bluuebunny/crossref_metadata_2025_split huggingface dataset:
P387 Real-world clinical outcomes of biologic-naïve non-complicated Crohn’s disease patients treated with vedolizumab: Results from the EVOLVE study
Authors: Yarur A , Mantzaris G J , Kopylov U , Bassel M , Brett N , Kim H , Lopez C , Saha S , Kifnidi C , Agboton C , Adsul S , Demuth D , Luo M , Wang S , Bressler B 
Published: January 2020

Abstract

Background
Crohn’s disease (CD) can lead to complications that impact treatment (Tx) decisions and its clinical effectiveness. The objective of this analysis was to compare clinical effectiveness outcomes of CD patients treated with first-line biologic vedolizumab (VDZ) who did not have a complicated disease phenotype (non-complicated) to VDZ patients who had complications (complex disease).

Methods
This was a retrospective real-world cohort study of biologic-naïve CD patients (≥18 years old) in Canada, Greece and the USA who initiated VDZ Tx between May 2014 and March 2018. Data were collected from Tx initiation to the earliest of chart abstraction date or death. The non-complicated CD was defined as patients who had mild or moderate disease severity and no active fistula at Tx initiation, had no prior CD-related surgeries since diagnosis and no CD-related hospitalisations within 12 months prior to Tx initiation. The complex disease cohort encompassed all other CD patients. Cumulative rates of clinical effectiveness outcomes over 24 months (Tx persistence, clinical response and clinical remission) were estimated using the Kaplan–Meier method. Using pre-defined hierarchical algorithms, clinical response and clinical remission were assessed from standard disease measures reported in the medical records.

Results
This analysis included 218 CD patients treated with VDZ (non-complicated: 64 (29.3%); complex: 154 (70.6%) from 37 sites. Mean (SD) age at Tx initiation: non-complicated, 46.2 (15.8); complex, 54.0 (16.7); male: non-complicated, 45.3%; complex, 55.2%. Cumulative rates of clinical response were significantly greater in non-complicated than complex disease patients over 24 months (non-complicated: 93.0%, complex: 76.0%, p &lt; 0.01) (Figure 1). Tx persistence (non-complicated: 76.7%, complex: 66.6%, p = 0.68) (Figure 2) and clinical remission (non-complicated: 81.9%, complex: 73.5%, p = 0.36) (Figure 1) were not significantly different between the two cohorts over 24 months. Fewer patients had data for mucosal healing over 24 months, and it was also not significantly different between groups at 12 months (non-complicated: 66.4%, complex: 60.2%, p = 0.95).

Conclusion
A high proportion of patients (70%) had a complex disease when VDZ Tx was initiated but those with non-complicated phenotype had a higher response rate. To help guide physicians in positioning the optimal Tx for biologic-naïve CD patients, it is important to identify the sub-group of patients who can most benefit from VDZ Tx. The results of this real-world study suggest that the biologic-naïve, non-complicated CD patients benefit more from VDZ treatment compared with those with disease complications.
P391 Side-to-side strictureplasty and its modification over the ileocecal valve for extensive Crohn’s ileitis: single-centre long-term outcome
Authors: Bislenghi G , Ferrante M , Sabino J P G , Verstockt B , Martin Perez B , Wolthuis A , Vermeire S , D’hoore A 
Published: January 2020

Abstract

Background
Postoperative recurrence remains a challenging problem in patients with Crohn’s disease (CD). Ileal location and extensive disease are risks factor for surgical recurrence. To avoid short-bowel syndrome, strictureplasty techniques have been proposed. Over the years, the indication for strictureplasty has further expanded to long strictures. We evaluated the long-term effect of side-to-side isoperistaltic strictureplastie (SSIS) (according to the Michelassi technique or modification of this over the ileocecal valve (mSSIS)) and its effect on bowel preservation in CD patients with extensive bowel involvement.

Methods
Fifty-two CD patients with an affected ileal segment (≥ 20 cm) were included (Figure 1). Thirty-day postoperative morbidity was assessed using the comprehensive complication index (CCI). Patients were assessed clinically at 1 and 6 months postoperatively. An ileocolonoscopy and a magnetic resonance enterography were performed 6 months after surgery. Endoscopic disease activity was assessed according to the modified Rutgeerts score (MRS). Perioperative factors related to disease recurrence were evaluated. Clinical recurrence was defined as symptomatic endoscopically (MRS ≥ i2b) or radiologically confirmed stricture/inflammatory lesion requiring initiation/escalation of the medical treatment or surgery. Surgical recurrence was defined as the need for any surgical intervention within or away from the primary strictureplasty. Endoscopic remission was defined as MRS ≤ i1. Deep remission was defined as the combination of endoscopic remission and the absence of clinical symptoms.

Results
Mean CCI for SSIS was 1.9 (Figure 2). At a median follow-up of 70.8 months (range 9.6–118.8), 19 patients (47.5%) experienced clinical recurrence. Surgical recurrence occurred in seven patients (36.9%). Four patients needed resection of the SSIS. In two patients, a Heineke–Mikulicz strictureplasty was performed at the inlet of the SSIS. The median time to clinical recurrence was 29.3 months (11.4–62.8). The median time to surgical recurrence was 42.9 months (11.9–52.7) (Figure 3). None of the perioperative variables (gender, age at surgery, Montreal classification, smoking habits, former surgery, pre- and postoperative medical therapy, length of SSIS, associated surgery, postoperative complications) correlated with clinical recurrence. At the end of the follow-up, deep remission was reached in nine patients (22.5%).

Conclusion
SSIS is safe, effective and provides durable disease control in patients with extensive CD ileitis. The majority of patients (92.3%) maintain the original SSIS after a median follow-up of 70.8 months. Although not as frequent (15%), endoscopic remission has been observed when an mSSIS has been performed.
P398 The early appearance of anti-drug antibodies during the induction phase predicts the clinical response of adalimumab and infliximab in IBD
Authors: Roblin X , williet N , veyrard P , boschetti G , berger A E , nancey S , flourie B , paul S 
Published: January 2020

Abstract

Background
Several studies have shown a link between circulating anti-TNF levels during induction and clinical progression during IBD. There are less data on the detection of anti-drug antibodies at induction because it requires the use of so-called ‘drug-tolerant’ techniques. The purpose of our study was to investigate in two distinct cohorts (IBD patients on IFX or ADA) whether the early appearance of anti-drug antibodies measured using a drug-tolerant test was associated with clinical progression.

Methods
In a retrospective study, we included all patients followed in our department for at least 3 months and having had an anti-TNF dosage from W2 of induction under ADA or IFX. At follow-up, therapeutic failure was defined by the obligation to optimise, a change in biotherapy, the use of corticosteroids or surgery. IFX and ADA levels were measured routinely (Lisa-Tracker; Theradiag) and anti-medicine antibodies were detected by ‘drug-sensitive’ ELISA technique (Lisa-Tracker; Theradiag) or ‘drug-tolerant’ as previously described [1]. Patients with a positive rheumatoid factor were excluded.

Results
54 patients were included in ADA (mean age: 36 years, sex ratio M/F = 54%, CD: 65%, combotherapy: 10%) and 54 treated with IFX (mean age: 35 years, sex ratio M/F: 46%, CD: 62%, combotherapy: 65%). The search for anti-drug antibodies to W2 using a ‘drug-sensitive’ technique did not reveal any antibodies, whereas 74% of patients on ADA (AAA &gt; or = 2.5 µg/ml eq) and 55% of patients on IFX (ATI &gt; or = 4µg/ml eq). Under ADA, the duration of treatment until loss of response was significantly shorter in the presence of AAA at W2: 6 months vs. 24 months (HR = 18.51; 95CI = 4.35–78.11; p &lt; 0.001). In multivariate analysis, the only independent factor associated with failure was the rate of ADA antibodies to W2 (HR = 18.17; 95CI: 4.27–77.45; p &lt; 0.001). Under IFX, the treatment time to loss of response was significantly shorter in the presence of ATI to W2 (ATI &gt; or = 4µg/ml eq): 5.5 months vs. &gt;24 months (HR = 13.89; 95CI = 4.08–47.31; p &lt; 0.001). In multivariate analysis, the only independent factor associated with failure was the level of anti-IFX antibodies to W2 (&gt; or = 4 µg/ml eq) (HR = 8.07; 95CI: 3.13–20.82; p &lt; 0.001). The higher quartiles of ATI and AAA were significantly associated with poor outcomes (p &lt; 0.001 for each anti-TNF).

Conclusion
The early onset of anti-drug antibodies in the induction phase as early as W2 is the only isolated independent factor associated with loss of response. Anti-drug antibody frequencies are very high when measured with a drug-tolerant test and these Abs may be more neutralising with ADA than with IFX.
P405 Comparison of long-term outcomes of infliximab vs. adalimumab in 1488 biologic-naive Korean patients with Crohn’s disease
Authors: Jung Y S , Han M , Park S , Cheon J H 
Published: January 2020

Abstract

Background
Data on the comparative effectiveness of infliximab (IFX) or adalimumab (ADA) in patients with Crohn’s disease (CD) are rare, particularly for Asian patients. We compared the clinically key outcomes (surgery, hospitalisation, and corticosteroid use) of these two drugs in biologic-naive Korean patients with CD.

Methods
Using National Health Insurance claims, we collected data on patients who were diagnosed with CD and exposed to IFX or ADA between 2010 and 2016.

Results
We included 1488 new users of biologics (1000 IFX users and 488 ADA users). Over a median follow-up of 2.1 years after starting biological therapy, there were no significant differences in the risk of surgery (ADA vs. IFX; adjusted hazard ratio [aHR], 1.30; 95% confidence interval [CI], 0.86–1.95), hospitalisation (aHR, 1.05; 95% CI, 0.84–1.32), and corticosteroid use (aHR, 0.84; 95% CI, 0.58–1.22) between IFX and ADA users. These results were unchanged even when only patients who used biologics for over 6 months were analysed (aHR [95% CI]; surgery: 1.41 [0.88–2.26], hospitalisation: 1.06 [0.83–1.35], and corticosteroid use: 0.82 [0.56–1.21]). Additionally, these results were stable in patients treated with biological monotherapy or combination therapy with immunomodulators.

Conclusion
In this nationwide population-based study, there was no significant difference in the long-term effectiveness of IFX and ADA in the real-world setting of biologic-naive Korean patients with CD. In the absence of trials to directly compare IFX and ADA, our study supports that the choice of one of these two biologics may be allowed to be determined by the preference of patients and/or physicians.
P411 Faecal calprotectin is more tightly associated with endoscopic disease activity compared with other biomarkers in patients with inflammatory bowel disease under maintenance treatment with adalimumab
Authors: Orfanoudaki E , Theodoraki E , Foteinogianopoulou K , Mantaka A , Koutroubakis I 
Published: January 2020

Abstract

Background
Fecal calprotectin (FC) has been suggested as an important biomarker for the management of patients with inflammatory bowel disease (IBD). It is an indirect index of disease activity and plays a crucial role in the treat-to-target strategy. Consecutive measurements of FC in patients in clinical remission can predict a disease relapse and lead to early treatment optimisation. We aimed to compare FC with other biomarkers as for their association with endoscopic activity in IBD patients under maintenance treatment with adalimumab.

Methods
Consecutive IBD patients under maintenance treatment with adalimumab were studied retrospectively based on prospectively recorded data in an IBD registry. Inclusion criteria were at least one available endoscopic evaluation with accompanied biomarkers measurement within the last ± 3 months in the study period (10/2016–9/2019). Biomarkers assessed were FC (home testing Βühlmann fCAL ELISA), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), haemoglobin (Hb), white blood cells (WBC) and platelets (PLT). The disease was considered as active if endoscopic Mayo score was ≥2 in ulcerative colitis (UC) and SES-CD score &gt;6 for Crohn’s disease (CD).

Results
From a total of 72 IBD patients under maintenance treatment with adalimumab, 53 met inclusion criteria [49 CD, 32 men, mean age 42.3 ± 14.9 years, mean disease duration 13.4 ± 9.5, median adalimumab use 34 (23–65) months, combination with immunosuppressants 11 (22%)]. In the logistic regression analysis with dependent variable, the endoscopic active disease FC (mean value 470.8 ± 382.3μg/g) and ESR were independently significantly correlated with the endoscopic disease activity (OR:1.002 95% CI 1.001–1006, p = 0.003 and OR:1.05 95% CI 0.01–1010, p = 0.01 respectively). FC identified patients with endoscopic active disease with an area under the receiver operating characteristic curve (AUC) value of 0.78 (95% CI 0.64–0.88) higher than the other biomarkers [CRP, AUC 0.70 95% CI 0.56–0.82; Hb, AUC 0.55 95% CI 0.41–0.69; ESR, AUC 0.57 95% CI 0.43–0.71; PLT, AUC 0.56 95% CI 0.42–0.69 and WBC, AUC 0.43 95% CI 0.35–0.63). In the pairwise comparison of the ROC curves, there was a significant difference of the AUC of FC and the AUC of Hb, ESR, PLT and WBC (all with p &lt; 0.05). There was no significant difference between the AUC of FC and that of CRP (p = 0.35). FC levels &gt;413 μg/g had a sensitivity of 75% and a specificity of 76% in predicting endoscopic active disease.

Conclusion
These real-life results indicate that in IBD patients under maintenance treatment with adalimumab faecal calprotectin home testing performs better than the other biomarkers in predicting the disease endoscopic activity.
P414 Risk factors for the development of anti-drug antibodies to infliximab and adalimumab in Crohn’s disease
Authors: Khoo E , Lord A , Hanigan K , Croft A , Radford-Smith G 
Published: January 2020

Abstract

Background
Anti-tumor necrosis factor-α (anti-TNFa) therapy have been established as an effective maintenance treatment for complicated Crohn’s Disease (CD). However, the efficacy of Infliximab (IFX) and Adalimumab (ADM) may be affected by low serum levels and/or the presence of anti-drug antibodies (ADA). This reinforces the importance of therapeutic drug monitoring (TDM). We aim to assess the clinical benefit of proactive vs. reactive TDM. Secondly, to assess the impact of TDM on clinical management. Thirdly, to identify risk factors for low serum drug levels and the development of ADA in CD patients.

Methods
This was a single-centred observational cohort study performed at a tertiary hospital, comprising of total 229 CD patients: 142 received IFX and 87 received ADM, who have had a trough drug level, tested using enzyme-linked immunosorbent assay. Demographic and clinical data were retrospectively collected from electronic medical records. Fisher’s Exact Test was used to determine if there are nonrandom associations between variables. A p-value of less than 0.05 was considered statistically significant.

Results
One hundred and fourteen patients (49%) receiving a standard anti-TNFa regimen had subtherapeutic drug levels (67 had IFX &lt; 3 μg/ml and 47 had ADM &lt; 5 μg/ml). Interestingly, almost half of this cohort were asymptomatic. Reactive TDM completed among symptomatic patients have shown to have a statistically significant benefit in detecting subtherapeutic drug level (p = 0.0001). Following these results, only fifty-two patients (46%) had a change of therapy (29 IFX, 25 ADM); while the remaining sixty-two patients (54%) continued the same dosing regimen with only one documented admission within 90-days following the drug level being taken. Eight patients (4%) were found to have positive ADA, all in the presence of subtherapeutic drug levels. Two of these had a subsequent flare of their disease. They were all switched to another class of biologic therapy. Non-smoking status at diagnosis and the concomitant use of immunomodulator were found to have statistically significant associations with a therapeutic drug level (p = 0.0176 and p = 0.0001, respectively). Similarly, both of these risk factors were associated with lower risk of ADA formation (p = 0.0057 and p = 0.0165, respectively).

Conclusion
This study suggests that a large proportion of patients have subtherapeutic drug levels at standard dosing schedules. However, low drug levels do not correlate with a higher risk of complications if patients are in clinical remission. The results of this study also indicate that non-smoking status at diagnosis and the concomitant use of immunomodulator are associated with higher serum drug levels and lower risk of developing anti-drug antibodies.
P428 Oral mesalamine use in Crohn’s disease after implementation of the American College of Gastroenterology guidelines: a TARGET-IBD cohort study
Authors: Gupta N , Sands B E , Regueiro M , Dubinsky M , Rubin D , Hanson J , Aberra F , Weiss M , Watkins S , Gazis D , Long M 
Published: January 2020

Abstract

Background
American College of Gastroenterology (ACG) guidelines for the management of adults with Crohn’s disease (CD) in March 2018 state that oral mesalamine, ‘should not be used…to treat CD.’ 1 This abstract estimates the prevalence of any use of mesalamine among patients with CD before and after the implementation of the guideline. It also aims to describe current utilisation patterns of mesalamine in CD by disease phenotype, location, and concomitant use of biologic agents.

Methods
TARGET-IBD is a longitudinal cohort of IBD patients receiving usual care in the USA; this abstract includes CD patients enrolled between March 2017 and December 2018. Medication use was captured as any use in the follow-up period. Use of mesalamine was stratified into patients who were on mesalamine alone or patients on mesalamine and a biologic. The proportion of patients on mesalamine was estimated in time windows after the policy change to discern penetration into usual practice.

Results
732 patients from TARGET-IBD who had baseline data prior to the new recommendation were included. Of these, 14% used mesalamine only, 8% used mesalamine plus a biologic, and 78% did not use mesalamine. A total of 65% received care in academic centres and the median duration of disease at enrolment was 12 years. The distribution of patient characteristics was similar after the policy change. Six months after the ACG recommendation, 11% of patients used mesalamine only, 7% of patients were on mesalamine plus a biologic, and 82% did not use mesalamine. Prevalence of use for the 3 and 6 month time windows was similar. Subsequent therapy changes and additions in patients on mesalamine are shown in Figure 1. Location (colon vs. ileum) and type of CD (inflammatory vs. fistulising) were statistically significant predictors of the odds of any mesalamine use both before and after the policy change (OR 3.233 (CI 1.725–6.061) and 3.334 (CI 1.931–5.755, respectively)).

Conclusion
Mesalamine use remained stable in the TARGET-IBD CD population, despite the release of the ACG guideline. Individuals with colonic, inflammatory disease were more likely to receive mesalamine, as were Medicare recipients. There was little difference between academic and community practice in implementation of the new standards. Given that the guidelines are relatively new, it is important to follow these participants over a longer period and monitor practice differences and ways to reinforce the practice recommendations to improve the quality and cost of care.
P431 Vitamin D binding protein in the limelight: IBD-related inflammation and circulating levels of vitamin D binding protein, total, free and bioavailable 25-hydroxyvitamin D
Authors: Aksan A , Böttger K , Hein N , Caicedo-Zea Y , Diehl I , Schumann C , Armbruster F P , Stein J M 
Published: January 2020

Abstract

Background
Vitamin D deficiency occurs frequently in patients with Crohn’s disease (CD) and ulcerative colitis (UC). While recent cohort studies support an association of vitamin D with important clinical parameters and outcomes in IBD, the complex interplay of inflammation with vitamin D metabolism in IBD poses a viscious circle. We sought to further illucidate the relation between inflammation and different vitamin D parameters. To the best our knowledge, this was the first study to focus on the relationship between vitamin D binding protein (VDBP), circulating total, free, and bioavailable 25-hydroxyvitamin D (25(OH)D), and inflammation, in adult IBD patients.

Methods
This was a comparative, single-centred, cross-sectional study in patients with IBD aged 18–65 years. Full blood count, transferrin, albumin and hsCRP were determined by standard methods. The presence/absence of inflammation was assessed based on serum hsCRP levels (cutoff &lt;5mg/l). VDBP levels were determined by ELISA, and 25(OH)D by LCMS. Free and bioavailable vitamin D levels were calculated using the validated formula. IBM SPSS version 25.0 was used for statistical analysis.

Results
In total, 129 subjects with IBD (70 male/59 female; 82 CD/47 UC; mean age 41.7 ± 12.6 years) were enrolled. Of these, 38/129 had inflammation (19 m/19 f; 26 CD/12 UC; 39.6 ± 12.9 years) while 91/129 had no inflammation (40 m/51 f; 56 CD/35 UC; 42.5 ± 12.5 years). Subjects with disease activity had significantly higher leukocyte, erythrocyte sedimentation rate (ESR) and hsCRP, but lower transferrin, transferrin saturation (TSAT) and albumin levels than those without inflammation (p &lt; 0.05). Average serum levels of 25(OH)D (24.6[6.8–54.8] vs. 26.4[5.0–74.4]ng/ml), free 25(OH)D (5.9[1.3–13.3] vs. 1.0[1.0–21.4]ng/ml) and bioavailable 25(OH)D(2.3 [0.1–4.7] vs. 2.4[0.5–19.5]ng/ml) were similar in patients with vs. without inflammation (p &gt; 0.05). However, VDBP levels were significantly higher in inflammatory conditions (359.6[252.2–530.6] mg/l vs. 327.4[183.5–560.3]mg/l; p &lt; 0.05) and showed a positive correlation with CRP levels (0.293, p &lt; 0.001). Ratio of free/total 25(OH)D correlated negatively with CRP levels (−0.282, p = 0.002).

Conclusion
High levels of circulating VDBP were associated with inflammatory activity. Moreover, free/total 25(OH)D ratio was inversely associated with inflammation. Other vitamin D parameters including total, free and bioavailable 25(OH)D showed no association with inflammation. These findings suggest that VDBP may play a bigger role than thought as a modulator of vitamin D and inflammation, and that simultaneous detection and investigation of plasma VDBP may provide additional insights into this complex interaction.