bluuebunny/crossref_metadata_2025_split huggingface dataset:
P566 Humoral immune response to mRNA COVID-19 vaccine in Puerto Ricans with IBD does not differ between class of biologics
Authors: López Marte P , Ramos-Tollinchi L , Rodriguez-Martinó E , Medina-Prieto R , Ojeda S , Santana-Bagur J , Pantoja P , Sariol C A , Torres E A 
Published: January 2022

Abstract

Background
The COVID-19 vaccine trials did not include subjects with IBD or immunosuppression, limiting the effectiveness data of the vaccine in this population. The impact of biologics with different mechanisms of action on antibody concentrations and neutralizing capacity produced by the vaccine may alter prevention strategies. We aim to describe a comparison of the humoral response to COVID-19 vaccine in patients with IBD on biologics between different therapies and a control group.

Methods
Patients ≥21 years of age with Crohn’s disease (CD) and ulcerative colitis (UC) on biologic therapy were recruited. Blood samples were collected at 14 ± 2 days (Cohort 1) and 60 ±7 days (Cohort 2) after receiving a 2nd dose of mRNA COVID-19 vaccine [BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna). Anti-spike protein receptor binding domain IgG levels and neutralizing capability using SARS-CoV-2 surrogate virus neutralization test (sVNT%) were measured. A result &gt;30% is positive for effective viral inhibition. Results were stratified by mechanism of action of the drug and compared with a healthy control group. Comparisons were evaluated by Kruskal-Walls test and Dunns Pairwise/Bonferroni. The study is approved by the MSC IRB.

Results
32 subjects exposed to biological therapy divided into 2 cohorts (14-days, n=19/60-days, n=13) and 18 samples of healthy controls (14-days, n=12/60-days, n=6) are reported. Of the IBD subjects, 81% (26/32) had CD, 56% were males (18/32) and mean age was 39. All subjects were receiving biological monotherapy, one subject was also on azathioprine. All groups developed detectable antibody levels and &gt;60% neutralizing antibody detection after 14 and 60 days of the second vaccine dose. IgG levels at 14 days (p&lt;0.001) and sVNT% at 14- and 60-days post second vaccine dose (p=0.007, 0.024) were significantly different between subjects vs. controls. When stratified by mechanism of action, there was a significant difference between each biologic vs. control (p&lt;0.001), but no difference between biologic classes. Initial analysis for the sVNT% at 14 days showed statistical significance (p=0.046). Post-hoc analysis showed no statistical significance in the individual comparisons. No significant differences were found between each therapy vs. control for IgG levels nor sVNT% at 60-days (p=0.257, 0.113).

Conclusion
Our study shows that IBD patients on biological therapy who receive a COVID-19 vaccine develop a lower but effective humoral response up to 60 days after the second dose when compared to healthy individuals. No difference was found between class of biologics. A larger sample is needed.
P567 Safety analysis of tofacitinib in ulcerative colitis: Real-world outcomes from a three-year UK observational cohort study
Authors: Honap S , Sharma E , Ray S , Mawdsley J , Anderson S , Samaan M , Pavlidis P , Irving P 
Published: January 2022

Abstract

Background
Serious adverse events (SAE), including venous thromboembolism (VTE) and major adverse cardiovascular events (MACE), have been reported in tofacitinib post-marketing trials. However, safety data extending beyond six months in the real world are scarce.1 We explored the incidence rates (IR) of adverse events (AE) in a tofacitinib-treated cohort of ulcerative colitis (UC) patients at a large tertiary centre over three years.

Methods
We conducted a retrospective analysis of a prospectively maintained database of consecutive patients commencing tofacitinib from October 2018 to October 2021. AE details were extracted from elective and emergency visits during induction and maintenance treatment. SAEs were defined as AEs that were life-threatening or required hospitalisation. We also assessed changes in haematological and biochemical parameters, including lipid levels, during treatment. Exact Poisson confidence intervals (CI) (adjusted for PYs) were calculated to determine IRs and univariate analyses and multivariate logistic regression were performed to examine AE risk factors.

Results
A total of 103 patients were studied with a median follow up duration of 53 weeks (range 1–156). Median treatment duration on 10mg bd was 18 weeks (range 1–135). AEs and SAEs were recorded in 37% and 16% of the study cohort, respectively, over 118 PYs exposure. Infection was the most common AE and hospitalisation for disease progression requiring colectomy while on tofacitinib was the most frequent SAE (table 1). Overall, the IR for SAEs was 13.6 per 100 PYs (95% CI 9.1–26.0) (table 2). Single dermatomal herpes zoster (HZ) reactivation (including one case of HZ opthalmicus) occurred in 5%; all occurred on 10mg BD dosing, and all were successfully treated with antiviral therapy. Duration of high dose tofacitinib treatment, age, weight, concomitant corticosteroid use, and prior TNF exposure were not associated with AEs. Although there was a significant increase in total cholesterol (TC) and low-density lipoproteins, the TC to high-density lipoprotein ratio remained unchanged (table 3) and no patient required the introduction of a lipid lowering agent. Tofacitinib was well tolerated and excepting treatment discontinuation due to drug failure requiring surgery, AEs resulted in tofacitinib withdrawal in only one patient (headaches). There were no cases of MACE or VTE.

Conclusion
Although a third of our cohort had AEs, tofacitinib-treatment failure and subsequent hospitalisation and surgery was the most frequently occurring. No new safety signals were identified with extended real-world follow up.

Reference
1. Taxonera C et al. Real-World Effectiveness and Safety of Tofacitinib in Patients With UC: Systematic Review and Meta-Analysis. Inflamm Bowel Dis. 2021
P591 Biological therapies and small molecules show to be efficacious in patients with moderate-to-severe ulcerative proctitis
Authors: Lemmens P , Guedelha Sabino J , Dubois E , Verstockt B , Vermeire S , Ferrante M 
Published: January 2022

Abstract

Background
Although adalimumab (ADM), golimumab (GOL), infliximab (IFX), tofacitinib (TFC), ustekinumab (UST) and vedolizumab (VDZ) have been shown efficacious for the treatment of moderate-to-severe ulcerative colitis (UC), data on treatment of patients with ulcerative proctitis (UP, inflammation up to 15cm from the anal verge) are scarce. We therefore aimed to evaluate the effect of these advanced therapies on UP.

Methods
We conducted a retrospective study in which we included 74 patients (median age at induction 41 (IQR 32–52) years) with active UP (Mayo endoscopy sub-score of ≥2) initiating a biological therapy (ADM, GOL, IFX, UST, and VDZ) or small molecule (TFC) in our tertiary referral centre between 02-2005 and 02-2021. The primary endpoint was steroid-free clinical remission at week 20 without prior need for dose optimization. Clinical remission was defined as a total Mayo score ≤2 with no individual sub-score &gt;1. We also evaluated clinical response at short-term follow up (FU), as well as outcomes at long-term FU. The adapted Mayo score (sum of stool frequency subscore and rectal bleeding subscore) was used to rate the long-term treatment outcome, since colonoscopy was not routinely performed. We collected demographic, clinical, biochemical, endoscopic and treatment-related data.

Results
In total 74 patients (57% male) undergoing 93 courses of therapy for UP (16 ADM, 5 GOL, 19 IFX, 4 UST, 44 VDZ, 5 TFC) were included. In Table 1 the baseline characteristics are displayed. At week 20, 31/93 (33.3%) patients achieved steroid-free clinical remission, and 48/93 (51.6%) patients achieved steroid-free clinical response, both without prior need for dose optimization (Table 2). No predictors of steroid-free clinical remission could be identified. Of the 93 patients 91 had a FU under the index-therapy beyond week 20. The median duration of FU was 15.5 (IQR 3–31) months. Of the 31 patients with initial steroid-free clinical remission, 26 patients (83.8%) had sustained steroid-free clinical remission. The treatment-discontinuation-free survival of the entire study population is shown in Figure 1. Only one patient developed a serious adverse event, namely a tuberculosis infection.

Conclusion
Biological therapies and small molecules are a safe treatment for patients with UP, with an overall steroid-free clinical remission rate of 34.4% (32/93) at short-term FU. Our results are lower than in previous studies, probably because of the more stringent definitions of clinical remission and response.
P599 Azathioprine in the prevention of anti-infliximab antibody formation: A pilot dose-finding study
Authors: Kojecký V , Wasserbauer M , Keil R 
Published: January 2022

Abstract

Background
The infliximab (IFX) therapy is associated with production of the anti-IFX antibodies (ATI), that can lead to infusion reactions and affect the therapeutic response. Concomitant use of azathioprine (AZA) in patients treated with IFX is recommended. A lower dosage is suggested however without further specification. The aim of this study is to determine the threshold dose of AZA to prevent ATI formation during IFX therapy.

Methods
The Retrospective, multicenter (Zlin, Prague, Czech rep.), observational study. The adult patients with ulcerative colitis or Crohn’s disease, treated with IFX in scheduled regimen (5mg/kg á 8 weeks), on concomitant azathioprine therapy (&gt; 3 month), without any other immunomodulator or steroids, who were tested for IFX and ATI levels, were enrolled. The primary outcome measure was the dose of AZA and ATI positivity (cut-off &gt; 3 AU/ml), secondary measure included interval to the appearance of ATI. ROC analysis was used to evaluate AZA dose and interval predictive of the ATI positivity.

Results
Of the 62 patients analyzed (53% female, mean age 34.1 years), 76% had Crohn’s disease. 29 (47%) subjects were treated with biosimilar IFX. The mean dose of AZA was 1.5 ± 0.5 mg/kg, and the duration of IFX treatment was 44.2 ± 41.4 months. ATI ′s were present in 23 subjects (37.1%), with no difference between original and biosimilar IFX. ATI positivity was associated with lower mean IFX levels (1.8 ± 2.4 vs 6.0 ± 5.1ug/ml, p=0.002). The threshold dose of AZA for ATI positivity was predicted to 1.2 mg/kg (95% CI 0.6–1.8, p=0.02, AUC 0.682) and the time to antibody appearance to 13.0 months (95% CI 5.0–49.1, p=0.02, AUC 0.672).

Conclusion
The dose of AZA lower than 1.2 mg/kg was associated with a higher chance of anti-IFX antibodies development. Their appearance may be expected after 1 year from the initiation of the combo IFX therapy. ATI′s are associated with reduced IFX through levels.
P600 Serologic response to COVID-19 vaccines in IBD patients: a prospective study
Authors: Martin Arranz M D , García Ramírez L , Montero Vega D , Martín-Arraz E , Sánchez Azofra M , Poza Cordon J , Rueda Garcia J L , Noci Belda J , Verges Martínez-Meco T , Blanco San Miguel P , Suarez Ferrer C 
Published: January 2022

Abstract

Background
Our objective is to evaluate the serologic response to the SARS-CoV-2 vaccine in patients with Inflammatory Bowel Disease (IBD). In addition to that, we want to analyze the influence of immunosuppressive drugs in that response, as well as describe the adverse events in this population.

Methods
We included 266 patients in a unicentric prospective study. All patients signed informed consent. A serologic blood test was made days before the first dose and 2–4 weeks after the complete immunization. We used Siemens Atellica Anti-SARS-CoV-2 (N) and Vircell Virclia (S and N) electrochemiluminescence immunoassay to detect antibodies to SARS-CoV-2). If they were discordant, the results were considered as undetermined. The IBD treatment was stable along the study. The statistics analysis of data was done with Stata 16.

Results
Basal characteristics are described in table 1. The patients were on treatment with: 15 (5.66%) had no treatment, 47 (17.7%) had mesalamine, 4 (1.51%) had corticosteroids, 41 (15.47%) had immunomodulator, 113 (42.64%) had biologic and 45 (16.98%) had combo. Amongst the biologic drugs: Infliximab 51 (32,3%), Adalimumab 50 (31,6%), Vedolizumab 19 (12,03%) y Ustekinumab 31 (19,6%). The vaccines were messenger RNA BNT162b2 (Pfizer-BioNTech) in 154 patients (58%), AZD1222 (Oxford-Astra Zeneca), in 80 patients (30%), messenger RNA-1273 (National Institutes of Health [NIH]-Moderna) vaccines in 19 patients (7%) and Ad26.CoV2.S (Janssen) in 13 patients (5%). 72.7% after first dose and 86% after second experienced side effects, with no severe cases (see table 2). Depending on the administered vaccine we can see 80% with Pfizer, 93.3% using Moderna, 49% with Astrazeneca and 100% using Janssen. This differences reached statistical significance (p=0.02). In the first blood test 222 (85%) patients tested negative, 27 patients positive (10.34%) and 12 patients undetermined (4.6%). Patients with a previous positive test were excluded. After the vaccination, 92.5% of our patients (233) had positive antibodies against SARS-COV2, a 4,75% (12 patients) undetermined titles, and a 2.75% (7 patients) were negative. In table 3we show the seroprevalence with different treatments. When analysing the antibody formation depending on the vaccine administered we can see: Pfizer 92.9%, Moderna 93.3%, Astrazeneca 98.4%, Janssen 12.5% (75% indetermined) (p&lt; 0,0001)

Conclusion
The antibody response following Sars-CoV-2 vaccination is high in IBD patients. However, patients treated with inmunosupresive or biologic drugs (except vedolizumab) have a lower response and is significantly lower with the Ad26.CoV2.S (Janssen) vaccine, which could influence future doses. Adverse events are frequent but not severe.
P610 Safety of COVID-19 vaccine in patients with Inflammatory Bowel Disease: preliminary data of a national study (ESCAPE-IBD)
Authors: Todeschini A , Macaluso F S , Contaldo A , Mannino M , Orlando A , Principi M 
Published: January 2022

Abstract

Background
Vaccination is the most effective method to prevent and control the SARS-CoV-2 infection. Recommendations consider patients with inflammatory bowel disease (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), a high-priority population to COVID-19 vaccine administration. There were a lot of concerns about vaccination safety in the setting of biological and immunomodulatory drugs. The purpose of this study was to present data on safety about anti-SARS-CoV-2 vaccination in a cohort of IBD patients. These are preliminary data of an ongoing multicenter study assessing effectiveness and safety of COVID-19 vaccines in patients with IBD treated with immunomodulatory or biological drugs (ESCAPE-IBD) sponsored by the Italian Group for the study of Inflammatory Bowel Disease (IG-IBD - ClinicalTrials.gov Identifier: NCT04769258).

Methods
Anti-SARS-CoV-2 vaccine (Pfizer-BioNTech®) in two shots were administrated to 427 IBD patients. Afterwards completed vaccination, telephone or in-person interviews were conducted from February to July 2021 by gastroenterologists from referral center to report local and/or systemic adverse events (AEs) related to vaccination. Data on medical history and treatment was collected from electronic health records. Chi-square test was used to compare categorical variables. Logistic regression was used to assess the relationship between disease-related characteristics and the onset of AEs.

Results
427 patients, 252 CD and 175 UC, were enrolled. All patients received two shots of SARS-CoV-2 vaccine. AEs were more common in females (70% vs 50% male gender; p&lt;0.001). Most of them (75%) were in biological or immunomodulatory therapy. About 58% of patients had at least one side effect, following the first dose (13%), the second (22%) or both doses (23%). Local pain at site of injection (31%), fatigue (19%) and fever (15%) were the three most common AEs. Flares of the underlying IBD were not reported. The vast majority of AE were mild and lasted only a few days. No serious AEs were reported and no patient was hospitalized. Logistic regression analysis revealed that female gender (p&lt;0.001) and younger age (p=0.016) were significantly associated with the occurrence of AEs.

Conclusion
The short-term vaccine reactions experienced in this cohort of IBD patients were mostly self-limiting, including local pain at the injection site, fatigue and fever. We found a good safety profile of SARS-CoV-2 vaccination in our cohort.
P636 Work disability after 20 years with Inflammatory Bowel Disease - results from the IBSEN study
Authors: Lund C , Kristensen V A , Monstad I L , Solberg I C , Hovde Ø , Huppertz-Hauss G , Henriksen M , Høie O , Bernklev T , Jahnsen J , Moum B , Høivik M L 
Published: January 2022

Abstract

Background
At the 10-year follow-up in the IBSEN (Inflammatory Bowel in South-Eastern Norway) study, there was an increased relative risk of permanent work disability for patients with inflammatory bowel disease (IBD), compared with the age-matched background population. Now we aimed to assess the prevalence of work disability benefits among Crohn’s disease (CD) and ulcerative colitis (UC) patients 20 years after diagnosis, using data from the IBSEN study and the Norwegian Registry for social security benefits (FD-Trygd).

Methods
In the IBSEN study the participants have had planned a scheduled follow-up visit after 1-, 5-, 10- and 20-years. At the 20-year follow-up, they received a questionnaire about temporary and permanent work disability benefits and those who answered at least one of the questions were included in this study. Patients above 67 years of age (i.e. the standard retirement age in Norway) at the time of diagnosis were excluded. From FD-Trygd, we acquired officially registered information about the patients’ work disability status. UC and CD patients were compared using the Pearson’s Chi-squared (χ 2) test for categorical variables and the Mann-Whitney U test for continuous variables.

Results
A total of 421 patients attended a 20-year follow-up and information from 418 were included for analysis. Out of those, 281 had UC (51.2% women) with a median age at the 20-year follow-up of 54.3 years (range 29.5–85.2) and 137 had CD (49.6% women) with a median age of 47.8 (range 27.4–84.8). At the 20-year follow-up, 38.1% of the IBD patients (UC 34.9% and CD 44.6%, p=0.061) reported that they had applied for and/or received temporary or permanent work disability benefits. In total 20.3% (UC 18.3% and CD 24.4%, p=0.181) reported they had been granted a permanent work disability benefit, while 10.2% reported that this was due to their IBD (UC 8.2% and CD 14.2%, p=0.067). In FD-Trygd, 27.3% of the IBD patients in the IBSEN cohort (UC 26.3%, CD 29.2%, p=0.537) were registered as having been granted permanent work disability benefits during the 20-year period.

Conclusion
Every fifth patient reported that they had been granted permanent work disability benefits after 20 years with IBD, but this was related to other diseases (or reasons) in half of them. According to FD-Trygd, however, more than one in four patients had been granted permanent work disability benefits in the same time-period. While differences between the UC and CD patients were found to be insignificant in these data, the difference between patient-reported and registry data is important for further socio-economic analyses and should be examined more closely.
P639 Incidence and disease presentation of inflammatory bowel disease in Denmark: initial findings from a Copenhagen IBD Inception Cohort Study
Authors: Dorn-Rasmussen M , Attauabi M , Madsen G R , Wewer A V , Jansson S , Knudsen M M , Wilkens R , Ilvemark J F K F , Bjerrum J W , Theede K , Bendtsen F , Trine B , Seidelin J B , Burisch J M 
Published: January 2022

Abstract

Background
Denmark has one of the highest occurrences of inflammatory bowel disease (IBD) in the world, with reported incidence rates of 7.2 and 6.2 in paediatric ulcerative colitis (pUC) and 10 and 9.4 per 105 for girls and boys in Crohn’s disease (pCD). Incidence rates in adult patients have been reported to be 9.1 and 18.6 per 105 for ulcerative colitis (UC) and Crohn’s disease (CD), respectively. We aimed to evaluate the incidence and initial disease presentation of newly diagnosed paediatric and adult IBD patients in the Hvidovre and Herlev Hospital uptake areas, covering approximately 1.050.000 inhabitants, corresponding to ~20% of the Danish population.

Methods
During a 2-year inclusion period, all incident paediatric (≤18 years of age, pIBD) and adult IBD patients residing in the uptake area at the time of diagnosis are included in a prospective, multicentre, population-based inception cohort (IBD Prognosis Study). The study was initiated on May 1st, 2021. Patients are prospectively followed with regular intestinal biopsies, stool-, serum-, and whole blood samples to analyze biomarkers, microbiome and genetic profiles at predefined time points. Demographics and disease-related characteristics were collected at diagnosis. Incidence was defined as the number of new IBD cases during May 1st – October 31st divided by the total inhabitants covered in included sites during the same period.

Results
A total of 125 IBD patients were included during the initial six months (table 1). For paediatric patients, the incidence rates were 8.2 and 16.4 per 105 for pUC and pCD. Adult incidence rates were 19.4, 17.0, and 2.4 per 105 for UC, CD and IBD-unclassified (IBD-U), respectively. At diagnosis, extraintestinal manifestations were present in 15% of paediatric and 36% of adult patients. In paediatric patients, 20% and 0% of pUC and pCD had moderate to severe disease activity at diagnosis, based on PUCAI- and PCDAI scores. In adults, 33%, 50% and 50% of UC, CD and IBD-U patients had moderate to severe disease activity at disease onset based on SCCAI- and HBI scores. More extensive disease and increased faecal calprotectin were associated with more severe disease activity in adult UC. CRP correlated positively, while haemoglobin and albumin correlated negatively with UC disease extension.

Conclusion
The IBD incidence rates in paediatric and adult patients continuously increase in Denmark, thus constituting a substantial burden for the Danish health care system. A large proportion of patients presented with significant symptoms and future findings of this cohort will potentially bring us a better understanding of the heterogeneous course of IBD, including the differential need for, and response to, treatment.