bluuebunny/crossref_metadata_2025_split huggingface dataset:
P454 Serum oncostatin M predicts mucosal healing in Crohn’s disease patients treated with infliximab
Authors: Bertani L , Antonioli L , Fornili M , Fornai M , Tapete G , Albano E , Baiano Svizzero G , Ceccarelli L , Mumolo M G , Baglietto L , Marchi S , Blandizzi C , Costa F 
Published: January 2020

Abstract

Background
A number of Crohn’s Disease (CD) patients fail to respond to infliximab (IFX) treatment. For this reason, the identification of a biomarker suitable to predict treatment outcome represents one of the most intriguing challenges for gastroenterologists. Oncostatin M (OSM) is a member of the interleukin 6 cytokine family, which is upregulated significantly in CD inflamed intestinal mucosa. OSM has been suggested as a promising biomarker to predict the responsiveness to anti-TNF therapy in patients with inflammatory bowel diseases. The aim of the present study was to evaluate the suitability of the evaluation of OSM serum levels as a predictive marker of treatment response to IFX.

Methods
We included CD patients treated with IFX during 2017 and 2018. All patients underwent a colonoscopy at week 54, when treatment response was evaluated in terms of mucosal healing (MH, defined as disappearance of ulcers). At baseline and after 14 weeks of treatment, OSM was evaluated by ELISA on serum samples collected before drug infusion. We assessed also faecal calprotectin (FC) at baseline and week 14. Mann-Whitney test was used to evaluate the correlation between OSM and FC levels at baseline and week 14 with MH at week 54. Spearman correlation between OSM and FC values at baseline and week 14 was computed as well. Logistic regression models to predict MH at week 54 were carried out by the Akaike Information Criterion (AIC) and Area Under the Curve (AUC).

Results
In a cohort of 45 patients (24 males) included in the study, 27 displayed MH. At baseline, OSM levels were significantly lower in treatment responders than non-responders (p &lt; 0.001). Similar results were obtained at week 14, when FC levels also were lower in responders than non-responders (p &lt; 0.001 for both OSM and FC). OSM values at baseline and week 14 were significantly associated (Spearman correlation = 0.92, p &lt; 0.001). The diagnostic accuracy of binary OSM at baseline in predicting MH (AIC = 26, AUC = 0.93) was greater than that of binary FC at week 14 (AIC = 34.7, AUC = 0.89).

Conclusion
These preliminary data suggest that OSM and FC are able to predict the outcome of treatment with IFX. Of note, at variance with FC, the predictive capability of OSM was appreciable at baseline, thus allowing to propose OSM as a promising biomarker for driving therapeutic choices in Crohn’s disease patients.
P456 Longer-term outcomes in acute severe colitis
Authors: CAMPBELL R , Haddock R , Parman K , MacDonald J , Seenan J P 
Published: January 2020

Abstract

Background
Acute severe ulcerative colitis (ASUC) is a medical emergency. Rescue medical therapy is increasingly used in steroid-refractory patients but has historically been considered to delay rather than prevent colectomy. We have previously described short-term outcomes from our unit of cases of ASUC, as defined by Truelove and Witt’s criteria, over a 1 year period (July 2016 to June 2017). Data on longer-term outcomes is now available.

Methods
Electronic patient records (EPRs) of cases included in the original study were reviewed. Outcomes including readmission rates, need for colectomy, steroid use, medical escalation and rates of biochemical remission (as defined by faecal Calprotectin (FC) &lt;250μg/l) were recorded.

Results
In total, 58 cases (51 patients) were included in original cohort. 19 failed initial medical therapy with steroids with 10 successfully treated using rescue medical therapy thus avoiding colectomy. Only 1/10 required subsequent colectomy during our median follow-up period of 32 months.
29/51 (56.9%) patients settled with steroids alone. 3 died of unrelated causes so were excluded from further analysis. Further oral steroids were prescribed in 53.8% (14/26).
6 patients were already receiving an immunomodulator (azathioprine or mercaptopurine) prior to initial presentation. 75% of the remainder (15/20) were discharged on aminosalicylates as their only maintenance therapy but the majority (60%, 9/15) subsequently required medical escalation with only 30% (6/20) continuing aminosalicylate monotherapy. 1 colectomy also occurred in this group.
17 readmissions occurred in 12 patients with the majority (52.9%, 9/17) within 1 year. At the end of follow-up two out of three patients (66.7%, 12/18) were considered to be in biochemical remission (FC &lt;250 μg/l).

Conclusion
Rescue medical therapy for ASUC provides sustained benefit with the vast majority avoiding delayed colectomy. Patients admitted with ASUC have significant readmission rates, particularly within 1 year with frequent need for further steroids and/or escalation of medical therapy. Long-term remission rates are high but aminosalicylate monotherapy is rarely adequate to achieve this. All patients with an adequate response to treatment for ASUC should be considered for initiation of immunomodulator and/or biologic Rx prior to discharge. ASUC patients should be considered for more intensive follow-up and early, aggressive medical escalation. An enhanced inpatient liaison service and early review clinic is planned to support this.
P458 Association between adalimumab serum levels and level of remission in Crohn’s disease
Authors: Hambli S , Rogeau S , Duveau N , Nachury M , Branche J , Gérard R , Wils P , Lauriot Dit Prevost C , Lambin T , Desreumaux P , Labalette M , Pariente B 
Published: January 2020

Abstract

Background
Adalimumab (ADA) is effective as induction and maintenance therapy in Crohn’s disease (CD). Serum ADA levels have been shown to be correlated with clinical remission. Therapeutic goals have evolved based on the notion of ‘treat to target’ and the aim is to achieve deep remission. The objective of this study was to consider the association between serum ADA levels and clinical, biological, endoscopic and iconographic remission in CD.

Methods
From October 1, 2016 to December 31, 2018, all CD patients receiving ADA who had a serum ADA level test with anti-ADA antibodies (AAA) detection were consecutively included. We compared serum ADA levels between the following groups: patients with and without clinical remission, patients with biological remission and those with a CRP &gt;5mg/l, patients with endoscopic remission and those with ulcerations and patients with iconographic remission and those with active radiological lesions. In addition, we defined optimal cut-off values to reach these therapeutic targets by analysing ROC curves.

Results
Three hudred and four patients were included corresponding to a total of 445 assays. Indications for the ADA assay were mainly for persistent disease activity in 308 (69%) samples. An immunosuppressant was initially associated with ADA treatment in 154 (35%) samples and 75 (17%) assays were performed under combotherapy. ADA concentrations were higher in patients who started ADA in combotherapy (8.3 vs. 6.6 μg/ml, p = 0.005), but not in patients treated by combotherapy at the time of dosing (8.7 vs. 7.1 μg/ml, p = 0.12). Serum levels of ADA were significantly higher in patients in remission compared with patients with active disease for clinical remission (7.9 vs. 6.3 μg/ml, p = 0.015), biological remission (9.5 vs. 5.1 μg/ml, p &lt;0.001), endoscopic remission (10.1 vs. 6.1 μg/ml, p &lt;0.001) and luminal iconographic remission (9.1 vs. 6.8 μg/ml, p = 0.04). ROC curves and the areas under the curve (ASC) were analysed to determine optimal cut-off values of serum ADA levels to predict these different levels of remission: 6.45 μg/ml (AUC 0, 56, p = 0.027) for clinical remission, 7.35 μg/ml (AUC 0.67, p &lt; 0.001) for biological remission, 9.75 μg/ml (AUC 0.64, p = 0.002) for endoscopic remission and 7.80 μg/ml (AUC 0.58, p = 0.04) for luminal iconographic remission.

Conclusion
High levels of ADA are associated with clinical, biological, endoscopic and iconographic remission in CD. Optimal cut-off values of ADA have been identified and increase as deep remission is obtained. These results suggest that serum ADA levels should be considered to be one of the tools in the tight control strategy of CD and adapted according to pre-defined objectives (clinical, biological or mucosal).
P483 Vedolizumab serum drug levels are not associated with clinical outcomes or markers of disease activity in inflammatory bowel disease
Authors: Shields S , Seenan J P , Nowell E , Dunlop A , Galloway P , Macdonald J 
Published: January 2020

Abstract

Background
Treatment options in Inflammatory Bowel Disease (IBD) include anti-TNFα and anti-integrin biologics. Therapeutic drug monitoring (TDM) is used to support clinical decision making and improve treatment outcomes with anti-TNFα drugs infliximab and adalimumab.1,2 It is unclear if TDM can offer similar benefits with vedolizumab (VDZ) and there are no clinical guidelines for using TDM with VDZ3. The aim of this study was to identify if drug levels (DL) are associated with clinical outcomes and markers of disease activity in patients treated with VDZ.

Methods
All VDZ DLs performed since introduction of testing at our unit in December 2018 were retrospectively identified. Target DLs of &gt;30 μg/ml during induction (≤14 weeks since treatment initiation (TI)) and &gt;10 μg/ml in maintenance (&gt;14 weeks after TI) were agreed based on available published data. Dose information, timing of DL, lab results and disease activity scores were obtained from electronic patient records and paired with the DL dose. Calprotectin was included if recorded within 3 months of DL. Patients were classified as in remission or mild, moderate or severe active disease according to partial Mayo Score for ulcerative colitis and Harvey–Bradshaw Index for Crohn’s disease. Sub-analysis was undertaken according to timing of testing in relation to TI.

Results
Sixty pre-dose trough VDZ levels were identified from 41 patients. Median VDZ level was 25.7 μg/ml (&lt;3.5–&gt;70). Median time from TI to first VDL DL was 36 weeks (4.6–184). No relationship was identified between VDZ levels and biochemical markers of disease (Figure 1). Fourteen (23.3%) TDM were performed during induction. 6/14(42.8%) had subtherapeutic DLs; 3 in remission, 1 mild, 2 severe disease. The remaining 8/14(57.1%) had therapeutic DL; 3 mild, 3 moderate, 1 severe disease, 1 unknown. Forty-six (76.7%) TDM were performed during maintenance. Five out of 46(10.9%) had subtherapeutic DLs; 3 remission, 1 moderate disease, 1 unknown. The remaining 41/46(89.1%) had therapeutic DLs; 16 remission, 11 mild, 10 moderate, 3 severe disease, 1 unknown. For both sub-analysis groups, no relationship between disease state and drug level was observed.

Conclusion
The results from this small cohort do not suggest a relationship between serum VDZ levels and clinical outcomes. Further research in larger cohorts is needed to confirm or refute these findings.

References
P495 Usefulness of a capsule endoscopy scoring system in understanding the disease state of Crohn’s disease
Authors: Omori T , Kambayashi H , Murasugi S , Ito A , Yonezawa M , Tokushige K 
Published: January 2020

Abstract

Background
Crohn’s disease (CD) is a pathological condition that develops because of inflammatory and organic changes such as stenosis. The Lewis Score (LS) and Capsule Endoscopy Crohn’s Disease Activity Index (CECDAI) are employed for scoring small bowel lesions in CD using small bowel capsule endoscopy (SBCE). However, it remains unclear whether the obtained score can contribute to the understanding of the disease state or the selection of treatment. This study aimed to examine whether the existing scoring systems (LS and CECDAI) and the new Crohn’s Disease Activity in Capsule Endoscopy (CDACE) scoring system proposed by us were useful in understanding the disease state of CD.

Methods
After obtaining the results of intestinal patency evaluations using patency capsules from June 2012 to June 2018, 196 times (108 CD patients) who underwent SBCE were included in this retrospective study. The cut-off values of LS, CECDAI, and CDACE were calculated using the receiver operating characteristic curve to determine the extent of small intestinal lesions and the presence or absence of stenotic lesions. Using the cut-off values, the sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) of each scoring system were determined. In CDACE, the small bowel is divided into quartiles, and the degree of inflammation (range: 0–4) for each quantile (range: 0–16) (inflammation score: A), number of quartiles with inflammation (range: 0–4) (range score: B), and degree of stenosis (range: 0–3) (stenosis score: C) were scored; the CDACE score was calculated as follows: A × 100 + B × 10 + C (score range: 0–1643).

Results
For LS, the Se, Sp, PPV, and NPV were 83.7%, 73.5%, 75.9%, and 81.8%, respectively, for inflammation in multiple quantiles (2/3 quantiles or more) (cut-off value: 10) and 94.9%, 90.5%, 71.2%, and 98.6%, respectively, with regard to the presence or absence of stenosis (cut-off value: 196). For CECDAI, the Se, Sp, PPV, and NPV were 93.8%, 86.1%, 82.6%, and 93.4%, respectively, for multiple quantiles (both proximal and distal) (cut-off value: 5) and 51.3%, 87.9%, 51.3%, and 87.9%, respectively, with regard to the presence or absence of stenosis (cut-off value: 11). For CDACE, the Se, Sp, PPV, and NPV were 100%, 82.4%, 78.6%, and 100%, respectively, for multiple quantiles (multiple locations excluding two consecutive zones) (cut-off value: 320) and presence or absence of stenosis was identified in the first digit.

Conclusion
CECDAI was more likely to predict the extent of inflammation than LS, although it was difficult to determine the presence or absence of stenosis. Based on the scores, CDACE may be a useful scoring system in clinical practice where the disease state of CD needs to be determined.
P516 Daily consumers of drip-filtered coffee have a decreased risk of developing late-onset Crohn’s disease
Authors: Widbom L , Hultdin J , Ekblom K , Karling P , Nilsson L M 
Published: January 2020

Abstract

Background
Coffee is known to impact on colon motility, alter gut-related immune response, and to affect symptoms among inflammatory bowel disease (IBD) patients. In spite of this, the role of coffee as a determinant of IBD is unclear. The aim of this study was to investigate how coffee correlates to the risk of developing late-onset IBD in general, and subdivided into Crohn’s disease and ulcerative colitis.

Methods
This nested case-control study within the large, population-based Northern Sweden Health and Disease Study (NSHDS), included data from 78 patients with IBD and 311 controls matched for age, sex, time and area of sample collection. Cases were included in NSHDS at least one year prior to IBD diagnosis. Coffee consumption was assessed by questionnaire-data, differing between drip-filtered and boiled unfiltered coffee. Risk associations were estimated through conditional logistic regressions.

Results
Results differed between different subgroups of IBD and coffee. Our main finding was a decreased risk of Crohn’s disease in subjects with a daily intake of drip-filtered coffee in comparison with subjects with a less frequent intake (Table). After adjustments for smoking, body-mass-index, educational level and marital status the results remained. Adjusted OR for Crohn’s disease was 0.22; 95% CI 0.07–0.76

Conclusion
Our results indicate potential biochemical differences depending on coffee preparation technique on IBD risk, with possible implications for prevention or treatment. Further studies are warranted.
P547 Inadequate vitamin C status and association with inflammatory biomarkers in adults with active Crohn’s disease
Authors: Wall C , MacFarlane K , Carr A , Day A , Gearry R 
Published: January 2020

Abstract

Background
Micronutrient deficiencies are common in inflammatory bowel disease (IBD) due to the inflammatory burden and changes in dietary intake. Vitamin C, an essential water-soluble antioxidant required for tissue repair and immune function, is found primarily in fresh fruit and vegetables however, this food group is more often avoided by people with IBD compared with the general population. This research aimed to determine serum vitamin C status in subjects with active Crohn’s disease, measure urinary vitamin C excretion in healthy controls (HC) and Crohn’s disease patients before and after exclusive enteral nutrition (EEN) and assess associations between inflammatory markers and vitamin C.

Methods
Stored serum and random urine samples prospectively collected from adults with mild to moderately active Crohn’s disease and adult HC were analysed. Both HC and Crohn’s disease groups received EEN with a known vitamin C content for two weeks. Serum and urinary vitamin C were measured using high-performance liquid chromatography with electrochemical detection. Urinary vitamin C was standardised to urinary creatinine. Non-parametric t-tests and correlations were performed.

Results
EEN was initiated in 38 patients (aged 16 to 39 years old). Inadequate serum vitamin C (&lt;50 µmol/l) was present in 36/38 patients with active Crohn’s disease and 45% had hypovitaminosis C. Baseline C-reactive protein (CRP) was 12 mg/l (range, 3 to 158 mg/l) and faecal calprotectin was 1065 µg/g (range, 60 to 3838 µg/g). Serum vitamin C correlated weakly with CRP (r = −0.30 95% CI: −0.58 to 0.03, p = 0.06) but not with faecal calprotectin. Two weeks of EEN was completed by 30 (79%) patients and 17 (81%) HC. The average vitamin C intake was 168mg/day (range, 108–252 mg/day). Baseline urinary excretion of vitamin C was low in both Crohn’s disease and HC. Following EEN urinary vitamin C excretion increased significantly in both groups (Figure 1).

Conclusion
Patients with active Crohn’s disease had inadequate vitamin C status. EEN increased urinary vitamin C excretion in both Crohn’s disease and HC, suggesting low baseline dietary vitamin C intake and potentially enhanced utilisation. Further research with a larger patient cohort would provide a greater understanding of vitamin C metabolism in active Crohn’s disease.
P548 Efficacy, safety, and pharmacokinetics after switching from infliximab originator to biosimilar SB2 in inflammatory bowel disease patients: A long-term observational, prospective cohort study
Authors: Fischer S , Mesfin S , Klenske E , Schmitt H , Vitali F , Hirschmann S , Ramming A , Zundler S , Rath T , Krebs S , Dörje F , Uter W , Nagore D , Meyer S , Neurath M F , Atreya R 
Published: January 2020

Abstract

Background
SB2 is a biosimilar infliximab approved for the treatment of inflammatory bowel disease (IBD) patients. These are the first prospective data investigating long-term efficacy, safety, and pharmacokinetics after switching from infliximab originator to biosimilar SB2 in IBD patients.

Methods
This is a prospective, observational cohort study of patients that underwent a switch from infliximab originator to biosimilar SB2 in 2017 as part of routine care at the outpatient Clinic for IBD at the University Hospital of Erlangen, Germany. Long-term safety and clinical effectiveness were recorded over a follow-up period of 18-months. Clinical disease activity was assessed by the Harvey–Bradshaw Index (HBI) in Crohn’s disease (CD) and the partial Mayo Score (pMS) in ulcerative colitis (UC) patients. C-reactive protein (CRP) was analyzed at every patient visit, and IFX trough-level (TL) and anti-IFX antibodies (ADA) were measured prior to every SB2 administration, using the Promonitor® tests. The occurrence of adverse events was registered at every patient visit.

Results
A total of 148 IBD patients (96 CD, 52 UC) was enrolled. The median duration of previous infliximab treatment before the switch was 29 months (range 1.0–110.0). Median disease activity in CD was an HBI of 3 (0–16) at switch (baseline), 2 (0–13) at month 6, 3 (0–15) at month 12 and 2.5 (0–11) at month 18. Median disease activity in UC was a pMS of 0 (0–6) at baseline, 1 (0–4) at month 6, 1 (0–4) at month 12 and 1 (0–5) at month 18. The median TL for all IBD patients was 6.3 mg/ml (0.1–33.7) at baseline, 5.0 mg/ml (0.1–34.3) at month 6, 6.3 mg/ml (0.1–35.8) at month 12 and 5.1 mg/ml (0.1–35.4) at month 18. CRP for all IBD patients was 2.2 mg/l (0.1–45.6) at baseline, 2.2 mg/l (0.1–90.4) at month 6, 2.3 mg/l (0.1–169.5) at month 12 and 2.7 mg/l (0.1–19.8) at month 18. In the 18-month follow-up period, 12/103 (11.7%) of patients who were ADA-negative at baseline developed ADA post-switch. Altogether, 40 (27%) IBD patients discontinued SB2 treatment during the 18-month follow-up period (4 anaphylaxis, 20 loss of response, 7 non-serious and 9 serious adverse events), 2 paused during pregnancy, 1 discontinued in clinical remission, 10 were lost to follow-up (7 change of physician, 3 unknown). Serious adverse events comprised 3 malignancies (breast and prostate carcinoma, neuroendocrine malignancy), 1 liver abscess and 5 intestinal surgical procedures (1 perforation, 1 ileus, and 3 stenoses).

Conclusion
Switching from IFX originator to biosimilar SB2 was not associated with an increase in disease activity. No clinically meaningful changes in IFX trough levels or immunogenicity were identified. Altogether, SB2 was well tolerated in a real-life setting.