bluuebunny/crossref_metadata_2025_split huggingface dataset:
P657 Evolution of Crohn’s disease progression and surgery rates over 10 years for patients who initiated biologic treatment early compared with late or no biologic initiation
Authors: Pillai N , Dusheiko M , Maillard M , Michetti P , Pittet V 
Published: January 2020

Abstract

Background
This study aimed to evaluate the clinical outcomes for adults diagnosed with Crohn’s disease (CD) who started biologic treatments within 2 years of diagnosis (early initiation) compared with those who started biologics &gt;2 years after diagnosis or who did not receive any biologic treatment during the period of observation (late/no biologic initiation).

Methods
We conducted a retrospective analysis using 10 years of follow-up data from patients included in a national cohort study. We used propensity score methods to match patients in the early vs. late/no biologic initiation groups based on key baseline patient and clinical characteristics. Kaplan–Meier time-to-event models were used to evaluate the risks of intestinal resection surgery, fistula, stricture, and disease flares for each group. In addition, a subgroup analysis was performed stratifying patients known to have initiated biologic treatments into early (≤2 years after diagnosis) vs. late (&gt;2 years after diagnosis) initiation groups.

Results
In total, 411 patients were matched in the early initiation (n = 230) vs. late/no initiation (n = 181) groups. Two years after diagnosis, early biologic initiators had a 12% lower probability of intestinal resection surgery, a 9% higher probability of disease flares and fistulae, and a 5% higher probability of strictures compared with the late/no biologic initiators (Figure 1). After 10 years, the overall difference in the cumulative probability for each event were not statistically significant between the two groups. In the subgroup analysis, patients who initiated biologics early had a lower overall probability of stricture (p &lt; 0.01), disease flares (p &lt; 0.01), and intestinal resection surgery (p = 0.72), and a higher probability of fistula (p = 0.74) 10 years after diagnosis when compared with the group of patients who initiated biologics late.

Conclusion
This study found no significant differences in the long-term cumulative probabilities of intestinal resection surgery, fistula, stricture, and disease flares amongst CD patients who initiated biologic treatment early compared with similar patients who initiated biologic therapy late or who had not started any biologic treatments. However, in a subgroup of patients known to receive biologic treatments, early initiation was associated with significantly lower overall risks of strictures and disease flares. These results highlighted the need for more individualised care in CD in order to target aggressive treatment approaches to patients who show early signs of a complicated disease course.
P660 Evaluating the effectiveness of disease assessment at 2 weeks following a course of oral steroids: Does early intervention affect outcomes?
Authors: Slater J , ALGIEDER A , Jones J , Bates B , De Silva S 
Published: January 2020

Abstract

Background
Early intervention in those patients not responding to a course of oral steroids following an Acute flare of their IBD is essential for improved outcomes. It enables re-assessment and escalation of treatment in those that are non-responders. We present our data on the effectiveness of an IBD nurse-led telephone follow-up appointment two weeks after commencing a course of oral steroids and its impact on outcomes.

Methods
Data collected prospectively on all patients treated with oral prednisolone between March and November 2019. Partial Mayo score for ulcerative colitis (UC) and clinical assessment of symptoms for Crohn’s disease (CD) patients were used to assess response to treatment at 2 weeks.

Results
57 patients were treated with a Prednisolone reducing regime during the 8 months period. Patient demographics included 27 males and 30 females,19 CD and 38 UC patients with a median age of 48 (range 16–88). Following 2 weeks of treatment, 54% (31) of patients reported an improvement in symptoms-19 UC patients (Partial Mayo 0–4) and 12 CD patients. However, 45% (26) patients did not have a clinical improvement at week 2, 19 UC (Partial Mayo 2–9) and 7 CD were still symptomatic. In those patients who had not responded 3 were commenced on Azathioprine, 6 on Methotrexate and one patient had a slow response to steroids. Seven patients were escalated to receive biological therapy (3 vedolizumab, 2 infliximab, 1 ustekinumab and 1 adalimumab). Two other patients had their dose of vedolizumab increased, one patient was switched to another class of biologics. Three patients had a Flexible Sigmoidoscopy and following that 2 were admitted to receive IV steroids and escalated to biological therapy and Methotrexate. One patient was directly admitted for biological therapy, and 2 patients had an alternative diagnosis of Bile Salt Malabsorption which was treated. At the 3 months follow-up period all patients were well and had avoided further admissions or surgery, with only one patient electively opting for surgery.

Conclusion
Our data show that following a course of oral steroids for a flare of IBD, 45% are still symptomatic after 2 weeks. In this cohort, optimisation of treatment occurred in 23 patients (88%) with either the introduction of biological agents, or early introduction of immunomodulatory therapy. We believe that These data supports the implementation of an early review with appropriate intervention, demonstrating improved patient outcomes.
P666 Neutropenia in inflammatory bowel disease patients on TNF inhibitors: A single-centre, retrospective cohort study
Authors: AlAskar D , Mais A , Al Sulais E , Alameel T 
Published: January 2020

Abstract

Background
Tumor necrosis factor-α inhibitors (TNFi) have become the mainstay of treatment in moderate to severe cases of IBD.
The haematological safety profile of these agents has been documented in multiple clinical trials and post-marketing registries. Nonetheless, neutropenia has been reported in patients receiving TNFi for IBD and other diseases (Bessissow et al 2012).
In this study, we aim to ascertain the relationship between the use of TNFi and the development of neutropenia in IBD patients.

Methods
This is a retrospective cohort study including all adult IBD patients receiving TNFi at our centre from the year 2007 to 2018. Our primary outcome was the development of any neutropenic episode after starting a TNFi. Neutropenia was defined as circulating absolute neutrophil count (ANC) less than 1500/mm3.
For our secondary outcomes, we evaluated the impact of concomitant use of (5-ASA) or an immunomodulator on the risk of developing neutropenia. We also looked at the effect of baseline neutrophil and WBC counts on the subsequent development of neutropenia.

Results
A total of 292 patients met the inclusion criteria, 11 patients were excluded for not having neutrophil count done. The final analysis included 281 patients. The mean age of patients in this study was 33. Adalimumab was the most frequently prescribed TNFi. Of those included, 96 patients (34.2%) developed at least one episode of neutropenia while on a TNFi. The majority of these episodes (67.7%) were mild with ANC between 1000 and 1500/mm3. There was no significant difference in the age, gender, agent used or type of IBD between those who developed neutropenia and those who did not. On the other hand, baseline neutrophil count and concomitant use of azathioprine and 5-ASA were significant independent predictors of neutropenia after commencing TNFi. (Table 1).

Conclusion
In this study, mild neutropenia was common amongst IBD patients on TNFi. Patients were more likely to develop neutropenia if they have been on concurrent therapy with an immunomodulator or 5-ASA. Future prospective studies are required to further clarify the significance of neutropenia in IBD patients receiving TNFi.
P668 Real-life comparison of different anti-TNF biologic therapies for ulcerative colitis treatment: A retrospective cohort study
Authors: Barberio B , Zingone F , D’Incà R , Marinelli C , Maccarone M C , Gubbiotti A , Cingolani L , Lorenzon G , Ghisa M , Savarino E V 
Published: January 2020

Abstract

Background
Currently, ulcerative colitis (UC) can be treated with different anti-Tumor Necrosis Factor (TNF) drugs, which selection is mainly based on physician’s perspective. Indeed, head-to-head comparison studies evaluating the effectiveness and tolerability of anti-TNF drugs are lacking. The aim of this study was to compare the effectiveness and tolerability of anti-TNF-α drugs used in clinical practice in a cohort of patients with moderate to severe UC.

Methods
Retrospectively, 122 UC patients treated with Infliximab (IFX) Originator and Biosimilar, Adalimumab (ADA) and Golimumab (GOL) were included. We performed an intention to treat analysis to evaluate the clinical response, clinical remission, steroid-free clinical remission and endoscopy response according to the different time-points of the follow-up (ie. after induction, at 30 and 52 weeks). Baseline and post-induction predictor factors of these outcomes were evaluated using multivariate logistic regressions models. Data were analyzed using STATA11 software.

Results
Overall clinical response was 79.5% after induction, 79.5% at 30 weeks, 75.4% at 52 weeks, while the overall steroid-free clinical remission was 42.6%, 45.1%, 55.7%, respectively. After induction, a higher rate of treatment failure was observed in GOL group. Moreover, at the end of follow-up, lower rates of steroid-free clinical remission and clinical response were obtained by GOL (38.7% and 54.8% with p = 0.006 and p = 0.003, respectively). At week 52, endoscopic response was achieved by 46.5% of the population (IFX Originator: 46.7%; IFX Biosimilar: 40%; ADA: 51.6%; GOL: 22.6%; p = 0.003).

Conclusion
Among the different anti-TNF treatment, moderate-to-severe UC seems to respond better to IFX and ADA, whereas GOL seems to be less effective, despite a similar good safety profile. Current possibility of optimising also GOL will clarify whether these discrepancies are due to reduced drug exposure to GOL.
P669 Adherence to self-administered biologic therapies in inflammatory bowel disease: Experience in a tertiary hospital
Authors: Ramos Lopez L , Ramos Rodríguez J , De La Barreda R , Guitierrez F , Nazco Casariego G J , Alonso Abreu I , Carrillo Palau M , Quintero E 
Published: January 2020

Abstract

Background
Nonadherence to medications is common in patients with inflammatory bowel disease (IBD) and can result in disease complications, therapy escalation, and the need for corticosteroids. The aim of this study was to assess adherence to self-administered (subcutaneous) biologic medications prescribed for IBD and to identify risk factors for biologic nonadherence.

Methods
A retrospective cohort study was performed on IBD patients starting and receiving subcutaneous biologic therapies from January 2016 to July 2019. Medical records were retrospectively reviewed and demographic and IBD data were collected. A modified medication possession ratio (mMPR) was calculated for the first 12-month treatment and at the end of follow-up (global-42 months). Nonadherence was defined as mMPR of less than 90%. Multiple regression analysis was performed to assess risk factors associated with non-adherence therapy

Results
A total of 154 patients (84M/70F; mean age starting biologic treatment 36 ±14 years; Crohn’s disease n = 118/ ulcerative colitis n = 31/ indeterminate colitis n = 5) were included; 121 received Adalimumab (ADA) and 33 were on Ustekinumab (UST); 63% of patients were naive to anti-TNF and 16.9% had received &gt;2 previous biological treatment. Mean time from IBD diagnosis to use of subcutaneous biological agent was 16 ± 10 months. Mean time of subcutaneous agents use was 17.6(SD11.0) and 17.08 (SD6.8)months for ADA and UST, respectively. Global nonadherence (n = 154) (≤90% mMPR) was 6.6% for all patients receiving subcutaneous treatment and 6.3% for ADA and 6.5% for UST. Nonadherence during first 12-month treatment (n = 98) was 6.1% for all patients and 2.7 % for ADA and 16% for UST, respectively. In the multivariate analysis, Ustekinumab use was independently associated with higher nonadherence only for first 12-months adherence (OR 6.7, 95% CI 1.1–39.5).

Conclusion
Self-administered biologic treatment showed adequate global adherence in our study. Using subcutaneous administration for biologic agents in IBD patients forces us to monitor and control their adherence to ensure the therapeutic benefit.
P670 Usefulness of monitoring the concentration of azathioprine metabolites in the children with inflammatory bowel disease and autoimmune hepatitis
Authors: Bąk-Drabik K , Duda-Wrońska J , Dąbrowska-Piechota D , Adamczyk P 
Published: January 2020

Abstract

Background
Azathioprine (AZA) is an immunosuppressive drug, which is metabolised in the liver and kidneys into 6-thioguanine- the form responsible for the therapeutic effect. Despite its anti-inflammatory, antibacterial and immunomodulating properties, azathioprine has also dose-related side effects, such as bone marrow suppression, liver damage and pancreatitis. The purpose of this study was to assess the usefulness of monitoring the concentration of azathioprine metabolites: 6-tioguanine (6-TG) and 6-methylmercaptopurine (6-MMP) in the group of paediatric patients with inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH).

Methods
The clinical data of 46 paediatric patients (24 girls) with IBD and AIH, aged 8–17 years, hospitalised in the Department of Gastroenterology, who had undergone a blood examination for AZA metabolites concentration, were analysed.

Results
Initial mean dose of azathioprine was 1.23 mg/kg/day in IBD and 1.16 mg/kg/day in AIH. In 30% of patients, the concentrations of 6-TG and 6-MMP were within the normal range. Forty-eight per cent of patients required a dose change due to: elevated 6-TG concentration (32.6%) or underdosage (15.4%). After modification the mean dose was 1.16 mg/kg/day in IBD and 0.85 mg/kg/day in AIH. In 10.7 % of patients, the concentrations of 6-TG and 6 MMP were below the proper range, in the same percentage of patients metabolites were undetectable.

Conclusion
In a significant number of cases monitoring the concentration of AZA metabolites indicated the necessity to reduce the dose of AZA allowing to achieve the therapeutic optimum and prevent serious side effects. Receiving undetectable concentration of metabolites is a sign of non-compliance. The final doses of AZA were found to be lower than the recommended doses. Therapeutic drug monitoring (TDM), which involves measurement of drug or active metabolite levels is a good strategy that can be used to optimise IBD and AIH therapeutics.
P673 Strategy of selecting anti-TNF agent in patients with Crohn’s disease: A multi-centre retrospective cohort study by the Osaka gut forum
Authors: Amano T , Shinzaki S , Tashiro T , Otake Y , Tani M , Yoshihara T , Iwatani S , Tsujii Y , Inoue T , Hayashi Y , Iijima H , Takehara T 
Published: January 2020

Abstract

Background
Previous reports showed that disease activity before treatment affected long-term continuation of anti-tumour necrosis factor (anti-TNF) therapy in patients with Crohn’s disease (CD). However, there is no consensus about which anti-TNF agent should be selected dependent on patient’s condition. The aim of this study was to investigate factors affecting the continuation period of anti-TNF therapy and to clarify how to select each anti-TNF agent in patients with CD.

Methods
This was a retrospective multicenter cohort study of consecutive patients who started anti-TNF therapy (infliximab: IFX or adalimumab: ADA) as an induction therapy from January 2010 to March 2019 at 16 hospitals participating in the Osaka Gut Forum. We excluded patients who did not respond to therapy or had toxic events within 8 weeks. Factors affecting the continuation period of each anti-TNF agent such as backgrounds, blood tests, clinical features before treatment and concomitant medications were analyzed by the Cox proportional hazards model. The cumulative continuation rate of each agent was analyzed by the Kaplan–Meier method and evaluated by log-rank test.

Results
A total of 250 patients were enrolled (IFX /ADA; 138 /148 treatments, bio-naïve; 73%, median age; 36 years [Interquartile range (IQR); 24–46], median disease duration; 2.0 years [0.0–11.0], median observation period; 4.5 years [3.9–5.0]). Median Harvey–Bradshaw Index (HBI), C-reactive protein (CRP) and Albumin (Alb) were 5 [3–8], 0.71 mg/dl [0.14–2.04] and 3.5 g/dl [3.0–4.0], respectively. In patients with Alb ≥3.5 g/dl before treatment (median value), patients treated with IFX showed no significantly higher continuation rate than those with ADA. However, in those with Alb &lt;3.5 g/dl, patients treated with IFX (N =82) showed significantly higher continuation rate than those with ADA (N = 50) (p = 0.007). In the observation period, 50%/34% of patients treated with IFX /ADA increased dose and 29% /38% of them concomitantly used azathioprine. In patients with Alb &lt;3.5g/dl, by univariate analysis, stricturing and penetrating disease (B2 and B3/B1) [hazard ratio (HR); 4.18, 95% Confidence interval (CI); 1.83–12.0], disease duration [HR; 3.57, 95% CI; 1.16–9.77], and IFX/ADA [HR; 0.48, 95% CI; 0.28–0.83] were extracted as factors affecting continuation period of anti-TNF therapy. Furthermore, B2 and B3/B1 [HR; 3.80, 95% CI; 1.60–11.2] and IFX /ADA [HR; 0.49, 95% CI; 0.26–0.92] were extracted by multivariate analysis. After 8 weeks after treatment, the increase in Alb level was significantly higher in patients with IFX than those with ADA (p = 0.006), although there was no difference in HBI and CRP.

Conclusion
When serum Alb level is less than 3.5 g/dl before treatment, IFX can be used longer than ADA for CD patients.
P682 Faecal calprotectin and C-reactive protein levels are associated with long-term clinical and endoscopic outcomes: Analysis of the OASIS open-label extension trial of etrasimod for ulcerative colitis
Authors: Yarur A , Chiorean M , Zhang J , Reinisch W , Vermeire S , Panés J , Peyrin-Biroulet L , Sands B E , Cabell C H , Naik S U , Sandborn W J 
Published: January 2020

Abstract

Background
Reliable biomarkers of ulcerative colitis (UC) disease activity may be useful in clinical trials and practice. Etrasimod is an oral, selective, sphingosine 1-phosphate receptor modulator with efficacy in a 12-week, phase 2, double-blind (DB), randomised, controlled trial in adult patients with moderately-to-severely active UC (OASIS; NCT02447302). Patients who completed the DB study were eligible to enrol in an open-label extension (OLE; NCT02536404) and receive etrasimod 2 mg once daily for up to an additional 34 weeks. The aim of this post-hoc analysis was to assess the correlation of sequential faecal calprotectin (FC) and C-reactive protein (CRP) levels throughout the DB study and OLE with clinical and endoscopic outcomes at end of treatment (EOT) in the OLE.

Methods
In the DB study, patients received etrasimod 1 mg, etrasimod 2 mg or placebo. The OLE evaluable cohort comprised patients who received etrasimod 2 mg throughout the OLE. The modified intention-to-treat (mITT) population comprised patients with non-missing assessments. EOT was the last observation for each patient, occurring at week 46 (OLE week 34) for study completers or at last visit for patients who discontinued or had missing data. Endpoints were modified Mayo Clinic score (mMCS; range 0–9; including endoscopy, rectal bleeding [RB], and stool frequency [SF]); clinical remission (endoscopic subscore ≤1 [with absence of friability], RB ≤1, and SF score ≤1 with ≥1 point decrease from DB baseline); clinical response (clinical remission or decrease in mMCS of ≥2 points and ≥30% decrease from DB baseline, with either a RB decrease of ≥1 or RB score of ≤1); and endoscopic improvement (subscore ≤1). FC and CRP were measured longitudinally to EOT. Comparisons between subgroups were assessed with a Wilcoxon rank-sum test (2-sided P values). Analysis of correlation between variables was conducted using the Spearman’s rank coefficient.

Results
The evaluable cohort included 105 patients, 31 of whom received etrasimod 2 mg throughout both DB and OLE periods. At EOT 70%, 35% and 45% of patients in the mITT evaluable cohort had clinical response, clinical remission and endoscopic improvement, respectively. Differences in FC and CRP levels between patients with and without clinical remission at EOT are shown in Figures 1 and 2, respectively for patients who received etrasimod 2 mg throughout both the DB and OLE periods. Correlation analyses of FC and CRP with clinical (mMCS) and endoscopic disease activity and with each other are shown in Table 1.

Conclusion
FC and CRP appear to correlate with clinical and endoscopic outcomes over long-term treatment with etrasimod. Additional validation is needed to determine their utility in treat-to-target management strategies.
P694 Validation of two commercial assays for therapeutic drug monitoring of adalimumab biosimilars
Authors: Berghmans R , Naudts J , Ferkinghoff B , Gören H , Henke M L , Lennerz A , Van Stappen T 
Published: January 2020

Abstract

Background
Therapeutic drug monitoring of adalimumab (ADM) is increasingly used to optimise the management of patients with inflammatory bowel disease. The recent settlements with Abbvie concerning Humira®, paved the way for biosimilar drugs to enter the European market. In this study, we aimed to validate two commercial assays, the RIDASCREEN® ADM Monitoring (ELISA; also known as the apDia Adalimumab ELISA) and the RIDA®QUICK ADM Monitoring (rapid assay), which were developed and validated using the originator drug, for the quantification of two ADM biosimilars, AMGEVITA® and Imraldi®.

Methods
To validate the RIDASCREEN® ADM Monitoring, accuracy and recovery were determined by diluting AMGEVITA® and Imraldi® to varying concentrations within the clinical measuring range and in comparison with Humira®. The specification of accuracy is met when the deviation of the measured ADM biosimilar value is within ±15% of the theoretical value. For the recovery, the deviation of the measured ADM biosimilar value has to be within ± 15% of the Humira® value. To validate the RIDA®QUICK ADM Monitoring for the quantification of AMGEVITA® and Imraldi®, the recovery and linearity was determined. The recovery was determined by spiking three samples containing a low concentration of ADM biosimilar with varying concentrations of ADM biosimilar. The rapid assay complies with the requirements of recovery, if the observed value of ADM biosimilar is within ± 20% of the expected value of ADM biosimilar. The linearity was performed on the basis of NCCLS-guideline EP6-A; a sample with high concentration of ADM biosimilar was diluted 1:1 to 1:38.4. All samples were measured in the ELISA and rapid assay following manufacturer’s instructions.

Results
In the RIDASCREEN® ADM Monitoring, the mean deviation of the measured AMGEVITA® and Imraldi® value vs. the theoretical value was −6.6% and 2.1%, respectively. Recovery of spiked AMGEVITA® and Imraldi® samples in serum revealed a maximum absolute deviation of 12.9% and 14.8% vs. Humira®. In the RIDA®QUICK ADM Monitoring, the mean recovery of three serum samples spiked with varying concentration of AMGEVITA® and Imraldi® ranged from 91% to 115%, and 95% to 101%, respectively. Linearity was shown for both AMGEVITA® and Imraldi®.

Conclusion
We successfully validated the biosimilars AMGEVITA® and Imraldi® in the RIDASCREEN® ADM Monitoring and RIDA®QUICK ADM Monitoring. These results encourage therapeutic drug monitoring of ADM biosimilars in routine clinical practice.