bluuebunny/crossref_metadata_2025_split huggingface dataset:
P586 Higher infliximab and adalimumab trough levels are associated with fistula healing in patients with fistulising perianal Crohn’s disease
Authors: GU B , Venkatesh K , Williams A J , Ng W , Corte C , Ghaly S , Xuan W , Paramsothy S , Connor S 
Published: January 2020

Abstract

Background
Anti-TNF α agents, including infliximab (IFX) and adalimumab (ADA), are arguably the most effective medical therapies for fistulising perianal Crohn’s disease (CD). Increased rates of perianal fistula healing have been reported with increased IFX trough levels. Our study aimed to determine the correlation between perianal fistula healing and closure with IFX and ADA trough levels in fistulising perianal CD patients on maintenance therapy.

Methods
In this multi-centre retrospective cross-sectional study, we identified CD patients with perianal fistulae on maintenance IFX or ADA who had an IFX or ADA trough level within 3 months of clinical assessment. Data collected included demographics, serum IFX and ADA trough levels (mg/l) and concomitant medical and surgical therapy. The primary outcome was fistula healing, defined as a cessation in fistula drainage. The secondary outcome was fistula closure, defined as healing as well as closure of all external fistula openings. Receiver operating characteristic (ROC) curve analysis was performed to identify the IFX and ADA concentration cut-off points with combined maximal sensitivity and specificity that corresponded to fistula healing.

Results
A total of 123 patients (IFX = 72; ADA = 51) were included. Fifty-four (75.0%) patients on maintenance IFX achieved fistula healing and 22 (30.6%) achieved fistula closure. Patients who achieved fistula healing had significantly higher median IFX trough levels compared with patients who did not [6.2 (interquartile range 3.1 - 9.6) vs. 3.0 (0.3 - 6.2), (p = 0.007)]. The median IFX trough levels for patients with and without fistula closure were not significantly different [6.4 (2.9 - 9.8) vs. 4.9 (2.5 - 8.9), (p = 0.277)]. Forty (78.4%) patients on maintenance ADA achieved fistula healing and eighteen (35.3%) fistula closure. Patients who achieved fistula healing had a significantly higher median ADA level compared with those who did not [8.7 (6.6 - 12.0) vs. 5.4 (2.5 - 8.3), p = 0.007]. The median ADA trough levels for patients with fistula closure and without fistula closure were not significantly different [9.6 (6.7 – 12.0) vs. 7.7 (4.4–9.8), p = 0.098]. An IFX cut off point of 6.10mg/l was associated with healing (sensitivity 52%; specificity 78%; area under the curve (AUC) 0.72). An ADA cut off point of 7.05mg/l was associated with healing (sensitivity 70%; specificity 73%; AUC 0.77).

Conclusion
Higher IFX and ADA trough levels are associated with fistula healing. No association between IFX and ADA trough levels and fistula closure was seen, although larger numbers may be required. To the best our knowledge, this is the first study to demonstrate a significant association with both higher IFX and ADA levels with fistula healing in perianal CD.
P588 vedolizumab trough levels at week 6 and 14 correlate with clinical remission in inflammatory bowel disease patients
Authors: Marino M , Domenis R , Biribin L , Cifù A , Navarria L , Scardino G , Fabris M 
Published: January 2020

Abstract

Background
Vedolizumab (VDZ) is a therapeutic monoclonal antibody against α 4β 7 integrin approved for the treatment of inflammatory bowel diseases (IBDs). A relationship between VDZ exposure and clinical efficacy has been highlighted by several studies, but data are still controversial. In this perspective, our study aims to investigate the clinical usefulness of VDZ drug monitoring during the induction phase to support therapeutic management of IBD patients in the real life.

Methods
This retrospective study focus on a single cohort of 25 IBD patients (7 with Crohn’s disease and 18 with ulcerative colitis) treated with VDZ between 2016 and 2019. VDZ trough levels (TLs) and anti-VDZ antibodies (AVA) were measured before infusion at weeks 6, 14 and 22, using Promonitor® ELISA assays (Grifols). Disease activity was evaluated using international criteria, defining clinical remission when Mayo Partial Score &lt;2 and Harvey–Bradshaw Index &lt;5.

Results
VDZ TLs showed a significant inverse correlation with disease activity at each time point (week 6: Spearman’s rho = −0.659, p = 0.0003), (week 14: Spearman’s rho = −0.634, p = 0.0009), (week 22: Spearman’s rho = −0.476, p = 0.029). The median VDZ TLs was significantly higher in patients in clinical remission when compared with those with active disease, either at week 6 (42.3 vs. 19.8 µg/ml, p = 0.0005), and at week 14 (23 vs. 8.6 µg/ml, p = 0.003). Of note, at week 6, patients with VDZ TLs &gt;24 µg/ml were significantly associated with a state of clinical remission compared with those showing VDZ TLs &lt;24 µg/ml (9/12, 75% vs. 1/13, 7.7%; OR=36, [95% CI=3.19–401], p = 0.001). Anti-VDZ antibodies were detected in 1 patient out of 25 (4%).

Conclusion
VDZ TLs in the induction phase correlate with the clinical score in IBD patients, helping the management of the therapeutic efficacy of VDZ, from the very beginning of the biological treatment. In particular, at week 6, VDZ trough levels &gt; 24 µg/ml may represent a potential drug concentration target to achieve long-term remission.
P589 Longer-term outcomes in patients with Crohn’s disease who are primary non-responders to anti-TNF in a single UK centre
Authors: HODGES P , Saunders J , Betteridge F 
Published: January 2020

Abstract

Background
Primary non-response (PNR) is reported to occur in up to 24% patients with inflammatory bowel disease treated with anti-TNF drugs. The longer-term outcomes of these patients are less well documented however it is recognised that this group represents a significant treatment challenge. We report retrospective outcomes for these patients from a single centre.

Methods
All patients with Crohn’s disease who stopped anti-TNF therapy because of PNR from 2013 to 2017 were identified from our database. Data were retrospectively collected from electronic patient records.

Results
124 patients were started on anti-TNF therapy in this 4-year period and PNR occurred in 26 of these (21%). Median follow-up was 43.5 months.
Following PNR 9 (34.6%) patients had surgery as next treatment although in the majority of these cases (6/9) this was before alternative class biologic drugs were available. 7 (26.9%) switched to an alternative anti-TNF again with the majority of these (5/7) being prior to the availability of other biologic class drugs. The subsequent outcomes for these patients are; 3 remain in remission, 1 failed to respond to an alternative anti-TNF and went on to have surgery within 1 year, 1 was in remission for 2 years then switched to vedolizumab, 2 were lost to follow-up or died for unrelated reasons. 6 (23.1%) switched to a different biologic class. Of these, 4 remain in remission, 1 required subtotal colectomy within 3 years, and 1 had 3 further biologic agents all of which failed and is now awaiting a trial drug or surgery. 2 (7.7%) switched to other immunomodulators. Two (7.7%) were lost to follow-up.

Conclusion
Overall 11 of the 26 (42%) patients required surgery within 3 years of primary anti-TNF failure. These data span a period during which vedolizumab and ustekinumab became available; therefore, the proportion of patients requiring surgery as next intervention is likely to be less now that these alternative drugs are available. In this cohort 4/6 patients who received alternative biologic class drugs who would previously have gone on to have surgery as the next intervention remains in remission (median follow-up 37 months). Although this is a small cohort, PNR response is shown to be a marker of poor prognosis with the availability of alternative biologics appearing to reduce the short-and medium-term need for surgery.
P590 Outcomes of patients treated with sequential anti-TNF therapy in a tertiary referral centre
Authors: Rowan C , O’Donnell J , Cullen N , O’Toole A , Boland K 
Published: January 2020

Abstract

Background
Anti-TNF agents are administered intravenously(iv) or subcutaneously(SC).Factors such as speed of onset and patient preference influence that decision. The aim of this study was to assess the characteristics and outcomes of patients transitioned between iv and sc anti-TNF therapy.

Methods
Patients attending a single tertiary referral centre, treated with two different anti-TNF drugs were included. Patient and disease characteristics, biochemical, endoscopic and radiological data were collated.

Results
69 patients were included. Table 1 describes the patient cohort. 28 (40.6%) patients transitioned from SC anti-TNF to infliximab (IFX). N=35 (50.7%) switched from IFX to Adalimumab and 6 to Golimumab. 31 patients demonstrated some degree of endoscopic activity prior to anti-TNF switch;14/16 (87.5%) demonstrated radiological activity. 48 patients had endoscopic assessment post-switch; 28 (58.3%) had endoscopic remission.Of the 19 patients with post-transition imaging, 42.1% (8/19) had no active disease. 43 (79.6%) patients had therapeutic trough concentrations of the current anti-TNF. 13 (26%) were previously on combination therapy, while 22 (32.8%) currently are. 24 (39.3%) patients had detectable anti-drug antibodies to their prior anti-TNF, 10 (16.4%) had primary non-response and 12 (19.7%) had loss of response with adequate drug levels. There were significantly more patients with antibody formation in the group switching from IFX to SC anti-TNF (n = 20; p = 0.001). A significantly higher proportion of patients who were transitioned from IFX to SC anti-TNF currently have therapeutic/supratherapeutic drug levels when compared with patients transitioning SC to IFX (p = 0.01). There is no significant difference in the proportion currently on combination therapy (p = 0.668). There is a significant improvement in c-reactive protein, albumin and haemoglobin in the cohort as a whole. However, there is no significant difference in rates of clinical remission (p = 0.556) or endoscopic remission (p = 0.89) after switching from one mode of delivery to another.

Conclusion
Patients converted from IFX to SC anti-TNF have similar rates of endoscopic and clinical remission to those transitioned to IFX. However, many patients had previous antibody formation. Subsequently, this group has significantly higher rates of therapeutic or supra-therapeutic drug concentrations, suggesting the conscientious use of therapeutic drug monitoring to optimise response.
P593 Predictors of steroid-resistance in severe colitis of inflammatory bowel disease
Authors: JEMMALI C , Labidi A , Jouini M A , Hafi M , Serghini M , Fekih M , Boubaker J 
Published: January 2020

Abstract

Background
Intravenous steroids (IVS) remain the mainstay of therapy in severe colitis of inflammatory bowel disease (IBD), although 30 to 40% of patients will not respond. In such cases, rescue medical therapy with immunomodulators, or an early colectomy are considered. The aim of this study was to identify predictor factors of corticosteroid failure during severe colitis in IBD patients.

Methods
We conducted a 5-year retrospective study (2014–2019), including all IBD patients with severe colitis. Diagnosis was based on clinical, biochemical markers and endoscopic criteria. All patients received conventional first-line therapy with IVS. Corticosteroid failure was defined according to Travis criteria.

Results
A total of 40 patients with a mean age of 36 ± 13.1 years and a sex ratio H / F of 0.6 were included. Twenty-three patients (57.5%) had ulcerative colitis (UC) while 17 patients (42.5%) had Crohn’s disease (CD). The average duration of IBD in all patients was 28.8 ± 52.1 months. Severe colitis was the first flare of the disease in fifteen patients (37.5%). Twenty-seven patients (67.5%) respond to IVS. Factors associated with steroid failure on admission were type of IBD (UC) (p = 0.03), presence of fever (T≥ 38°C) (p = 0.04) and blood transfusion (p = 0.02). Biochemical predictors of steroid failure were low hematocrit rate (&lt;28%) (p = 0.03) and hypokalemia (K+&lt;3.5mmol/l) (p = 0.004). Upon 3 days of IVS, a reduction less than 40% in stool frequency, thrombocytosis (platelets&gt; 474000/mm3) (p &lt; 0.001), high-CRP level (&gt; 43mg/dl) (p = 0.026) are predictors of steroid failure. Upon 5 days of IVS, high-CRP level (&gt; 12,1mg/dl)(p = 0.021) was significantly associated with steroid failure.

Conclusion
In conclusion, stratification of risk in IBD patients with severe colitis should be considered early on admission and at the latest on day 3 of IVS in order to select patients at high risk of steroid failure and then decide to start rescue therapy.
P601 Development and validation of dried blood spot sampling as a tool to identify the best time point to measure predictive ustekinumab serum concentrations in patients with Crohn’s disease
Authors: Van den Berghe N , Verstockt B , Vandeput E , Ballet V , Gils A , Ferrante M , Vermeire S , Thomas D 
Published: January 2020

Abstract

Background
Therapeutic drug monitoring of ustekinumab (UST), a monoclonal antibody directed against the p40 subunit of IL12/23, can serve as a tool to identify underexposed Crohn’s disease (CD) patients, as UST concentrations have been linked to treatment response. Drug concentrations are most often measured when a patient is losing response. To reduce the risk of loss of response, drug concentrations could be measured upfront to predict the chance of achieving response later on and optimising treatment if necessary. Identification of the optimal time point to measure UST levels that have a predictive value for long-term outcome requires studies with multiple sampling. Dried blood spot (DBS) sampling allows convenient and remote collection of a blood drop through a small finger prick. The current study aimed to develop and validate the DBS method in order to identify the best time point to measure UST concentrations to predict long-term outcome in CD patients and explore the pharmacokinetic profile.

Methods
UST concentrations (0.2–80 μg/ml) were spiked in citrated whole blood and 40 μl was spotted onto protein saver cards. After punching a 6mm disc, DBS was extracted and the UST concentration was measured with an in-house developed MA-UST56A2D11/MA-UST56C1H12 ELISA. The extraction efficiency, accuracy, precision and the effect of anti-UST antibodies on UST detection were evaluated. Additionally, the effect of the spotted blood volume, the stability of the DBS card at room temperature (RT) and DBS extract at -20°C was examined. To evaluate the correlation between UST in DBS extracts and serum, DBS and serum were simultaneously collected from 8 UST-treated CD patients at two different time points.

Results
Spiking UST to citrated whole blood and subsequent spotting and extraction revealed an average extraction efficiency of 65 ± 9% (n = 11). The accuracy and imprecision of all concentrations tested were 92–109% and 11–18%, respectively. Addition of anti-UST antibodies to spiked UST samples caused a similar decrease in UST concentration in DBS extracts as in serum. Spotted blood volumes between 15 and 50 μl demonstrated similar recoveries. Storing the DBS card at RT for up to 2 weeks and DBS extract at -20°C for 2 months did not impair recovery. UST concentrations in DBS extracts (range: 0.55–12.1 μg/ml) from CD patients correlated strongly with those in serum (Pearson r = 0.982, p &lt; 0.0001).

Conclusion
DBS is a robust method that facilitates multiple sampling for the determination of UST concentrations in CD patients. To explore the pharmacokinetic profile of UST and identify the best time point during induction to predict the long-term outcome, a prospective study in which multiple DBS are collected in active CD patients initiating UST is warranted.
P602 Changes in emotional health and work-related outcomes in patients with moderate to severe ulcerative colitis 1 year after diagnosis: Results from the MOSAIK cohort in Korea
Authors: PARK Y , Cheon J H , Park Y S , Huh K C , Shin J E , Cha J M , Kim Y S , Eun C S , Yoon S M , Park Y S , Ye B D , Seo B , Kim Y 
Published: January 2020

Abstract

Background
As the treatment paradigm of inflammatory bowel disease changes towards patient-centred treatment, it is becoming increasingly important to measure patient-reported outcomes (PROs). We aimed to identify the changes of emotional health and work- or activity-related outcomes one year after the diagnosis of ulcerative colitis (UC) and its predictors in patients enrolled in the moderate-to-severe UC in Korea (MOSAIK) cohort (ClinicalTrials.gov: NCT02229344).

Methods
The MOSAIK cohort is the first nationwide, prospective, inception cohort on moderate-to-severe UC in Korea. Between August 2014 and March 2017, consecutive patients from 30 tertiary hospitals were enrolled. PRO data including hospital anxiety and depression scale (HADS) for emotional health, and work productivity and activity impairment (WPAI) questionnaire for work- or activity-related outcomes, were collected within the first 4 weeks of diagnosis via patient surveys. Wilcoxon-signed rank tests and linear mixed-effects regression models were used for paired comparisons between baseline and 1 year and assessing the predictors of HADS and WPAI.

Results
Of the 368 enrolled patients, 333 eligible patients were analyzed. The mean age at diagnosis was 39 years and 57.7% (192/333) were male. A considerable number of patients had moderate to high (≥11 by HADS) levels of anxiety and depression (16.0% and 20.5%, respectively), and about half of patients had work and activity impairment (45.5% and 45.8%%, respectively) at baseline. After 1 year follow-up, significant reduction of anxiety and depression (mean difference [MD] in HADS score -1.3 for both anxiety and depression, P&lt;0.001), as well as work and activity impairment (MD -24.1% and -22.4%, P&lt;0.001) was noted. Higher disease activity (partial Mayo Score) during a one-year period was a significant predictor of anxiety, depression, work and social activity impairment. Among the symptoms of UC, abdominal pain was a significant predictor of depression and work and activity impairment, and weight loss and diarrhoea were significant predictors of activity impairment.

Conclusion
Newly diagnosed moderate-to-severe UC patients had considerable anxiety, depression, and work and activity impairment at baseline, but significant improvement was noted after 1 year. Controlling symptoms and disease activity was the most important factor to improve PROs after 1 year.
P603 Persistence of vedolizumab maintenance therapy: Findings from a Belgian registry
Authors: Louis E , Muls V , Bossuyt P , Colard A , Nakad A , Baert D , Mana F , Caenepeel P , Vanden Branden S , Vermeire S , D’Heygere F , Strubbe B , Cremer A , Coche J C , Setakhr V , Baert F , Vijverman A , Coenegrachts J L , Flamme F , Hantson A , Wijnen K , Piters E , Dolin P 
Published: January 2020

Abstract

Background
Clinical trials and observational studies have demonstrated the clinical efficacy of vedolizumab (VDZ) as maintenance therapy for Crohn’s disease (CD) and ulcerative colitis (UC). This report presents long-term data on persistence of VDZ maintenance therapy in real-world clinical practice in Belgium.

Methods
The Belgian VDZ Registry (ENCePP EUPAS6469) enrolled 202 VDZ-treated ulcerative colitis (UC) or Crohn’s disease (CD) adult patients (26% with no prior use of anti-TNF therapy) from 19 centres across Belgium. The median length of VDZ therapy prior to enrolment was 11 months. Patients were followed-up every 6 months after enrolment with the assessment of IBD features, use of biologics, and disease activity. Clinical remission was defined as the Harvey–Bradshaw Index (HBI) &lt;5 or partial Mayo Score (pMS) &lt;2. Missing value imputation (last observation carried forward) was used to partially account for missing disease activity scores. If a 6-monthly disease activity score was missing, the disease activity score from the previous 6-monthly assessment was used.

Results
The mean duration of VDZ therapy, including use prior to enrolment, was 31 months, with 68% of CD patients and 75% of UC patients using VDZ therapy for 48 months. Clinical remission rate after 42 months of VDZ therapy was higher in UC (84%) than CD (67%), and higher for patients without prior anti-TNF therapy (87%) than those with prior anti-TNF therapy (70%).
Fifty-seven (29.4%) patients discontinued VDZ during follow-up, due to loss of response (n = 40), adverse event (n = 7), clinical remission (n = 4), pregnancy planning (n = 3), and patient choice (n = 3).

Conclusion
These real-world long-term Belgian data demonstrate a high persistence of VDZ maintenance therapy among both CD and UC patients, with highest clinical remission rates seen in patients with UC and those with no prior anti-TNF therapy.
P604 Can we reduce intravenous monoclonal antibody observation times without compromising patient safety? A single centre retrospective observational study
Authors: REES F , Packham A , Blake C , Hills E , Scutt G , St Clair-Jones A 
Published: January 2020

Abstract

Background
Monoclonal antibodies (MAbs) are integral to inflammatory bowel disease (IBD) management. The administration of intravenous (IV) MAbs, infliximab and vedolizumab, for Brighton and Sussex University Hospital patients is via an outpatient clinic. Licensing specifies lengthy observation times; infliximab for induction (infusion 1 to 3) and maintenance (infusion 4 onwards) requires 1 to 2 h observation. Vedolizumab for induction (infusion 1 to 2) requires 2 h observation and maintenance (infusion 3 onwards) 1-h observation. This can affect waiting times; 33% UK patients waited longer than two weeks for infliximab. A reduction in observation times could improve capacity but needs to be done without compromising patient safety.

Methods
A single centre observational study was conducted. Retrospective data were collected on all current patients receiving infliximab or vedolizumab at BSUH. Data were collected over 12 weeks (April to July 2019); patients seen twice in this period were included once. The presence of reaction from current and previous infusions was determined by patient questioning and patient records review. Reaction occurrence, nature and management were recorded.
There is not a grading system for IBD infusion-related reactions. To standardise we used the cancer Common Terminology Criteria for Adverse Events; grade 3 and above is designated severe (grade 5 being death).

Results
For infliximab 130 patients were reviewed with 2607 infusions administered in total. For vedolizumab 69 patients were reviewed with 557 infusions administered in total.
Due to the small sample size significance could not be reached.
The survival plot indicates high levels of ‘no reactions’ observed in the first 4 infusions of infliximab 97.7% (+1.6%, -4.7%), and first 3 infusions of vedolizumab 96.9% (+2.3%, −8.8%).

Considering capacity over 12 weeks, for infliximab a minimum of 121 could be recouped and 64 h for vedolizumab. Extrapolated this could equate to 740 h per year.

Conclusion
All reactions occurred within three infusions, were non-severe and managed within the infusion clinic. By removing the observation period from infusion 4 onwards, infusion clinic capacity could be increased but further data from multiple centres are required to prove significance.