bluuebunny/crossref_metadata_2025 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

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 >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 >60% neutralizing antibody detection after 14 and 60 days of the second vaccine dose. IgG levels at 14 days (p<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<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

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

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 >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

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 (> 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 > 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

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< 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

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<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<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

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

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.
P642 Crossroads of vitamin B6 deficiency and inflammation in inflammatory bowel disease: Preliminary results of a cross-sectional study
Authors: Farrag K , Woldeab J , Stein J M , Aksan A
Published: January 2022

Background

The robust relationship between vitamin B6 and inflammation has become apparent over the last decade. However, the mechanistic nature of this relationship remains unclear. Evidence suggests an inverse relationship between blood levels of B6 and inflammation, but also a potential two-way relationship between the two. Thus, whereas inflammation can deplete serum vitamin B6, vitamin B6 insufficiency can attenuate inflammation. This study aimed to assess vitamin B status in patients with IBD in routine clinical practice and identify possible relationships between vitamin B6 status and clinical disease characteristics.

Methods

In a comparative, retrospective cross-sectional study, serum samples of patients with IBD were studied. CBC, albumin and hsCRP were determined and samples assessed for presence/absence of inflammation (serum hsCRP, cut-off <5mg/L). Vitamin B6 status was determined via direct measurement of pyridoxal 5′-phosphate (PLP) by enzymatic assay.

Results

149 patients with IBD (64f/85m; 82CD/67UC; 39.9±14.6y) were included. Of these, 44/149 had inflammation (19f/25m; 22CD/22UC; 41.2±14.9y) and 105/149 no inflammation (45f/60m; 60CD/45UC; 39.3±14.4y). In patients with inflammation, mean serum PLP levels were significantly lower (7.2[1.9–46.0] µg/L) vs. patients without inflammation (9.8[0.1–88.0] µg/L) (p<0.05). Accordingly, vitamin B6 deficiency occurred significantly more frequently in patients with vs. without inflammation (34.1% vs. 19.0%, p<0.05). A higher incidence of vitamin B6 deficiency was seen in patients with CD vs. UC, though without statistical significance (26.8% vs. 19.4%, p>0.05). The frequency of vitamin B6 deficiency did not differ according to disease localisation (p>0.05). Serum PLP levels inversely correlated with the inflammatory markers hsCRP and ESR (r=-0.306, p<0.001 and r=-0.203, p<0.001, respectively). Furthermore, there was a significant positive correlation between blood PLP levels and other selected acute-phase reactants, e.g., TSAT% (r= 0.207, p<0.05). However, no significant correlation was found with ferritin (r=-0.152, p=0.064).

Conclusion

Low serum total vitamin B6 levels were associated with inflammation but not disease type or localisation in patients with IBD. In line with preclinical findings and previous observational studies, vitamin B6 deficiency was more pronounced in patients with inflammation. Our findings suggest vitamin B6 may have a bigger role than thought in IBD; besides its relationship with inflammation, a possible involvement of vitamin B6 deficiency as cause or effect in IBD pathogenesis warrants investigation. Routine assessment and correction of vitamin B6 status may ameliorate IBD and help maintain intestinal integrity.
P657 Persistence in smoking cessation in inflammatory bowel disease (IBD)
Authors: González Muñoza C , Gely C , Teller M , Mombiela A , Roig C , Lopez-Faba A , Bertoletti F , Gordillo J , Garcia-Planella E
Published: January 2022

Background

Smoking Habit (SH) is a relevant epidemiological factor in IBD, so it is recommended to quit. We have no data on the persistence of its long-term abandonment.

Methods

All patients of our hospital registred in the ENEIDA registry (spanish national IBD registry) with active SH at time of diagnosis were identified. Ex-smokers (> 6 months of abstinence) were invited to participate by telephone contact and epidemiological and SH data were recorded using medical records and telephone survey. The Fargeström Test for Nicotine Dependence (FTND) was used to grade the degree of addiction.

Results

122 ex-smokers [88 Crohn Disease (CD), 33 Ulcerative Colitis (UC)] were included, the mean age of SH abandonment (SHA) was 41 years (33–48), lower in CD (38 years) compared to UC (46) (p-value 0.002). The mean time from diagnosis to SHA was 72 months in CD and 98 in UC. Patients had a 2-point degree of FTND addiction, higher in CD (p-value 0.063), with 80% of them working. In CD, the main motivation was medical indication as a specific treatment (28%) and for general health advice (23%); in UC were general health advice (45%) followed by associated comorbidities (15%). 90% of the cohort managed to quit smoking on their own and only 11% needed pharmacological help. 60% explained a relapse, on average at 12 months (3–36), with a higher rate in CD (46%) compared with UC (24%) (p-value 0.029) despite a longer mean follow-up of patients with UC (114 VS 168, p-value 0.035). 39% of them referred to be living with a smoker at the time of relapse. The only factor of those assessed that directly impacted the risk of relapse was a higher score on the FTND (p-value 0.027).

Conclusion

- The overall risk of relapse is 60%, half of which during the first year. Patients with CD have a higher risk, possibly due to a higher degree of addiction.

- The only factor associated with relapse in (SH) was a higher FTND score.

- SHA is delayed in relation to the diagnosis of IBD.
P662 Colorectal Cancer in Patients with Ulcerative Colitis: A National Cohort Study between 1991–2020
Authors: Heuthorst L , Harbech H , Snijder A , Mookhoek A , D’Haens G , Vermeire S , D’Hoore A , Bemelman W , Buskens C
Published: January 2022

Background

Studies on the colorectal cancer (CRC) risk in patients with ulcerative colitis (UC) show conflicting results. The aim of the current study was to assess if there is an indication shift for surgery in patients with UC from refractory disease to malignant degeneration over the last 3 decades.

Methods

From the nationwide Dutch Pathology Registry (PALGA), pathology excerpts from all patients with histologically confirmed UC who underwent a colorectal resection for all indications between January 1st, 1991 and November 12th, 2020 were included. The primary outcome was the CRC rate in the colon specimens. Outcomes were compared between 3 time periods (P1: 1991–2000, P2: 2001–2010, P3: 2011–2020).

Results

Overall, 6,094 UC patients were included of which 5,026 underwent a (procto)colectomy and 1,068 a segmental resection. In 1,031 (16.9%) patients, pathological examination demonstrated CRC after a median disease duration of 11 years [IQR 3.0–19.0]. The CRC rate in the colectomy specimen increased from 11.3% in P1, to 16.1% in P2, to 22.8% in P3 (p-trend <0.001). Compared to patients in P1, patients in P2 and P3 had a longer disease duration before resection (4 years [IQR 0.0–9.0] vs. 10 years [IQR 3.0–16.0] vs. 17 years [IQR 7.0–23.0], p<0.001). The proportion of patients diagnosed with advanced disease (pT3/T4) (P1: 61.2% vs. P2: 65.2% vs. P3: 62.4%, respectively, p=0.633) and lymph node metastasis (P1: 33.0% vs. P2: 41.9% vs. P3: 38.2%, respectively, p=0.113) did not decrease over time.

Conclusion

This nationwide pathology study demonstrated an increased surgical indication rate for CRC in UC patients over the last 3 decades. We hypothesize that the expanding therapeutic armamentarium for UC likely leads to exhausting medical options and hence postponed colectomy. This however, might be at the expense of increased risk of CRC in the long term. Despite the introduction of surveillance programs, the incidence of advanced colon carcinoma remains high.
P671 Occurrence and clinical impact of eosinophilic esophagitis in a large cohort of children with Inflammatory Bowel Disease
Authors: Aloi M , Rossetti D , Bucherini S , Felici E , Romano C , Martinelli M , Di Pasquale V , Lionetti P , Oliva S
Published: January 2022

Background

Scarce data have investigated the association between pediatric Inflammatory bowel disease (IBD) and Eosinophilic esophagitis (EoE). We, therefore, aimed to describe the epidemiology and a possible peculiar phenotype and natural history of such association.

Methods

Case-control study based on the Italian Society for Pediatric Gastroenterology (SIGENP) national registry. All children with a concomitant diagnosis of IBD and EoE were included. Overall prevalence and incidence in 2 periods, 2009–2015 and 2016–2021, were calculated. Cases were matched with IBD only and EoE only patients in a 1:3 ratio. Phenotype and outcomes (courses of steroids, risk of complications, surgery, treatment escalation, and hospitalization) were compared between groups.

Results

Eleven patient (age 11,27 ± 2,83, Male 91%) with EoE-IBD out of 3090 patients with IBD only were identified, resulting in a prevalence of 0,35% and an incidence of 0,18% for the period 2009–2015 and 0,45% for the period 2016–2021. Treatment escalation rates were significantly higher in patients with IBD compared to EoE-IBD at 12 and 24-month follow-up (0 vs 30%, p = 0.04 and 9% Vs 45,5%, p = 0.03, respectively). Patients with IBD only were at a significantly higher risk of hospitalization than both EoE-IBD and EoE only patients (Log Rank p < 0.001). We found no significant differences in major outcomes related to the EoE course in EoE-IBD patients compared to EoE patients.

Conclusion

Overall, the incidence and prevalence of EoE in children with IBD are low, although the incidence seems to be rising in the six years. Having an EoE appears to be associated with a milder IBD disease course while having an IBD doesn’t seem to affect the natural history of EoE. More data are needed to better define the phenotype of such condition.
P684 Increased risk of cardiovascular disease and high risk profiles compatible with metabolic syndrome in patients with Inflammatory Bowel Disease: a cross-sectional analysis of matched cohorts
Authors: Sleutjes J , Roeters van Lennep J E , Kavousi M , Aribas E , van der Woude C J , de Vries A C
Published: January 2022

Background

Patients with inflammatory bowel disease (IBD) have an increased risk of cardiovascular disease (CVD). This probably results from a cumulative effect of chronic inflammation and traditional CVD risk factors. We assessed the CVD risk profile of IBD patients as compared to the general population.

Methods

In this cross-sectional study, consecutive IBD patients aged ≥45 years were included at the Gastroenterology and Hepatology outpatient clinic. CVD risk profiles wese assessed by anthropometrics (blood pressure, length, weight, waist and hip circumference), serum analyses (nonfasting glucose and lipid spectrum) and self-administered questionnaires (history of CVD events, traditional CVD risk factors, medication use). One to four controls from the Rotterdam Study were matched to each IBD case by sex and age (scope +-5 years). Stratification was applied to asses differences between sex, IBD diagnosis and clinical disease activity (HBI or SCCAI>5).

Results

235 IBD patients were included (44% male; median age 59 years (IQR 51–66)) and matched to 829 controls (44% male; median age 62 years (IQR 57–68)). IBD patients were more frequently diagnosed with CVD (OR 2.01, 95%CI 1.23–3.27). IBD patients showed lower odds of overweight defined as BMI ≥25 kg/m2 (OR 0.48, 95%CI 0.35–0.66) and hypercholesterolemia defined as total cholesterol ≥6.2 mmol/L, self-reported diagnosis or use of lipid lowering drugs (OR 0.45, 95%CI 0.31–0.65). The following markers of metabolic syndrome were increased in IBD patients: hypertension defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, self-reported diagnosis or use of antihypertensive drugs (OR 1.67, 95%CI 1.19–2.32), waist circumference (92 cm (SE±10) vs 88 cm (SE±8), p=.006) and triglyceride level (2.7 mmol/L (SE±0.8) vs 2.1 (SE±0.8), p<.001). (Table 1) Male patients had higher waist circumference, less favorable lipid profiles and were more frequently diagnosed with hypertension (OR 1.72, 95%CI 0.99–2.94) as compared to female patients. Patients with ulcerative colitis were more frequently smokers (OR 4.34, 95%CI 1.27–16.66) and showed higher odds of hypercholesterolemia (OR 1.85, 95%CI 1.06–3.33) as compared to patients with Crohn’s disease.

Conclusion

Patients with IBD are more frequently diagnosed with CVD as compared to age-sex matched controls. The CVD risk profile in IBD patients is characterized by components of the metabolic syndrome, i.e. hypertension, truncal obesity and hypertriglyceridemia, particularly among male IBD patients. The prevalence of other traditional CVD risk factors was comparable or even lower in IBD patients as compared to controls. The exploration of targeted preventive management strategies is required.
P685 Strong Response to SARS-CoV-2 Vaccine Additional Doses among Patients with Inflammatory Bowel Diseases
Authors: Kappelman M , Weaver K , Zhang X , Chun K , Long M
Published: January 2022

Background

Current recommendations in many countries support additional COVID-19 vaccine doses in patients with inflammatory bowel disease (IBD) who are treated with immunosuppressants, yet real-world data on the effectiveness and safety of additional vaccine doses is lacking. We sought to quantify the humoral immune response to an additional vaccine dose in patients with IBD.

Methods

We performed a direct-to-patient, internet-based cohort study of patients with IBD in the United States who have received any SARS-CoV-2 vaccine granted EUA. Participants completed baseline and follow-up surveys and had blood work obtained approximately 8 weeks following completion of the initial vaccination series and 6 weeks following administration of an additional vaccine dose. We performed quantitative measurement of anti-receptor binding domain (RBD) IgG antibodies specific to SARS-CoV-2 using the LabCorp Cov2Quant IgG™ assay.

Results

A total of 659 participants were included [415 participants (63%) initially received BNT162b2, 243 participants (37%) initially received mRNA-1273, and 5 participants (1%) initially received Ad26.COV2.S]. Demographic, clinical, and treatment characteristics of the study population are provided in Table 1. Over 98% of those receiving an initial mRNA vaccine received the same type additional dose. Whereas 93% had detectable antibody after the initial vaccination series, 99.5% had detectable antibodies following an additional dose. Mean (SD) increase in antibody level was 61 ug/mL (103) in those receiving BNT162b2 and 78 ug/mL (143) for those receiving mRNA-1273 (Figure 1). Importantly, of 47 of patients without initial antibody response, 45 (96%) had detectable antibodies following an additional dose. Additional vaccination was generally well tolerated in this population, with 44%, 24%, 25%, and 6% reporting no, mild, moderate, and severe side effects respectively.

Conclusion

These findings demonstrate robust immunogenicity to additional doses of SARS-CoV-2 vaccine, even amongst patients with undetectable antibody following the initial series. Adverse event rates were low. These data can be used to inform vaccine decisions in patients with a broad array of immune-medicated conditions frequently managed by immunosuppression.
P691 Influence of ethnicity on the phenotype and clinical outcomes in Inflammatory Bowel Disease; comparison of a South American with a North American population
Authors: Pérez T , Pizarro B , Ascui G , Tobar F , Cerda-Villablanca M , Alvares D , Orellana M , De la Vega A , Canistra M , Cornejo B , Baez P , Silva V , Arriagada E , Estela R , Hernandez-Rocha C , Alvarez-Lobos M , Rivera-Nieves J
Published: January 2022

Background

Inflammatory Bowel Diseases (IBD) are chronic systemic inflammatory disorders, which affect the gastrointestinal tract. An increased incidence of IBD has been vastly reported in Europe, and North America, however, IBD has now emerged as a global disease affecting people of different genetic backgrounds and geographic locations, with increasing incidence in developing and newly industrialized regions such as South America, offering the opportunity to explore differences and similarities in disease presentation and outcomes across these variables.

Methods

Our study includes 265 patients with a diagnosis of Ulcerative Colitis (UC) (n=173) or Crohn′s Disease (CD) (n=92). We carried out an exploratory analysis of databases of Chilean and North American IBD patients to compare the clinical phenotype between both cohorts. We used an unsupervised machine learning approach using Principal Component Analysis (PCA), t- Stochastic Neighbor Embedding (t-SNE), among others, for each disease (CD and UC). Finally, we predicted the center (North American versus Chilean) using random forest, among other supervised machine learning methods to confirm these results.

Results

Several unsupervised machine learning methods separated two main groups supporting differences between North American and Chilean patients in each disease. The variables that explained the loadings of the clinical metadata on the principal components were related to therapies and disease extension/location at diagnose. Our Random Forest (RF) models were trained for cohort classification (Chilean or North American) based on clinical characteristics, obtaining a high accuracy of 0.86 (UC) and 0.89 (CD). Similarly, variables related to therapies and disease extension/location had a higher Gini index. In the same line, univariate analysis showed a later CD age at diagnoses in Chilean IBD patients (37 vs 24; p=0.005)

Conclusion

Our study suggests a clinical difference between North American and Chilean IBD patients; later CD age at diagnoses with a predominate less aggressive phenotype (39% vs. 54% B1), a more localized disease despite less biological therapies used in Chile for both diseases. The next research steps to confirm these results with more patients and explore more factors between different populations that could determine a less aggressive phenotype. Understanding the causes of these differences could unravel new pathways or protective factors, which could improve treatments.
P692 Clinical, therapeutic and evolutionary profile of fistulizing ano-perineal lesions in Crohn’s disease
Authors: Hassine H , Kahlaoui F , Mtir M , Cherif D , Tlili R , Kchir H , Maamouri N
Published: January 2022

Background

Ano-perineal lesions (APLs) during Crohn’s disease (CD) are frequent and varied. Ano-perineal fistulas (APF) are the most common and severe manifestations. They are associated with increased morbidity and considerable impairment of quality of life. Their management is not always easy despite therapeutic advances, particularly anti-TNFα.The aim of our work was to describe the epidemiological profile, the therapeutic modalities and the evolutionary aspects of APF during CD.

Methods

This was a retrospective, descriptive, single-center study collecting records of patients followed for CD with APF between January 2010 and December 2020. The patients had a proctological examination and a perineal MRI. We recorded clinical, endoscopic, radiological data, therapeutic management and clinical response to the initial therapeutic regimen. Complete remission was defined as closure of all initially productive fistulas, partial response was defined as closure of more than 50% of fistulas. Therapeutic failure was defined as closure of less than 50% of the initially productive fistulas.

Results

83 patients followed up for CD with APLs were collated of which 38 had APF (45.7%). The mean age was 42 years [26 - 73] with a sex ratio of 0.4. Active smoking was noted in six patients (15.8%). In 55.3% of cases, PAF was present at the time of diagnosis of CD (n=21).17 patients had developed one or more PAFs during the course of their disease with a mean delay of seven years [1 - 29]. APFs were associated with luminal involvement in 94.7% of cases, with ileal location in 10 patients (26.3%), colonic location in 13 patients (34.2%) and ileocolic location in 13 patients. The APFs were perianal in 34cases, vulvovaginal in five cases and gluteal in one case. There were complex fistulas in 92.1% of cases. The number of external orifices at the time of diagnosis was respectively: 1 orifice in 63.2% of cases, 2orifices in 26.3% of cases and more than two orifices in 10.5% of cases. A perineal abscess was associated in 44.7% of cases and anorectal stricture was observed in 7.9% of patients. Seton drainage was performed in 86.6% of patients. All patients with complex APF had received anti-TNFα after disappearance of collections if initially present (infliximab (92.1%), adalimumab (7.9%)) combined with thiopurines in 97.4% of cases. After a mean follow-up of 40 months, a complete remission was observed in 14 patients (36.8%), a partial response was noted in 13 patients (34.2%). 11 patients (28.9%) were in therapeutic failure.

Conclusion

In our study, APFs during CD account for almost half of all APLs.Thus, the development of local therapeutic means proves to be of necessity in order to increase the efficacy of biotherapies and to accelerate the healing of APFs.
P696 Genetic predisposition to infliximab immunogenicity in patients with immune-mediated inflammatory diseases – secondary analyses from a randomised clinical trial
Authors: Bjørlykke K , Brun M K , Viken M K , Stenvik G E , Klaasen R A , Gehin J E , Warren D J , Sexton J , Haavardsholm E A , Jahnsen J , Lie B A , Goll G L , Bolstad N , Syversen S W , Jørgensen K K
Published: January 2022

Background

Immunogenicity is a leading cause of treatment failure to TNF inhibitors. Genetic variations in HLA class II genes have been suggested to predispose to anti-drug antibody formation, but studies using high-resolution HLA typing as well as characterisation of biologically relevant haplotypes are currently lacking. The aim of this study was to assess associations between HLA loci and immunogenicity to infliximab.

Methods

Patients with immune-mediated inflammatory diseases (IMID) treated with infliximab (N=612) (120 rheumatoid arthritis, 181 spondyloarthritis, 72 psoriatic arthritis, 114 ulcerative colitis, 80 Crohn disease, and 45 psoriasis) were included in the randomised, Norwegian Drug Monitoring (NOR-DRUM) trial. Neutralising anti-drug antibodies were detected with an automated fluorescence assay. Next generation HLA sequencing at G group resolution were performed and trimmed to 2nd field. Haplotype analyses including the most significant HLA loci were performed, and epitope predictions for the infliximab light- and heavy-chain were assessed.

Results

Anti-drug antibodies to infliximab were detected in 147 (24 %) of patients. The most significant associations with immunogenicity were with the genes HLA-DQB1 (P=1.4x10-6), -DRB1 (P= 2.7x10-5), -DQA1 (P=0.00017) and -B (P=0.0009). Conditional analyses indicated that HLA-DQB1 represents the primary association(Table 1). Haplotype analyses showed that there was significantly increased risk of immnogenicity in patients carrying the HLA-DQ2 haplotypes DQB1*02:01~DQA1*05:01 (P=1.1x10-6) and DQB1*02:02~DQA1*02:01 (P=0.008), while one protective haplotype DQB1*05:01~DQA1*01:01 (P=0.0005) was identified (Figure 1a-c). Presence of HLA-DQ2 more than doubled the risk of anti-drug antibody formation (HR 2.54, 95%CI 1.82–3.56) (Figure 1d), in a model including the covariates age, sex, diagnosis, and concomitant immunosuppressive therapy. Association tests of each level of HLA analyses showed that HLA-DQ2 represents the strongest association(Figure 2). Epitope predictions revealed that the HLA-DQ2 haplotypes DQB1*02:01-DQA1*05:01 and DQB1*02:02-DQA1*02:01 share nine strong binder peptides, originating from the infliximab light chain, encompassing the amino acid core-peptide sequences INTVESEDI and VYACEVTHQ.

Conclusion

Using high-resolution HLA sequencing, we here demonstrate a genetic association between HLA-DQ2 and infliximab immunogenicity in IMID patients. The presence of either HLA-DQ2 risk haplotypes more than doubled the risk of anti-drug antibody formation across all diagnoses. Testing for HLA-DQ2 could be of clinical value in identifying patients at risk for immunogenicity and facilitate treatment decisions. Whether these findings apply to other TNF inhibitors should be further explored.