bluuebunny/crossref_metadata_2025 huggingface dataset:
P345 Lack of anti-TNF drugs levels in fistula tissue: A reason for non-response in Crohn’s perianal fistula?
Authors: Adegbola S , Sarafian M , Sahnan K , Pechlivanis A , Phillips R , Knowles C , Haddow J , Warusavitarne J , Faiz O , Tozer P , Holmes E , Hart A
Published: January 2020

Background

Anti-TNF therapy is recommended as a treatment for patients with Crohn ́s perianal fistulas. However, a significant proportion of patients have a sub-optimal response to anti-TNF therapy. Higher serum levels of anti-TNF agents have been associated with improved outcomes in perianal Crohn’s disease. Currently, it is unknown whether anti-TNF agent levels can be detected in tissue from fistula tracts themselves and whether this is associated with response.

Methods

We undertook a pilot study to develop a method to measure fistula tissue levels of anti-TNF medication (infliximab and adalimumab) using a targeted proteomic technique that employs ‘signature peptide detection’ following trypsin digestion called ultraperformance liquid chromatography–mass spectrometry (UPLC-MS), to quantify a protein. The targeted UPLC- MS/MS detection and quantification method implemented were previously validated. Biopsies were obtained from patients with Crohn’s disease who underwent an examination under anaesthesia for worsening fistula symptoms despite maintenance anti-TNF therapy. Idiopathic (cryptoglandular) tissues from purposively sampled matched (age/gender) patients were analysed as negative controls and these samples were spiked with anti-TNF drugs as positive controls.

Results

Tissue was sampled from the fistula tracts of seven patients with Crohn’s perianal disease (5 patients were on adalimumab and 2 patients were on infliximab). The limit of detection (LOD) and linearity range of the method was assessed for each drug in the spiked idiopathic fistula samples. Infliximab and adalimumab had a LOD of 0.004 and 2 μg/ml respectively with linearity demonstrated for both drugs. The anti-TNF drugs, infliximab and adalimumab, were not detected in fistula samples from any of the Crohn’s patients despite detection in ‘spiked’ positive control samples. In addition, to validate the result, samples were concentrated (x10) and still there was no detection of the drugs in the test samples.

Conclusion

The anti-TNF drugs adalimumab and infliximab were not detected in fistula biopsy samples from patients with Crohn ́s perianal fistulas with refractory symptoms despite maintenance therapy. This raises the question on the role of tissue penetrance of anti-TNF drugs in response to therapy. Further work is required in a larger number of patients to validate the findings observed and investigate whether any correlation exists between tissue and serum levels of anti-TNF and clinical outcome.
P349 Infliximab in inflammatory bowel disease: Is premedication necessary?
Authors: Núñez P , Figueroa C , Flores L , Ibáñez P , Kronberg U , Lubascher J , Pizarro G , Quera R , Simian D
Published: January 2020

Background

The use of infliximab (IFX) in inflammatory bowel disease (IBD) has been associated with a 1–6% risk of infusion reactions. The usefulness of premedication with corticosteroids, paracetamol and/or antihistamines is controversial. The aim of this study is to assess, in IBD patients on IFX, whether there are differences in secondary reactions to the infusion between those who use premedication or not.

Methods

A retrospective cohort study was performed identifying patients with a diagnosis of IBD who received IFX at a tertiary centre in Santiago-Chile, since 2009. Acute reactions were defined as those that occurred in the first 24 h post-infusion and late reactions for more than 24 h. Infusion reactions were classified as mild, moderate and severe. Descriptive and association statistics were used (χ 2; p < 0.05).

Results

Sixty-four patients were included with 1,263 infusions in total, 52% men (characteristics in Table 1). Median infusions per patient were 22 (2–66). All induction infusions were administered with premedication and in maintenance, 57% of them. Premedication was given with hydrocortisone, chlorphenamine and paracetamol. Flow chart according to premedication use or not is shown in Figure 1. In the maintenance group, there were 10/718 (1.4%) infusion reactions with premedication and 3/358 (0.8%) without it, non-significant differences (p = 0.432). In the induction group, there were 8/187 (4%) infusion reactions, significantly higher when compared with both maintenance groups (Figure 2).

Conclusion

In this cohort, premedication use in maintenance phase was not effective at reducing the rate of infusion reactions due to IFX. These results suggest that premedication would not be necessary during maintenance.
P353 Assessing compliance to screening for infectious diseases and vaccination in patients newly diagnosed with inflammatory bowel disease
Authors: Pringle R , Assadsangabi A
Published: January 2020

Background

Patients are frequently counselled on vaccinations and screened for infectious diseases prior to starting immune-modulating therapy; however, the most up-to-date ECCO guideline on the subject (1) recommends vaccination screening and completion at diagnosis. We assessed adherence to the ECCO guidelines in patients diagnosed with inflammatory bowel disease (IBD).

Methods

Medical records from 100 IBD patients up to 6 months of their diagnosis were analysed retrospectively at a tertiary IBD centre in the UK. Data were collected for infectious diseases screening, documentation of vaccination history and education/advice on vaccination. Vaccination rates for diphtheria, tetanus, pertussis, polio, hepatitis B, human papillomavirus (HPV), influenza, pneumococcal and varicella-zoster were documented if they were recorded in the medical notes.

Results

A total of 84% of patients were not screened for infectious diseases at diagnosis or within 6 months. Overall, 97% had no vaccination history documented and 97% were not advised to attend their GPs for vaccinations.

Conclusion

Despite the existence of international guidelines, poor compliance to vaccination in patients with IBD has been shown in line with previous reports (2). This suboptimal vaccination compliance could be partly due to poor documentation and the retrospective method of data collection. However, there is clearly an urgent need for education and execution of vaccination guidelines in IBD. This implementation of work is now ongoing at our unit through automatic formal standard vaccination notification on every IBD clinic visit, which will be further re-audited in 6 months’ time.
P364 New insights into the molecular mechanisms of thalidomide in paediatric inflammatory bowel disease patients
Authors: Lucafò M , Bramuzzo M , Pugnetti L , Gerdol M , Greco S , Paci M , Curci D , Nonnis M , Renzo S , Lionetti P , Tommasini A , Decorti G , Stocco G
Published: January 2020

Background

Thalidomide is an effective drug in children with inflammatory bowel disease (IBD) refractory to standard treatments, however, its use is often limited by its safety profile, in particular for the risk of teratogenicity and peripheral neuropathy. Multiple hypotheses exist to explain the molecular mechanism of thalidomide action but no data have been published on IBD patients. To identify determinants of thalidomide action in paediatric IBD, high-throughput microRNA (miRNA) and messenger RNAs (mRNA) profiles during treatment were analysed.

Methods

IBD patients responsive to thalidomide were enrolled. miRNA and mRNA profiles from peripheral blood obtained before and after 12 weeks of treatment were determined using next-generation sequencing. Differentially expressed genes were identified by fold change from the general linear model. In order to detect the potentially altered pathways, the hypergeometric test based on gene ontology annotations was used. The identification of putative mRNA targets of thalidomide sensitive miRNAs was performed by Targetscan database.

Results

Ten IBD paediatric patients (mean age 13.1 years, 6 males) were enrolled. Sequencing analysis identified 10 miRNAs (3 downregulated) and 252 mRNAs (76 downregulated) deregulated after treatment. Five upregulated miRNAs could putatively recognise the 3′UTR of several Hox genes, a group of transcription factors that play important roles in the development of structures such as limbs, lungs and nervous system. The hypergeometric test highlighted the altered pathways involved in inflammatory response, regulation of immune system, prostaglandin receptor activity and G protein-coupled receptor signalling. Among the 10 miRNAs deregulated by thalidomide, six could putatively regulate the differentially expressed mRNAs resulting from the analyses.

Conclusion

Thalidomide induces specific gene expression alterations, which could help to elucidate its molecular mechanism in paediatric IBD patients. miRNA results may suggest new molecular targets involved in the teratogenic effects of this drug. Moreover, mRNA profiles indicate a strong involvement of adenylate cyclase-modulating G protein-coupled receptor signalling in the thalidomide mechanism of action.
P365 Identification of predictive factors of AZA/6-MP treatment outcome in paediatric luminal Crohn’s disease: a multicentre study of the paediatric IBD Porto group of ESPGHAN
Authors: LERCHOVA T , Hradsky O , Kulich M , Veres G , Dias J A , Sladek M , Kolacek S , Van Biervliet S , Melek J , Serban D , Winther K , de Meij T , Schwarz J , Kolho K L , Escher J C , Bronsky J
Published: January 2020

Background

According to current guidelines, most paediatric patients in Europe diagnosed with Crohn′s disease (CD) are prescribed long-term immunosuppressive therapy with azathioprine (AZA). This study aimed to develop a predictive model allowing to stratify patients who will not benefit from AZA maintenance treatment and who require a more intensive therapeutic approach early after diagnosis.

Methods

The study was designed to develop a clinical prediction rule using retrospective data analysis from patients included to prospective inception cohort, the EUROKIDS-IBD until 2017. In total, 1190 CD patients using AZA were selected from the registry in 13 European centres. Of these, 441 patients who responded to induction treatment, started AZA treatment within 6 weeks from the time of diagnosis and maintained remission at week 12 were entered into this multicentre study. The primary outcome was time to clinical relapse defined as a necessity of re-induction of remission. A sequence of Cox models was fitted to predict the risk of relapse. Variables appearing to be significant in univariate risk analyses were added to the model one by one and non-significant terms were dropped.

Results

More than 50 % of patients did not experience a clinical relapse within 2 years of AZA treatment (Figure 1). The median time to relapse was 2.11 (CI 1.59–2.46) years. Out of all tested parameters available at the time of diagnosis,8 were predictive in the context of early relapse. Only 4 of these variables, namely centre (p = 0.0009), age (HR = 1.389 95% CI (1.004–1.921), p = 0.047), CRP (HR = 1.504 95% CI (1.116–2.027), p = 0.008) and BMI Z-score (HR = 0.830 95% CI (0.742–0.928), p = 0.001), remained significant in multivariate analyses.

Conclusion

In paediatric CD patients achieving clinical remission after induction treatment at week 12, AZA was effective as maintenance treatment in over 50% of patients for 2 years. Due to low values of HR, the possibility to predict relapse on AZA treatment appears to be limited.

Acknowledgement: This work was supported by the Grant Agency of Charles University in Prague [grant number 364617] and by Ministry of Health, Czech Republic-conceptual development of research organisation, Motol University Hospital, Prague, Czech Republic [00064203].
P376 Real life health care utilisation in paediatric patients with inflammatory bowel disease in the era of biologics
Authors: Tchogna S A , Yang X Y , Deslandres C , Jantchou P
Published: January 2020

Background

The burden associated with the management of paediatric patients with inflammatory bowel disease (IBD) has been rising as the incidence of IBD is increasing in children. In addition, the widespread use of biologics and a treat-to-target approach also contributes to the increase of healthcare utilisation.

Methods

The purpose of this study was to assess the health care services utilisation and the associated factors in a prospective cohort of children diagnosed with IBD in Quebec, Canada. Patients diagnosed from 2013 to 2015 and followed up until the transfer to adult care were identified in our IBD database. Data on IBD related services and treatments: imaging procedures, hospitalisations and outpatient visits, medications from diagnosis to transition was extracted. We analyzed the healthcare utilisation according to the baseline disease severity (paediatric Crohn’s disease activity index or paediatric ulcerative colitis activity index) at diagnosis, and according to exposition to intravenous biologics.

Results

In total, 144 patients were included in the study [(77 males), CD (N = 98), UC (N = 31) and IBD-U (N = 15); median (interquartile(IQR)) age at diagnosis 15.2 (14.3–16.3) years]. The median (IQR) duration of paediatric follow-up was 2.9 (1.8–3.9) years. The median (min-max) number of imaging procedures varied largely: esophagogastroduodenoscopy 1(0–2), colonoscopy 1(1–6), abdominal ultrasound1(0–13), abdominal MRI 1(0–4), tomodensitometry 0(0–2), bone densitometry 1(0–5). Patients had various follow-up encounters (median(min–max)): outpatient visits 9(1–28), IBD nurses phone follow-ups 4(0–33). Sixty-four per cent of patients had at least one hospitalisation [median(min–max)1(0–10); median duration 4(0–150 days)] and 35.41% had at least one emergency visit. Baseline disease severity did not predict the disease burden: the mean number of encounters was 3.0/year in the moderate/severe group as compared with 2.5/year in the mild group; p = 0.61. Among the, 63.5% of patients exposed to an intravenous biologic (Infliximab or Vedolizumab), those exposed earlier (<3 months after diagnosis) used more health care services (mean = 3.3/year) than those exposed later (mean = 2.23/year); p <0.0001. In addition, the median (IQR) cumulative days of healthcare utilisation (missing school days) for patients treated with intravenous biologics was 48.5(32.4–67.9) days during paediatric care.

Conclusion

Adolescents with IBD have several healthcare encounters between the diagnosis and transfer to adult care. Disease severity at diagnosis was not related to a higher level of health services utilisation during follow-up. However, treatment with intravenous biologics was associated with a high health service utilisation and school missing during follow-up.
P383 The level of intestinal inflammation and fibrosis in resection specimens after preoperative anti-tumour necrosis factor-α treatment in patients with Crohn’s disease: a comparative pilot study
Authors: Torle J , Dabir P , Korsgaard U , Christiansen J J , Qvist N , El-Hussuna A
Published: January 2020

Background

Strictures are a common complication in Crohn’s disease (CD), which are found in more than 50% of the patients. They are characterised by excessive deposition of extracellular proteins in the tissue as a result of the chronic inflammatory process. The effect of anti- TNF-α therapy on the development of fibrosis is not yet fully understood. The aim of the study was to investigate whether the degree of intestinal inflammation and fibrosis correlates with pre-operative anti-TNF-α therapy in patients with Crohn’s disease undergoing bowel resection.

Methods

This is an unblinded, prospective, multicentre cohort pilot study. All adult patients with Crohn’s disease, who underwent elective, laparoscopic or open intestinal resection were included. Pre-operative blood investigations included measurement of TNF- α concentration and specific drug antibodies in addition to the concentration of selected inflammatory cytokines. Three pathologists examined the specimens independently and assessed the degree of inflammation and fibrosis.

Results

Histopathological specimens from 10 patients with CD who underwent ileocecal or ileocolic resections were retrieved. Four of those patients were on anti-TNF-α treatment pre-operatively. The last dose of anti-TNF-α agents was administered within 1–9 weeks prior to bowel resection. Patients on anti-TNF-α treatment had higher fibrosis score than the controls (p = 0.01). Anti-TNF-α treatment was not associated with an increase in either CD68 or CD163-positive macrophages. There was no significant relationship between time from last anti-TNF-α dose to surgery, and fibrosis score. No significant association between the concentration of major inflammatory cytokines including TNF-α and fibrosis score or degree of inflammation was found.

Conclusion

Patients on anti-TNF-α treatment had higher fibrosis score than the controls.
P389 Post induction infliximab trough levels predict long-term endoscopic remission in paediatric patients with inflammatory bowel disease
Authors: van Hoeve K , Dreesen E , Hoffman I , Ferrante M , Vermeire S
Published: January 2020

Background

Although higher infliximab (IFX) trough levels (TL) have been associated with better outcomes, the ideal predictive sampling time and cut-points to achieve endoscopic remission remain unclear in children with inflammatory bowel disease (IBD). Therefore, we evaluated the pharmacokinetics of IFX during induction to predict long-term outcome of IFX.

Methods

All children with Crohn’s disease (CD) or ulcerative colitis (UC) starting IFX therapy (5 mg/kg at weeks 0–2–6–12) for active luminal disease from May 2017 till May 2019 were followed prospectively. IFX levels were measured by Ridascreen IFX Monitoring ELISA (TL at weeks 2–6–12, peak at weeks 0–2–6 and intermediate at weeks 1–4). IFX levels and cumulative drug exposure (area under the curve (AUC) till week 12) were correlated with the outcome at month 6. Clinical remission was defined as PUCAI/PCDAI <10, biochemical remission as CRP ≤5 mg/l + ESR ≤20 mm/h, endoscopic remission as SES-CD <3 or Mayo endoscopic sub-score = 0 and deep remission if both clinical + endoscopic remission. Results were analysed using Mann–Whitney U-test (presented as median [IQR]).

Results

A total of 252 serum induction levels were included from 32 patients (20 CD and 12 UC; 38% male; median age at start of IFX 13.8 years [11.3–14.9]; 84% on concomitant thiopurines). Clinical remission was achieved in 24 (75%) patients and 18 (56%) were in endoscopic remission (all in deep remission) at month 6. Endoscopic remission at month 6 was associated with significantly higher median IFX TL at week 4 (38.8 µg/ml [24.3–46.0] vs. 23.5 µg/ml [10.5–36.6], p = 0.017), at week 6 (19.9 µg/ml [10.1–26.3] vs. 11.1 µg/ml [3.7–19.9], p = 0.031), at week 12 (9.6 µg/ml [5.5–11.9] vs. 3.5 µg/ml [2.7–7.2], p = 0.004; fig1.) and higher AUC week 0–12 (4574.7 µg*day/ml [3783.0–5160.8] vs. 3722.9 µg*day/ml [3102.2–3991.9], p = 0.008). Median IFX TL at week 12 were significantly higher in children with clinical remission (8.6 µg/ml [5.1–12.0] vs. 4.3 µg/ml [3.1–5.9], p = 0.033), but not for biological remission (6.7 µg/ml [4.0–12.0] vs. 4.3 µg/ml [1.2–7.2], p = 0.250; Figure 2) at month 6. ROC analysis identified an IFX TL at week 12 ≥ 5.0 µg/ml and an AUC weeks 0–12 ≥ 4056.0 µg*day/ml as minimal target to achieve endoscopic remission at mo. 6 (AUROC: 0.796 [95% CI: 0.62–0.97] and AUROC: 0.778 [95% CI: 0.61–0.94], respectively; Figure 3.). Height, haemoglobin and PCDAI score at start of IFX therapy, significantly correlated with week 12 IFX TL.

Conclusion

Adequate IFX exposure during induction in paediatric IBD patients is associated with significantly better clinical, endoscopic and deep remission rates at month 6. Model-informed precision dosing can assist physicians to achieve optimal exposure during induction more precisely (and rapidly) what is essential for an optimal outcome.
P394 Preoperative factors associated with prolonged postoperative in-hospital length of stay in patients with Crohn’s disease undergoing intestinal resection or strictureplasty
Authors: Vinh Luong T , Dich Grandt S , Negoi I , Palubinskas S , El-Hussuna A
Published: January 2020

Background

Postoperative complications might not be accurately registered, leading to weakness in registry data studies.

Aim

To investigate factors that influence postoperative in-hospital length of stay (LOS) in patients with Crohn’s disease (CD) undergoing bowel surgery. Furthermore, the study aimed to evaluate LOS as a surrogate for postoperative outcome.

Methods

A multicentre retrospective cohort study. Inclusion criteria were adult patients with CD who underwent bowel surgery with either anastomosis or stricturoplasty. All timings of surgeries are regardless of the method of access to the abdominal cavities. Patients with stoma were excluded. Demographic data, preoperative medications, previous operations for CD, preoperative sepsis, and operation was recorded. The primary outcome was LOS while the secondary outcome variable was postoperative complications.

Results

449 patients who underwent abdominal surgery for CD were included. 265/449 (59%) were female. Median age was 37 years (IQR =20), median LOS was seven days (IQR =6). Patients with longer LOS had higher rates of re-laparotomy/re-laparoscopy (45/228 (19.7%) vs. 9/219 (4.1%) p = 0.01). In multivariate analysis, age (OR = 1.024 [CI 95% 1.007–1.041], p = 0.005), preoperative intra-abdominal abscess (OR =0.39 [CI 95% 0.185–0.821], p = 0.013), and previous laparotomy/laparoscopy (Or = 0.57 [CI 95% 0.334–0.918], p = 0.021) were associated with prolonged LOS. LOS correlated with postoperative complications after adjustment for age, gender, previous laparotomy/laparoscopy, and preoperative intra-abdominal abscesses (OR = 1.28 [CI 95% 1.199–1.366], p < 0.0001).

Conclusion

Age, preoperative intra-abdominal abscess, and previous laparotomy/laparoscopy significantly prolonged LOS. LOS correlated with postoperative complications and can, therefore, act as a surrogate for the postoperative outcome.
P395 Management of pouch vaginal fistulae in ulcerative colitis: A 35-year experience
Authors: REZA L , Van Praag E , Iqbal N , Twum-Barima C , Hart A , Clark S , Tozer P
Published: January 2020

Background

Pouch vaginal fistulae (PVF) occur following restorative proctocolectomy with an incidence of 6%. The overall rate of pouch failure is 10% but may be as high as 29% with a PVF. PVF can be relatively asymptomatic, with low volume vaginal mucus discharge alone, or can cause considerable morbidity with persistent, passive leakage of faeces and gross perianal excoriation. Management is challenging with a range of reparative techniques reported and no gold standard. Despite a lack of evidence, anti-TNF agents are increasingly used. It is unclear whether there are factors which may predict fistula closure with anti-TNF therapy. The primary aim of fistula therapy should be fistula eradication or amelioration of fistula symptoms without worsening pouch function.

Methods

This is a retrospective analysis of the management of PVF in ulcerative colitis in a tertiary referral centre. Demographic, clinical history and presenting symptoms of fistula including pouch function were collected. Symptomatic burden related to the fistula and the presence or absence of gastrointestinal continuity were assessed.

Results

Fifty patients with PVF were identified between 1984 and 2019 and complete clinical notes were available and analysed for 30 of these. The median age at diagnosis was 36 (range 19–52) years. The median follow-up from pouch creation was 12.5 years. A PVF developed in 30% within 1 year of pouch creation and in 70% after 1 year. In this cohort, 17 (56%) maintained gastrointestinal continuity, of whom 13 were asymptomatic of fistula symptoms (11 after intervention), while 4 were symptomatic but declined intervention. Of the 11 patients who were asymptomatic following treatment, 3 had perianal pouch advancement, 1 had a redo transabdominal pouch, 2 had transvaginal repair, 2 had seton drainage and 3 patients were managed with anti-TNF therapy. Anti-TNF agents were used in 5 patients, 1 of whom was already defunctioned. Three achieved quiescence of symptoms, with 1 requiring pouch excision due to ongoing symptoms. Three patients with poor pouch function prior to anti-TNF therapy noted an improvement in pouch function. Pouch excision or permanent defunctioning was performed in 13 patients (predominantly due to the burden of fistula symptoms rather than poor pouch function).

Conclusion

Around 50% of patients with PVF required pouch excision or permanent defunctioning. The burden of fistula symptoms drove this decision, rather than overall poor pouch function. Anti- TNF therapy improved pouch function and fistula symptoms in a small group of patients but the evidence supporting its use and indications remain limited.
P397 Surveillance in ulcerative colitis: Can we predict the risk for intraepithelial neoplasia?
Authors: Estorninho J , Freire P , Lopes S , Ferreira M , Ferreira M , Portela F , Figueiredo P
Published: January 2020

Background

Ulcerative colitis (UC) has been associated with an increased risk of colorectal cancer (CRC). Although dye spray chromoendoscopy showed superiority to standard colonoscopy in surveillance studies, with the availability of higher-resolution colonoscopes, the utility of chromoendoscopy (CE) has been questioned. We aimed to evaluate the risk of intraepithelial neoplasia (IN) after a high-quality screening colonoscopy (making use of CE or random biopsies (RB) and removing all detected lesions) in a population with longstanding UC and to identify potential risk factors for dysplasia incidence.

Methods

In a previous study, 145 patients with clinically and endoscopic longstanding (≥8 yr) distal/extensive UC without primary sclerosing cholangitis and/or history of IN were prospectively randomised to undergo CE or RB. In this study, after a median follow-up of 5 additional years, we evaluated subsequent IN incidence in these patients, submitted to surveillance colonoscopy. Patients without high-quality surveillance colonoscopy (with good bowel preparation and cecum intubation) using high-definition were excluded.

Results

One hundred and twenty-one patients were included. Nine had removed adenomas with low-grade dysplasia in the index colonoscopy. Now, in surveillance colonoscopy, we detected 9 (7.4%) IN: low-grade dysplasia was found in 8 (6.6%) patients and a colorectal adenocarcinoma in 1 (0.008%) patient. After multivariate analysis, IN was significantly associated with older age (68 vs. 52 years, p < 0.05) and higher disease duration (26 vs. 20 years, p < 0.05). No association was found between IN and previous detection of IN in screening colonoscopy sex, the CE or RB use in index colonoscopy, extent of disease, The presence of pseudopolyps, smoking habits, familial history of CRC or maintenance therapy for UC.

Conclusion

In this study, older patients and higher disease duration were associated with a higher risk of IN in surveillance colonoscopy.
P400 Understanding the impact of TNF-α antagonists on the severity of non-melanoma skin cancer in inflammatory bowel disease and the consequences for therapy
Authors: Townsend C , Khanna R , Wilson A S
Published: January 2020

Background

Non-melanoma skin cancer (NMSC) accounts for at least 40% of all new cancer diagnoses in Canada annually and presents a significant cost to the health care system due to the volume of cases. The incidence of NMSC in patients with inflammatory bowel disease (IBD) is higher when compared with the general population. Generally, in a non-IBD population, the risk of further NMSC progression is low; however, little data exists that highlights differences in the clinical course of patients diagnosed with NMSC who have IBD and are TNF-α antagonist exposed. It is unclear if TNF-α antagonist therapy should be discontinued in this patient population.

Our goal is to determine whether TNF-α antagonist exposure in IBD is associated with a high-risk NMSC presentation at diagnosis, as defined by the National Comprehensive Cancer Network (NCCN) stratification. Our secondary objectives include the presence of positive margins following resection, presence of metastatic disease on initial presentation, the requirement of additional therapy to treat NMSC, number of patients who had TNF-α antagonist therapy discontinued following the diagnosis of NMSC and number of individuals with recurrent NMSC.

Methods

Four hundred and twenty-four IBD patients seen at London Health Sciences Centre were reviewed. We have identified 22 patients who were diagnosed with NMSC. Twelve patients had a pre-NMSC TNF-α antagonist exposure while 10 patients who developed an NMSC and had no TNF-α antagonist exposure prior to NMSC diagnosis.

Results

Preliminary results of the primary outcome demonstrate that 50% (6/12) of patients who have been exposed to TNF antagonist therapy presented with a high-risk NMSC lesion at diagnosis compared with 40% (4/10) who were not exposed (OR 5.16, 95% CI 0.47–57.00; p = 0.181). Preliminary results of the secondary outcomes suggest that 25% (3/12) of patients exposed to TNF-α antagonist had positive margins compared with 0% (0/10) of patients who were not exposed. No patients in either group presented with metastatic disease. Twenty-five per cent (3/12) of patients in the exposed group received more advanced treatment compared with 0% (0/10) in the non-exposed group. Eight per cent (1/12) of patients in the TNF-α antagonist group had their IBD therapy changed from a TNF-α antagonist to an alternative biologic class, and 17% of patients (2/12) in the TNF-α antagonist group had recurrent NMSC lesions.

Conclusion

In conclusion, preliminary results suggest that TNF-α antagonist exposure may be associated with higher risk NMSC lesion at presentation. Further expansion of the sample size is required to explore these hypotheses further.
P404 Prolonged steroid exposure prior to admission is associated with increased likelihood of rescue therapy and colectomy in acute severe ulcerative colitis
Authors: Barnes A , Spizzo P
Published: January 2020

Background

Steroid exposure has been associated with poorer outcomes following colectomy in acute severe ulcerative colitis. Current treatment algorithms suggest three days of high dose intravenous steroid before the decision to commence rescue therapy. We aimed to look at medium-term outcomes in acute severe ulcerative colitis and their predictors including steroid exposure prior to admission.

Methods

A retrospective case note and electronic record review were conducted at a tertiary inflammatory bowel disease referral centre of admissions for acute severe ulcerative colitis meeting Truelove and Witts criteria from 2013 to 2019. Identified admissions were categorised as: not on steroid prior to admission or on steroid for less than one week prior to admission, on steroid for over one week prior to admission, and on steroid for over one month prior to admission. Data were analysed using Chi-squared test and Fisher’s exact test as appropriate.

Results

In total, 109 admissions were identified for acute severe ulcerative colitis meeting Truelove and Witts criteria over 2013 to 2019. Rescue therapy was significantly more likely in patients with over one week of steroid exposure prior to admission (76.0% vs. 28.5%, p = 0.0001). Prior steroid exposure was not associated with failure of medical rescue therapy (p = 0.42). Patients with steroid exposure for at least one week prior to admission trended towards increased likelihood to undergo colectomy during admission (32.0% vs. 16.6%, p = 0.0.09) and were significantly more likely to undergo colectomy within one year of admission (44.0% vs. 21.4%, p = 0.028).

Excluding patients with a first presentation of inflammatory bowel disease showed that patients with steroid exposure for at least one week prior to admission trended towards significance to undergo colectomy during admission (32.0% vs. 13.2%, p = 0.05) and were significantly more likely to undergo colectomy within one year of admission (44.0% vs. 20.7%, p = 0.036). Readmissions within one year of acute severe ulcerative colitis admission were not significantly different (40.0% vs. 29.7%, p = 0.33).

Conclusion

Prolonged steroid exposure prior to admission was associated with an increased likelihood of rescue therapy but was not predictive of response to medical rescue therapy. Colectomy rates at one year were significantly higher with over one week of steroid exposure prior to admission. Consideration should be given to early commencement of rescue therapy in those with prolonged steroid exposure prior to admission.
P406 Adherence, acceptability and serum trough concentration of adalimumab autoinjector in quiescent patients with inflammatory bowel diseases
Authors: Kato S , Yamaga N , Ishibashi A , Kani K , Nagoshi S
Published: January 2020

Background

Anti-TNF α antibodies have contributed to the good prognosis in patients with inflammatory bowel diseases (IBDs). Adherence of these drugs affects the treatment effects in patients with IBDs. Recently, the use of an adalimumab (ADA) autoinjector (AI) was approved in Japan. However, the effects of the use of this AI in patients with IBDs are not clear. We elucidated whether the use of an AI for ADA administration improves the adherence to and acceptability of ADA therapy compared with the use of syringe (SYR) type.

Methods

This was a single-centre prospective observational study approved by the institutional review board of our hospital. Twenty-six quiescent IBD patients, including ulcerative colitis and Crohn’s disease, treated by administration of ADA 40 mg using SYR every other week for >6 months or naive to ADA were enrolled in this study. The patients administered treatment using SYR were switched to an AI. The AI-naive and AI-switched patients were administered ADA treatment using AI for 6 months. The levels of adherence and acceptability, including pain and satisfaction levels, were measured using the visual analogue scale before and after treatment with ADA administered using AI. Serum ADA trough levels were also examined.

Results

Of the 26 enrolled patients, 1 with selection error, 1 with a rejection of approval and 2 with recurrence were excluded. In total, 24 participants were included in the final analysis. The mean (SD) age of the participants was 12.6 (8.4) years. Of the participants, 54.5% (12/22) were male, 68.2% (15/22) had ulcerative colitis, 27.3% (6/22) used thiopurine and 77.35 (17/22) were administered treatment using SYR. The adherence rate improved after switching to AI. The adherence rate of patients who received maintenance ADA was not significantly different from that of the ADA-naive patients (SYR type: 89.1 ± 12.7 mm, AI-switch: 94.0 ± 8.6 mm, AI-naive: 87.0 ± 21.6 mm, not significant [NS]). According to the acceptability of ADA AI, the pain intensity significantly decreased after switching. It was also significantly lower in the AI-naive group than in the SYR group (SYR: 55.0 ± 24.8 mm, AI-switch*: 87.3 ± 15.4 mm, AI-naive*: 92.2 ± 10.1 mm, *p < 0.01 compared with SYR). The level of satisfaction significantly increased after switching (SYR: 62.6 ± 27.9 mm, AI-switch*: 85.9 ± 12.5 mm, AI-naive: 81.2 ± 20.9 mm; *p < 0.01, compared with SYR). The ADA trough level was not significantly different after switching (SYR: 11.0 ± 9.1 mg/ml, AI-switch: 9.9 ± 5.5 mg/ml, NS).

Conclusion

ADA administration using AI resulted in significantly improved acceptability without changes in serum ADA trough levels.
P407 Is the rapid infliximab infusion a safe and cost-saving strategy in paediatric inflammatory bowel disease?
Authors: Pujol Muncunill G , Martínez-Osorio J , Bossacoma-Busquets F , Álvarez-Carnero L , Arrojo-Juárez J , Vila-Miravet V , Martin De Carpi F J
Published: January 2020

Background

Rapid infliximab (IFX) infusion administered over 60 min is a safe strategy in selected Inflammatory Bowel Disease (IBD) adult patients. Some paediatric studies found similar results among children but data are still scarce. The aim of our study is to evaluate the safety of rapid IFX infusion strategy in our cohort of Paediatric IBD (PIBD) patients and analyze the impact of this strategy on health care resources.

Methods

Paediatric IBD patients under IFX treatment using standard protocol (2-h IFX infusion), and who had received at least 4 previous standard infusions, with no dose change in the last 2 doses, and without infusion reactions were switched to receive a 1-h IFX infusions. Demographic and clinical data were collected from medical records, and patient and family satisfaction was recorded by a telephone survey. The optimisation of health care resources was also analyzed.

Results

A total of 46 PIBD patients were under IFX treatment during the study period (February 2018-February 2019) of whom 26 met inclusion criteria and were switched to rapid IFX infusions (14 Crohn’s disease (CD), 12 ulcerative colitis; 17 males). The mean age at switch was 15.3 years (IQR 5.3–17.9) with a mean time of IFX use of 30 months (IQR: 4–78). Sixteen patients were receiving concomitant immunomodulators. A total of 154 rapid IFX infusions were administered with a mean dose of IFX of 5.4 mg/kg (IQR 4–10) and an average frequency of 6.7 weeks (IQR 4–8). No patient received premedication at any time and no infusion reactions were seen during the study period. Family and patient satisfaction (22/26) was higher in rapid IFX infusion strategy than in standard protocol (9.1/10 vs. 7.6/10). During the study period, 154 h of hospitalisation were saved.

Conclusion

Rapid IFX infusion strategy in selected PIBD patients is safe and well accepted by patients and their families. In addition, it is a cost-saving strategy, minimising the loss of work and teaching hours by the caregivers and patients, and allows optimisation of the hospital resources. These results have led us to establish rapid IFX infusion in selected patients (with stable previous doses and no infusion reactions) as the standard protocol in our centre.
P409 Endoscopic and histological activity is associated with non-response to biologic therapy in ulcerative colitis
Authors: WANN S , Norris R , Williams R , Basnayake C , Lust M , Wright E , Kamm M , Connell W , Thompson A , Ding N
Published: January 2020

Background

Ulcerative colitis (UC) is a chronic inflammatory bowel disease, characterised by a relapsing and remitting course. Biologic therapy in UC has a 30% rate of primary non-response (PNR) and a further 5% loss of response per year. Prognostic indicators of non-response include younger age and longer disease duration. Emerging evidence suggests that endoscopic and histological activity is associated with adverse outcomes such as clinical relapse and colectomy. However, the role of endoscopic or histological disease activity in predicting non-response to biologic therapy is unclear. We aim to investigate the association of endoscopic and histological activity with non-response to biologic therapy in UC.

Methods

Patients with UC treated with biologic therapy between 2014 and 2019 were studied. Baseline endoscopic disease activity was assessed using the Mayo endoscopic subscore from endoscopy performed prior to commencing biologic therapy. Patients who underwent colonoscopy 3–9 months after commencing biologic therapy were selected for histopathological review. Sigmoid biopsies were evaluated by an expert gastrointestinal pathologist. Histological parameters were scored on a 4-point scale, with blinding to clinical and endoscopic outcomes.

Results

Sixty-six patients were followed for a median of 16 months (IQR 6–30), 12 (18%) of whom did not respond to biologic therapy initially and 3 (6%) of whom lost response secondarily. Baseline endoscopic activity was associated with non-response (OR 6.1, 95% confidence interval 1.3 – 29.4, for every 1-point increase in the 4-point Mayo endoscopic subscore). 23 patients were identified for histopathological review. Four (17%) patients exhibited PNR. Baseline crypt atrophy was associated with PNR (p = 0.014) and baseline bifid crypts and crypt atrophy were associated with 52-week clinical relapse (p = 0.482 and p = 0.0497).

Conclusion

For patients with UC, endoscopic disease activity assessed prior to commencing biologic therapy has the potential to predict non-response to biologic therapy. In addition, specific histological parameters relating to crypt inflammation and crypt architecture may also predict non-response. Further prospective studies should be conducted to investigate the clinical utility of assessing endoscopic and histological disease activity prior to commencing biologic therapy.
P413 General impressions about nutrition in patients with inflammatory bowel disease using a nutritional survey
Authors: Ruiz-Ramirez M A , Suarez C , Poza J , Martin-Arranz E , Rueda-Garcia J L , Sanchez-Azofra M , Cuadros M , Mayor P , Garcia-Ramirez L , Martin-Arranz M D
Published: January 2020

Background

Malnutrition is a frequent problem in inflammatory bowel disease (IBD) due to the increase in caloric consumption because of the pathology itself and due to the reduced intake. This low intake is mainly caused by the symptoms and the anorexia associated with the disease, but it is more and more common for patients to adopt elimination diets. Our aim was to investigate the general ideas about nutrition in patients with IBD, as well as to determine whether they consider that health professionals value the nutritional aspect.

Methods

Inclusion of patients with an established diagnosis of IBD followed-up in the unit of the Hospital Universitario La Paz, using an anonymised survey for the researcher and for the attending physician.

Results

A total of 118 patients were included, of which 56% (65 patients) were women. The mean age of the patients was 48.84 years (SD 14.2). All patients had a previous diagnosis of IBD: 51.7% (61 patients) ulcerative colitis (UC), 45% (53 patients) Crohn’s disease (CD) and 3.3% (4 patients) undetermined colitis. 55.6% (64 patients) believed that nutrition influenced the course of their IBD. The patients who answered yes were on average younger (44.5 vs. 53.9 years), these differences being statistically significant (p = 0.0003). Only 22 of the 64 patients (34.4%) believed that it was caused by a specific food or food group and the most frequent answer was food rich in fats, dairy products, alcohol or spices. 52.1% of the sample (61 patients) had eliminated some food from the diet since the diagnosis of IBD. The most noteworthy was the avoiding of dairy products (37%), fibre in 28% (most of them reducing the intake of fruits and vegetables), alcoholic drinks (17%) and carbonated drinks (11.5%). No statistically significant differences were found in the elimination of food from the diet according to age, sex or type of IBD. No differences were observed in the elimination of dairy products, carbonated drinks or alcoholic beverages depending on the type of IBD, being more frequent the elimination of fibre in patients with UC (7/10 patients) than in CD. Regarding the role of their attending physician, 77.5% (86 patients) thought that nutrition was important for their doctor and/or nurse dedicated to IBD, although only 52.6% (61 patients) believed they had received enough information for their pathology.

Conclusion

The health professionals dedicated to IBD should increase our efforts to properly inform patients about nutritional aspects, since in our experience more than a half of patients avoid one or more foods (without scientific evidence to support it). Furthermore, only 52.6% consider that they receive sufficient information regarding this matter.
P423 NF-kB as a prognostic marker of response to biologic therapy in children with IBD
Authors: Radigina T , Illarionov A , Kuptsova D , Potapov A , Petrichuk S , Fisenko A P
Published: January 2020

Background

The transcription factor NF-kB is a regulator of innate and adaptive immunity through the activation of various pro and anti-inflammatory mediators. The aim of this study was to assess the prognostic value of changes in the level of NF-kB translocation in lymphocyte populations in response to infusion of TNF blockers in children with IBD.

Methods

There were examined 44 children with IBD (27-CD, 17-UC) and 20 conditionally healthy children aged 3–18 years. Patient status (exacerbation, remission) was assessed by the PUCAI (UC) and PCDIA (CD) indices. There were determined the percentage of cells with NF-kB translocation in populations CD3+CD4+ (Th), CD3+CD8+(Tc), CD3-CD19+ (B cells), CD3-CD16 / 56+(NK cells), CD3+CD4+CD161+ (Th17), CD3+CD4+CD25highCD127low (Tregs) with NF-kB translocation kit using flow cytometry ImageStreamX MKII (Amnis) before infusion of TNF blockers (infliximab, adalimumab), one day after infusion and after 6 months therapy. Statistical evaluation was performed using a nonparametric Mann–Whitney test. The results are presented as the median per cent of cells with NF-kB translocation (Me [Q 0.25-Q 0.75]).

Results

It was observed an increased level of NF-kB translocation in B-lymphocytes (Me 64 [53–81] – Me 38 [33–45]; p = 6 × 10−5), NK cells (Me 40 [33 -55] – Me 21 [18–26]; p = 4x10-4), Tc (Me 20 [15–24] – Me 16 [13–17]; p = 0.03), Th17 (Me 23 [21–28] – Me 18 [16–19]; p = 0.005) in children with exacerbation compared with remission. The level of NF-kB translocation in populations of lymphocytes during the period of clinical endoscopic remission did not differ from conditionally healthy children. The correlation between the level of NF-kB translocation and the number of cells in the studied lymphocyte populations was not found. In children with IBD after infusion of TNF blockers, a decrease the level of NF-kB translocation in NK cells was observed (Me 27.3 [23.5–39.1] – Me 17.7 [16.5–26.5]; p = 0,03) and an increase in Tregs (Me 18.9 [16.91–20.8] – Me 26.9 [19.4–31.9]; p = 0.0015).

Conclusion

The level of NF-kB translocation reflects the functional activity of major and small populations of lymphocytes. An increase in activity of Tregs in response to the administration of TNF blockers allows predicting a positive outcome from therapy over the next 6 months. If there is no Tregs reaction in response to the administration of TNF blockers, treatment tactics should be reassessed.