onset IBD risk was increased (aHR 1.17, 95% CI 1.04, 1.31). This increase in risk was driven by UC (aHR 1.32, 95% CI 1.12, 1.55), but not CD (1.03, 95% CI 0.87,1.22) (Figure)
Table: Crude and adjusted estimates for outcome with exposure to mebendazole in early life (&lt;5 years of age)

Figure: Cumulative incidence curves for (a) ulcerative colitis and (b) Crohn’s disease

Conclusion
Early life, but not later in childhood or adolescence, mebendazole exposure is associated with increase in the risk of adult-onset UC. Mebendazole exposure does not impact pediatric-onset IBD risk or CD risk. These findings emphasize the importance of early-life exposures in shaping the risk of IBD later in life, may indicate differences between UC and CD risk factors and pathways, and may call for re-evaluation of risks and benefits of large-scale helminth eradication programs.
P674 Predictors of response to biologics in Crohn’s Diseases: A population-based study from the epi-IIRN
Authors: Atia O , Lujan R , Greenfeld S , Kariv R , Matz E , Dotan I , Nevo D , Turner D 
Published: January 2022

Abstract

Background
Approximately one third of patients with inflammatory bowel disease (IBD) fail to response to anti TNF drugs, and another 25–50% loses response within one year. Identifying prognostic factors of therapeutic failure, may facilitate balancing the risks and benefits of this therapy. In this population-based study, we aimed to explore predictors of therapeutic failure of biologics in Crohn’s disease (CD).

Methods
We retrieved data from two of four Health Maintenance Organizations in Israel, covering 38% of the population as part of the validated epi-IIRN IBD cohort. We included an inception cohort of CD patients, diagnosed since 2005 who were commenced on biologics. Those who underwent CD-related surgery within 90 days from diagnosis were excluded. The primary outcome was therapeutic failure (i.e. discontinuation of treatment or need for surgery or &gt;1 short steroid courses). The secondary outcome was primary non-response (PNR; i.e. therapeutic failure within 4 months of initiation). Predictors were sought through Cox proportional hazard model.

Results
A total of 2,805 patients were included (923 [33%] pediatric-onset, 1,882 [67%] adults) with a median follow-up of 7.5 years (IQR 4.4–11.5). The probability of of PNR was 11% and of therapeutic failure 29%, 52% and 62%, after one, three and five years after commencing biologics, respectively. Female sex (HR 1.2 [95%CI 1.1–1.4]), intestinal surgery prior to biologic treatment (HR 1.5 [95%CI 1.1–1.8]) and number of flares prior to biologic treatment (HR 1.1 [95%CI 1.1–1.2]) were associated with therapeutic failure. PNR was associated with intestinal surgery (HR 2.0 [95%CI 1.3–2.9]) and steroid use (HR 1.7 [95%CI 1.3–2.2]). Laboratory blood work, including CRP, ESR, albumin, hemoglobin, leukocytes and platelets, at diagnosis (HR 0.8 [95%CI 0.4–1.5]) and at initiation of biologics (HR 1.1 [95%CI 0.6–1.9]) did not predict therapeutic failure in the multivariable model.

Conclusion
Half of CD patients failed to response to biologic treatment within three years. Disease severity prior to biologic treatment, reflected by intestinal surgeries, number of flares and steroid use, predicted therapeutic failure. These results emphasize the importance of timely introduction of intensified treatment in patients at risk.
P677 Patients with Inflammatory Bowel Diseases on anti-TNF treatment have impaired antibody production after Anti-SARS-CoV-2 vaccination: Results from a Panhellenic registry
Authors: Zacharopoulou E , Orfanoudaki E , Kitsou V , Tzouvala M , Tribonias G , Mantzaris G J , Viazis N , Christidou A , Almpani F , Karmiris K , Theodoropoulou A , Tsafaridou M , Michopoulos S , Zampeli E , Papathanasiou E , Michalopoulos G , Tigkas S , Karatzas P , Laoudi E , Liatsos C , Kyriakos N , Mylonas I , Theocharis G , Koutroubakis I E , Bamias G 
Published: January 2022

Abstract

Background
The novel corona virus (SARS-CoV-2) outbreak was declared as a pandemic in March 2020; this prompted the need for rapid vaccine development. Currently four EMA approved vaccines exist but their efficacy and safety data on patients with Inflammatory Bowel diseases are limited.

Methods
Greek IBD patients, from 10 tertiary referral centres, who had completed the initial vaccination protocol with the available anti-COVID-19 vaccines at least two weeks before enrolment, were prospectively studied. Demographic and safety data were collected and blood samples were drawn for serum Anti-S1 IgG measurement [Euroimmun Anti-SARS-CoV-2 QuantiVac ELISA (IgG)].

Results
In total 403 IBD patients (59% Crohn’s disease, median age 45 years, 53% male) and 124 healthy controls (HC) were included (Table 1). Antibody testing was conducted after a median of 31 (IQR, 23–46) days post-vaccination. Following a full vaccination regimen, 98% of IBD patients seroconverted (anti-S1 IgG≥11 RU/ml). Administration of mRNA vaccines resulted in higher seroconversion rates and higher antibody titers than viral vector ones (98.6% vs 93.6%, P=0.02 and 111.2 RU/ml vs 76 RU/ml, P&lt;0.0001, respectively). In total, IBD patients had lower anti-S1 levels than HC (RU/ml 108 vs 133 RU/ml, P=0.00009). IBD patients without immunosuppression had higher antibody titers than immunocompromised patients (P=0.012). In univariable analysis, older age, longer time since vaccination, and treatment with corticosteroids, immunomodulators, anti-TNFα or combination therapy were associated with lower anti-S1 titers. In contrast, higher anti-S1 levels were detected in patients on vedolizumab monotherapy or non-immunosuppressive treatment. In multivariable analysis, only age, time since vaccination, and anti-TNFα therapy remained significant (P=0.011, P=0.002, and P=0.013 respectively). Treatment with vedolizumab monotherapy was associated with higher antibody levels than anti-TNFα or ustekinumab monotherapy (P=0.023 and P=0.032). Patients with prior COVID-19 infection showed numerically higher levels of Abs. All vaccines were safe in IBD patients.

Conclusion
Patients with IBD have high seroconversion rates to anti-SARS-CoV-2 vaccines, with mRNA vaccines being more efficacious. However, IBD patients have impaired response to vaccination comparing to HC. Lower antibody responses were observed in patients who received viral vector vaccines, in older patients, and in those on anti-TNFα treatment. It is important to consider booster vaccination in those low-response groups.