bluuebunny/crossref_metadata_2025_split huggingface dataset:
P257 Assessment of the nutritional status of pediatric Inflammatory Bowel Disease patients according to disease activity
Authors: Palomino Pérez L M , Velasco Rodríguez-Belvis M , Cañedo Villaroya E , Vazquez Gómez J A , Muñoz Codoceo R A 
Published: May 2021

Abstract

Background
To determine the nutritional status in patients with inflammatory bowel disease (IBD) and its possible relationship with the activity of the disease.

Methods
A cross-sectional and descriptive study of paediatric patients with previously diagnosed or suspected IBD who underwent upper endoscopy (EGD) and colonoscopy, blood tests, stool analysis and MR Enterography (MRE), from October 2018 to February 2020.

Results
We recruited 21 patients and 12 of them were males (57%). A total of 12 patients had Crohn ́s disease (CD) (57%), 3 had ulcerative colitis (UC) (14%), 6 had IBD unclassified (IBDu) (28%). The age at the time of the evaluation was 14.2 ± 0.7 years and the progression time of the disease was 3.9 ± 0.6 years. A total of 16 patients showed clinical remission (76%), and 6 of them (28%) also had endoscopic and histological remission. Eight patients were receiving biological treatment (38%).
Rotavirus, adenovirus, Clostridium difficile toxin analysis and stool culture were performed in 14 patients, all of them were negative. The weight was 55.7 ± 20.71 kg, the size was 159.1 ± 15.0 cm and the BMI was 21.5 ± 5.6. A total of 7 patients (58%) had malnutrition, 3 (14%) were overweight and 2 (10%) were obese. We found no significant differences in BMI according to the underlying diagnose.
The results of the blood analysis with nutritional profile were: folic acid 12.3 ± 7.2 ng/ml, vitamin B12 455.2 ± 200.6 pg/ml, ferritin 36.9 ± 16.7 ng/ml, total protein 7.6 ± 0.5 g/dl, albumin 4.4 ± 0.4, prealbumin 22.7 ± 7.0 mg/dl, retinol binding protein 2.2 ± 1.0 mg/dl, vitamin A 0.3 ± 0.1 mg/L, effective vitamin E 4.6 ± 0.7 mg/g, 25(OH) vitamin D 20.1 ± 6.2 ng/ml, vitamin B1 6.1 ± 1.2 mcg/dL, vitamin B6 28.3 ± 9.8 ug/L, IFG-1 312.1 ± 124.1 ng/ml, IGFBP-3 4.4 ± 0.6 μg/ml, PTH 54.9 ± 2.7, Selenium 88.7 ± 23.1, Zinc 99.4 ± 9.3, copper 96.0 ± 11.5 ug/dL.
We found a significant negative correlation between the IGF-1 levels and the SES-CD values, and between prealbumin levels and Mayo score values (p &lt; 0.05). However, no significant correlations were found between other nutritional values and endoscopic scores. We found a significant negative correlation between the BMI values and the shPCDAI (p &lt; 0.05), but no significant correlation was found with PUCAI. No differences in analytical markers or BMI were found between patients receiving biological treatment and those who were not.

Conclusion
More than half of the teenager patients with IBD showed some kind of nutritional disturbance. The analytical nutritional markers which related more closely to the endoscopic activity were IGF-1 and prealbumin. The alteration of the clinical score was related to alterations in the BMI in CD but not in the UC patients.
P259 Safety, tolerability and pharmacokinetics of BT051, an oral inhibitor of neutrophil migration and activation in clinical development for Inflammatory Bowel Disease
Authors: Murphy C , Stevens C , Hershberger E , Quintas M , Miller B , Ghahramani P 
Published: May 2021

Abstract

Background
BT051 is an oral, locally acting inhibitor of neutrophil trafficking and activation in clinical development for the treatment of patients with Inflammatory Bowel Disease (IBD). Herein we report the results of this first-in-human study of BT051 in healthy subjects.

Methods
This was a phase 1, randomised, double-blind, placebo-controlled, single-centre, single ascending dose (SAD) study. Healthy subjects (n=50) were randomised into 5 SAD cohorts to receive BT051 (100, 300, 700, 1500 or 3500 mg) or placebo (8 active:2 placebo in each cohort). A safety review committee evaluated any dose-limiting adverse events (AEs) through Day 3 before proceeding to the next cohort. Samples for pharmacokinetic (PK) analysis were collected from blood, stool and urine predose and up to 48 hours postdose; stool samples for PK analysis were also collected on Day 7. An exploratory endpoint of systemic immunosuppression was performed by assessing cytokine secretion induced from T-cells in subjects’ peripheral blood mononuclear cells (PBMC) at 4 and 24 hours postdose.

Results
Fifty healthy subjects were dosed with BT051 (n=40) or placebo (n=10). No dose-limiting toxicities, serious AEs or study discontinuations due to AEs were observed. Nine (22.5%) BT051 subjects and 2 (20%) placebo subjects experienced at least 1 mild or moderate AE with only vessel puncture site pain and constipation reported in more than 1 subject (n=2). Mean % of dose excreted in stool from partial collection ranged between 11.3–26.3%. At all doses tested, concentrations of BT051 in the large intestine were estimated to exceed &gt;20x the threshold for inhibition of neutrophil transmigration and activation in vitro (1 μM) and continued to be detected out to 7 days postdose. Generally, blood concentrations of BT051 were undetectable except in two subjects at one time point each: one subject at 24 hours postdose who received 700 mg BT051 (70 ng/mL) and another subject at 12 hours postdose who received 1500 mg BT051 (8 ng/mL). Mean % of dose excreted in urine through 48 hours postdose ranged between 0.01–0.03%. No evidence of systemic T-cell immunosuppression was observed at any dose level.

Conclusion
Single ascending doses up to 3500 mg of BT051 were safe and well-tolerated in healthy subjects. Stool concentrations out to 7 days postdose that exceed the expected efficacious threshold, minimal to no systemic exposure and the lack of systemic immunosuppression support the continued development of BT051 as a gut-targeted therapy for patients with IBD.
P263 Influence of Crohn′s Disease phenotype in the retention rate of ustekinumab treatment: SUSTAIN Study
Authors: Chaparro M , Bastón Rey I , Fernández-Salgado E , González García J , Ramos L , Diz-Lois Palomares M T , Argüelles F , Iglesias Flores E , Cabelo M , Rubio Iturria S , Núñez Ortiz A , Charro M , Ginard D , Dueñas Sadornil C , Merino Ochoa O , David B , Iyo E , Gutiérrez Casbas A , Ramírez de la Piscina P , Boscá-Watts M M , Arroyo M , García M J , Hinojosa E , Gordillo J , Martínez Montiel P , Velayos Jiménez B , Quílez Ivorra C , Vázque morón J M , Huguet J M , González Lama Y , Muñagorri Santos A I , Amo V M , Martín Arranz M D , Bermejo F , Martínez Cadilla J , Fradejas Salazar P , Novella C , Vispo E , Barreiro-de Acosta M , Gisbert J P 
Published: May 2021

Abstract

Background
Crohn′s disease (CD) is a progressive inflammatory bowel disease that can lead to complications such as strictures or penetrating disease, and ultimately surgery, representing a complex clinical challenge in the care of patients. We aimed to evaluate the influence of CD phenotype in the retention rate of ustekinumab in the Sustain study.

Methods
Retrospective, multicentre study (&gt;60 sites) including patients with active CD [(Harvey-Bradshaw (HBI)&gt;4)] who received ≥1 dose of ustekinumab intravenously before July 2018. Clinical remission was defined as HBI≤4 and response as ≥3 points decrease from baseline. Loss of response (LoR) was defined as reappearance of symptoms that led to intensifying the treatment dose, adding another medication to control CD, switching or surgery in patients with short-term remission.
Disease characteristics were collected (date of diagnosis; location; behaviour: inflammatory, stenosing or penetrating; presence of perianal disease or extraintestinal manifestations; previous surgeries, etc.).
The retention rates in patients on ustekinumab depending of their disease phenotype were evaluated by descriptive analysis and Kaplan-Meier survival curves. Survival curves were compared using the log-rank test. Predictive factors were assessed by Cox-regression. Data quality was assured by remote monitoring.

Results
463 CD patients were included (Table 1).

87 patients (18.6%) had penetrating CD in our cohort.
The probability of maintaining UST treatment was 91% at 6, 83% at 12, 76% at 18 and 73% at 24 months.
Similar retention rates were observed in patients with inflammatory (77.6%), stricturing (76.4%) and penetrating (79%) disease behaviour (p&gt;0.05). Figure 1.

Conclusion
Ustekinumab has shown to be equally effective in the treatment of inflammatory, stricturing and penetrating CD phenotype in Sustain, the largest study evaluating its use in CD in clinical practice, having the longest follow-up period reported to date.
P264 Impact of the HLA-DQ1*05 alelle on the initial response to infliximab in patients with Inflammatory Bowel Disease
Authors: Suris Marin G , Santacana E , Padullés N , Padró A , Serra K , Ruiz A , Blat R , Arajol C , Sanchez E , Berrozpe A , Rodríguez-Alonso L , Rodríguez-Moranta F , Guardiola J 
Published: May 2021

Abstract

Background
HLA-DQA1*05 Carriage is associated with development of anti-drug antibodies to infliximab in patients With Crohn’s Disease (Sazonovs et al. Gastroenterology 2019). Our group has shown that the presence of this allele is also an independent predictor of secondary loss of response to infliximab (Guardiola J, ECCO 2019) and adalimumab (Guardiola J ECCO 2020). However, the impact of the HLA-DQA1 * 05 allele on the initial response and persistence of IFX in the first months of treatment is unknown.

Methods
This is a retrospective cohort study from a prospectively maintained data base at the Hospital Universitari de Bellvitge (third level teaching hospital) Patients with Crohn’s Disease (CD) or Ulcerative Colitis (UC) who initiated IFX to induce remission and who had been followed up for failure or a minimum of 6 months were included. Failure at IFX was defined as the need of escalation or change treatment, surgery, or hospitalization for the first 6 months.

Results
99 patients (65 MC, 34 CU) were included. In 63 (63.63%) IFX failed. 39 (39%) were carriers of the HLA-DQA1 * 05 allele. In multivariate analysis, HLA-DQA1*05 carriage (HR 1.9, 95% CI 1.14–3.31 p=0.015), the use of immunomodulators (HR 0.38, 95% CI 0, 23–0.66 p = 0.001) and suffering a CU vs. MC (HR 1.72, 95% CI 1.02–2.89 p = 0.041) were independent predictors of IFX failure. HLA-DQA1 * 05 was also associated with non-persistence of treatment (HR 2,4,95% CI1.45–3.99 p = 0.001). Figure A

Conclusion
HLA-DQA1*05 carriage is common in patients with IBD and it’s associated with a marked increase in the risk of loss of response to infliximab. Testing for HLA-DQA1*05 would allow treatment to be tailored according to the risk of loss of response.
P277 Frequency and effectiveness of empirical anti-TNF dose intensification in Inflammatory Bowel Disease: systematic review with meta-analysis
Authors: Guberna Blanco L , Nyssen O P , Chaparro M , Gisbert J P 
Published: May 2021

Abstract

Background
Loss of response to anti-TNF (tumor necrosis factor) therapies in inflammatory bowel disease occurs in a high proportion of patients. However, the precise incidence of dose intensification (DI) and its effectiveness remains unclear. Our aims were: 1) To evaluate the need of DI of anti-TNF therapy either by increasing the dose or decreasing doses’ interval; 2) To evaluate possible variables influencing its requirement; 3) To assess the effectiveness of empirical DI.

Methods
Bibliographical searches were performed in Pubmed, Embase, the Cochrane Library and CINAHL. Selection: prospective and retrospective studies assessing loss of response to anti-TNF therapy, considered as the need of DI, in Crohn’s disease (CD) and ulcerative colitis (UC) patients treated for at least 12 weeks with an anti-TNF drug [infliximab (IFX), adalimumab (ADA), certolizumab or golimumab]. Exclusion criteria: studies using anti-TNF as prophylaxis for postoperative recurrence in CD or those where DI was based on therapeutic drug monitoring. Data synthesis: Effectiveness by intention-to-treat (random effects model). Data were stratified by medical condition (UC vs. CD), anti-TNF drug and follow-up. Subgroup analyses were performed to explore heterogeneity.

Results
In total, 174 studies (32,031 patients) were included. The overall rate of DI requirement after 12 months follow-up was 27% (95%CI 23-31, I2=96%, 51 studies) in naïve patients and 38% (95%CI 31-46, I2=87%, 18 studies) in non-naïve patients. The rate of DI requirement was higher in patients with prior anti-TNF exposure (c²=6.5, P=0.01) and in UC patients (c²=4.7, P=0.03). The rate of DI requirement in naïve patients after 36 months follow-up was 35% (95%CI 27-43%; I2=98%; 22 studies). The overall short-term response and remission rates to empirical DI in naïve patients were 66% (95%CI 61-71%; I2=81%; 35 studies) and 48% (95%CI 35-62%; I2=97%; 27 studies), respectively. Subgroup analyses are presented in the tables.

Conclusion
Loss of response to anti-TNF agents ―and consequent DI― occur frequently in IBD (approximately in 1/4 at one year and in 1/3 at 3 years). DI requirement is higher in UC patients and in those with prior anti-TNF exposure. Empirical DI is a relatively effective therapeutic option.
P314 TNF gene activation used as criterion to discontinue biologic therapy – A patient series introducing the NovaPrime TNF kit
Authors: Goll R , Kay-Martin J , Viola A , Paulssen E , Moe Ø K , Cui G , Fries W , Florholmen J 
Published: May 2021

Abstract

Background
Severe inflammatory bowel disease can be successfully treated with biologic drugs such as anti-TNF. However, there is no consensus on if and how to stop treatment. Our group has earlier shown that normalization of TNF gene expression may be a beneficial prognostic factor when attempting to discontinue biologic therapy. We here present data from a series of patients in endoscopic remission and with normalized TNF gene expression.

Methods
Severe inflammatory bowel disease can be successfully treated with biologic drugs such as anti-TNF. However, there is no consensus on if and how to stop treatment. Our group has earlier shown that normalization of TNF gene expression may be a beneficial prognostic factor when attempting to discontinue biologic therapy. We here present data from a series of patients in endoscopic remission and with normalized TNF gene expression.
A total of 91 patients were recruited at hospitals in Norway and Italy: 55 patients (32 UC, 23 CD) in remission (picked by normalization of TNF using our in-house TNF qPCR), and for comparison: 14 patients with active disease, and 22 normal controls. Mucosal samples taken prior to drug discontinuation from all patients were re-measured for TNF mRNA by the NovaPrime TNF kit.

Results
A clear difference could be seen between normal controls and patients with active disease, showing highly elevated TNF mRNA values in the active disease group. The patients in remission had values resembling the normal controls with values generally below a cut-off of 9060 copies/µg total RNA by the NovaPrime TNF kit.

The patients in remission were followed for up to 5 years noting two endpoints: relapse triggering any adjustment of medication, and relapse triggering restart of biologics. Median survival time before adjusting medication was 12 months for ulcerative colitis and 17 months for Crohn’s disease. Median time to restart of biologics was 21 months (2 – 40) overall, and after 3 years 43% still were not in need of biologic therapy.

Conclusion
We conclude that the NovaPrime TNF kit yields consistent readings comparable to our in-house assay, and that this industrial standard kit enables any PCR lab to perform TNF gene expression in samples from intestinal mucosa. A considerable proportion of patients with normalized TNF gene expression can maintain long term remission without biologic therapy, relieving health care costs and potential side effects of long-term therapy.
P480 Assessing primary response to biologic therapy in Inflammatory Bowel Disease - ‘the when and the how?’
Authors: Moore A C , Peake S 
Published: May 2021

Abstract

Background
ECCO guidelines state that patients started on biologic therapy for Inflammatory Bowel Disease (IBD) should be reviewed between week 10 and 16 depending on the biologic used and response assessed using predefined objective criteria. The study aim was to ascertain, the time point, and by which methods patients with IBD are being assessed for primary response.

Methods
A retrospective chart review was conducted of 50 consecutive patients with IBD who had been started on biological therapy between October 2018 and June 2019 at a tertiary referral university teaching hospital in London, UK.

Results
Patients were started on 5 biologics; infliximab (20 patients), adalimumab (11 patients), vedolizumab (6 patients), ustekinumab (9 patients) and tofacitinib (4 patients). Twenty two patients had Ulcerative Colitis and 28 patients had Crohn’s Disease. All 50 patients were still receiving biological therapy at the time of their first assessment in a consultant led IBD clinic.
On average, patients were assessed at week 13 for primary response. Figure 1 outlines the time to assessment of disease response, according to the biologic used. The most frequently used methods were clinical symptoms (49 patients, 98%) and blood tests (47 patients, 94%). Disease activity scores were rarely documented. Other methods of disease assessment were faecal calprotectin (13 patients, 26%), ileocolonoscopy (11 patients, 22%) and radiological studies (2 patients, 4%). Only 19 patients (38%) had either a faecal calprotectin or a colonoscopy ordered at their appointment. Thirteen patients (26%) had undergone an endoscopic assessment of their disease when the data was analysed in December 2019.

Conclusion
Patients are being assessed in a timely fashion for primary response to biological therapy, in line with current ECCO guidelines. Clinical symptoms and blood tests are being heavily relied on to assess for primary response to therapy. Patient-reported symptoms do not correlate well with mucosal inflammation in IBD1. Faecal Calprotectin, as a surrogate marker of mucosal inflammation, and colonoscopy are being underused. Potential reasons for the low rates of colonoscopy may include patient’s wishes and lack of endoscopy capacity. The importance of a mucosal healing assessment is imperative to be able to optimise treatment appropriately and improve long-term outcomes for our patients.

Reference
P538 The reliability of patient performed fecal calprotectin testing
Authors: Crouwel F , Dijkhuis L E J L , Duijvestein M , Buiter H J C , De Boer N K , Hamer H M 
Published: May 2021

Abstract

Background
For measurement of fecal calprotectin (FC) a stool sample is sent to the laboratory, where calprotectin is extracted and determined. With the CALiaGold (CG) tube, especially designed for home sampling, this labor-intensive extraction procedure in the laboratory can be bypassed. Furthermore, the home-use of this buffer containing extraction device can potentially prevent FC degradation. We aimed to determine the reliability of patient performed FC extraction, to assess whether degradation during transport can be prevented and to determine its usability by patients.

Methods
In this prospective cross-sectional observational study, 4 CG tubes and 2 regular tubes were filled from the same bowel movement by patients with inflammatory bowel disease. Half of the tubes were directly frozen, others were sent to the laboratory by mail. Four more CG tubes were filled at the laboratory; 2 from the native sample sent by mail and 2 from the directly frozen native sample. The FC levels were measured by a particle enhanced turbidimetric immunoassay. The directly frozen tubes were used for the comparison between patient and analyst performed extractions, while the tubes sent by regular mail were used to determine FC stability during transport. The usability was assessed with a questionnaire.

Results
Fifty-three patients were included. No significant difference was found in patient performed extractions compared to analyst performed extractions in samples with FC levels &lt;200 µg/g. However, in samples with FC levels ≥200 µg/g patient performed extractions were significantly lower (p=0.014). When patients were divided in 3 groups (i.e. FC levels &lt;50ug/g, 50–200 µg/g and &gt;200 µg/g), the resulting Cohen’s kappa coefficient was 0.787 (95% CI: 0.646–0.928), reflecting a substantial agreement between patient and analyst performed extraction. A median FC increase of 28.6% was found in the native samples after one freeze-thaw cycle, potentially explaining the higher FC levels in the analyst performed extractions from the directly frozen native sample.
Patients sampling imprecision was higher (p&lt;0.01, median CV 17%) compared to the analyst (median CV 8%). Higher FC levels were found in the CG tubes sent by mail compared to native samples, reflecting less FC degradation. The questionnaire revealed that 62% of patients preferred the CG tube and 8% the conventional tube.

Conclusion
Patient performed FC extraction is a realistic alternative sampling method, especially since the freeze-thaw process in the native samples may have led to higher values in the analyst performed extractions. Moreover, usage may prevent FC degradation during transport and patients prefer the use of the extraction device.