bluuebunny/crossref_metadata_2025_split huggingface dataset:
P499 Objectively assessed disease activity during ustekinumab treatment in a nationwide real-life Crohn’s disease cohort
Authors: af Björkesten C G , Ilus T , Hallinen T , Soini E , Eberl A , Hakala K , Heikura M , Hirsi E , Jussila A , Kellokumpu M , Koskela R , Koskinen I , Moilanen V , Nielsen C , Nieminen U , Nuutinen H , Heikkinen M , Suhonen U M , Tillonen J , Utriainen K , Vihriälä I , Wennerström C , Borsi A , Nissinen R , Koivunen M , Sipponen T 
Published: January 2020

Abstract

Background
Real-life long-term evidence on ustekinumab treatment response in patients with Crohn’s disease (CD) is scarce. We performed a retrospective non-interventional nationwide chart review study of dosing and long-term clinical outcomes in Finnish CD patients treated with ustekinumab (FINUSTE2, EUPAS30920).

Methods
FINUSTE2 involved 17 Finnish centres. Eligible patients were adults with CD, receiving an intravenous first dose of ustekinumab during 2017 or 2018. Disease activity data, such as C-reactive protein (CRP), faecal calprotectin (fCal), and the Simple Endoscopic Score for Crohn’s disease (SES-CD) were collected at baseline, 16 weeks, and one year from treatment initiation. A local gastroenterologist at each centre collected the data from health records in an electronic standardised health questionnaire.

Results
One hundred and fofty-five patients (48% female) with a mean age of 44 and disease duration of 14 years initiated ustekinumab treatment for CD. Table 1 summarises patient characteristics at baseline. After induction consisting of one intravenous dose and one to two subcutaneous doses at 8 to 16 weeks, 140 patients (93%) continued to maintenance treatment with subcutaneous ustekinumab. Of 93 patients with a follow-up of at least one year, 77 were still on ustekinumab. During ustekinumab treatment, SES-CD (10 at baseline, 3 at 1 year, medians, p = 0.033) and CRP (7 mg/l at baseline, 5 mg/l at 1 year, medians, p &lt; 0.001) and fCal (776 μg/g at baseline, 305 μg/g at 1 year, medians, p &lt; 0.001) decreased significantly in those patients with data available. Figure 1 describes changes in fCal levels over time.

Conclusion
In this nationwide real-life long-term follow-up study, covering all major centres in Finland, ustekinumab treatment of patients with highly refractory and long-standing CD effectively reduced inflammatory activity, assessed by endoscopy, CRP, and fCal.
P500 Adiposity among IBD patients
Authors: Bletsa M , Karachaliou A , Kokkotis G , Tsoutska M M , Andoniadi S , Papaconstantinou I , Kontogianni M , Bamias G 
Published: January 2020

Abstract

Background
Inflammatory bowel disease (IBD) has been traditionally associated with malnutrition and increased prevalence of underweight status. Nevertheless, according to recent reports, there appears to be an increase in the percentage of overweight individuals among patients with Crohn’s disease (CD) or ulcerative colitis (UC). In the present study, we aimed to evaluate the body composition of a cohort of Greek patients with IBD.

Methods
We analysed data from 88 patients with IBD (CD:58, UC:30, female: 45). Body mass index (BMI) was calculated and waist circumference (WC) was measured in all participants. Body composition was evaluated with a multi-frequency bioelectrical impedance segmental body composition analyser (BIA) (Tanita MC-780) and with dual-energy X-ray absorptiometry (DXA).

Results
9.1% (n = 8) of patients had low BMI (&lt;18.5), 53.4% (n = 47) normal, 22.7% (n = 20) were overweight and 14.8% (n = 13) obese. No differences were seen between CD vs. UC. Furthermore, 27.3% (n = 24) of women had WC &lt; 80 cm and 27.3% (n = 24) of men had &lt; 94 cm. Referring to % total body fat, as reported by BIA, 46.5% (n = 20) of men and 11.1% (n = 5) of women had total body fat &lt;20%, 46.5% (n = 20) of men and 44.4% (n = 20) of women had 21–30%, 7% (n = 3) of men and 28.9% (n = 13)of women 31–40% and 15.6% (n = 7)of women &gt;41%. According to DXA measurements, 25.6% (n = 11) of men had total body fat &lt;20%, 46.5% (n = 20) of men and 15.6% (n = 7) of women had 21–30%, 25.6% (n = 11) of men and 46.7% (n = 21) of women 31–40% and 2.3% (n = 1) of men and 37.8% (n = 17) of women &gt;41%. There was no significant difference in % total body fat between CD and UC patients in either measurement. We observed a significant difference between the two methods regarding the estimation of % body fat, as BIA measurements were lower than those obtained with DXA (p &lt; 0.001, median = 5.53%, 95% confidence interval = 4.82–6.24%). Nevertheless there was a significant correlation between BIA and DXA measurements in the same individual (r2 = 0.9025, p &lt; 0.001).

Conclusion
We found a large proportion of overweight/obese patients in our IBD cohort. The association with increased WC may imply that the total abdominal fat is increased in such patients. As excessive fat content has been shown to negatively affect IBD patients in multiple ways, our results emphasise the need for better assessment of body composition and dietetic interventions in this population.
P502 Tumour necrosis factor antagonists are superior to anti-integrin and anti-IL-12/23 therapies for preventing postoperative recurrence in adult Crohn’s disease patients requiring postoperative therapy
Authors: Nakamura T , Shah R , Sachs M , Chang S , Hudesman D , Click B , Axelrad J 
Published: January 2020

Abstract

Background
Crohn’s disease (CD) recurrence is common after surgical resection. Prior data have demonstrated that postoperative tumour necrosis factor antagonists (anti-TNF) may reduce recurrence, although little is known about the efficacy of other biologic therapies. The aim of this study was to compare biologic type and timing for preventing postoperative objective recurrence in adult CD patients.

Methods
We performed a retrospective chart review of CD patients who underwent intestinal resection from 2009 to 2019 at two academic medical centres. We tabulated baseline variables against treatment groups based on the type of postoperative biologic (anti-TNF, anti-integrin, anti-IL-12/23) and timing of postoperative biologic initiation (before or after 6 months post-op). Propensity score matching was utilised for treatment groups using baseline variables as predictors. Recurrence was defined by endoscopy (&gt;i2 Rutgeerts’ score) or radiography (active inflammation in neoterminal ileum). Survival analysis was performed to assess risk of recurrence by treatment group and timing of biologic initiation.

Results
One hundred and forty-four patients were included (51% male, 13.2% active smokers, 97.9% stricturing and/or penetrating CD, 41.7% prior resection). The majority of patients received anti-TNF therapy. Adjusting for the propensity scores, fewer patients relapsed under anti-TNF compared with anti-integrin (HR 2.87, 1.04–7.99; p = 0.042) and anti-IL-12/23 (HR 3.51, 1.51–8.14; p = 0.03). There was no significant difference in objective relapse between patients on postoperative anti-TNF and no therapy (HR 0.71, 0.31–1.66; p = 0.44) (Figure 1). More patients relapsed when biologics were started after 6 months postoperatively compared with within 6 months (HR = 0.20, 0.08–0.53; p = 0.001) and never started (HR = 0.26, 0.11–0.59; p = 0.001) (Figure 2).

Conclusion
Among propensity score-adjusted CD patients, initiation of biologics within 6 months and anti-TNF agents were superior in preventing postoperative recurrence among patients receiving postoperative biologic therapy.
P508 Safety and efficacy of combining biological therapies together or with small molecules in patients with inflammatory bowel disease: A retrospective multicentre national observational case series study
Authors: Goessens L , Colombel J F , Outtier A , Ferrante M , Truyens M , Lobaton T , Baert F , Bossuyt P , Cremer A , Macken E , Strubbe B , Rahier J F 
Published: January 2020

Abstract

Background
Few data are available regarding the combination of biological therapies (anti-TNF, anti-integrin, anti-interleukins (IL4, 12/23, 17A, 23)) or with a small molecule in patients with IBD. We here report the safety and efficacy of combining these drugs through a national retrospective multicenter case series.

Methods
Cases were extracted from local databases within the last 3 years. Combined therapy was defined as the concomitant use for a minimum of 1 day of 2 biologics or 1 biologic with a small molecule. Patients’ demographics, disease’ characteristics and types of combined therapies were recorded. Safety was defined as the occurrence of any serious adverse event (SAE): serious infection, opportunistic infection, any hospitalisation, cancer and death, whereas the efficacy of combination was clinically appreciated by physicians.

Results
From 8 centres, 23 combined therapies were observed in 19 IBD patients (74% Crohn’s disease, 21% ulcerative colitis and 5% IBD type unclassified). Median age at combination was 43.0 years ([IQR]: 31.5–59.0). Seventeen patients presented with a minimum of 1 concomitant IMID (ankylosing spondylitis (n = 11), psoriasis or psoriatic arthritis (n = 5) and other conditions (n = 5)). Reasons for starting a combination were active IBD (57%), another active IMID (30%) or both (13%). Anti-TNF and anti-integrin were combined in 11 cases, anti-TNF and anti-ILs in 5, anti-integrin and anti-ILs in 4 and other combinations in 3 (anti-TNF+rituximab+methotrexate; anti-IL4+anti-IL12/23; anti-IL12/23+methotrexate+leflunomide). The median duration of combined therapies was 5 months ([IQR]: 2–9). During 15.8 patients/years of combined therapy, 11 adverse events (AE) including 9 SAE were recorded in 8 patients. Eight infections were reported with various combinations: anti-TNF and anti-IL in 4 cases, anti-TNF and anti-integrin in 3 and anti-TNF+rituximab+methotrexate in 1. Two infections (both anti-TNF+ anti-integrin) were graded severe leading to hospitalisation, 6 were graded mild or moderate. Cancer and death were not observed. After combined therapy, IBD disease activity was clinically improved in 44% and remained stable in 50% of patients, whereas clinical improvement of IMID was observed in 25% of patients. Overall, the combination of treatments was withdrawn due to ineffectiveness or serious adverse events in 39% and 4%, respectively.

Conclusion
In our experience, the combination of biologics in patients with IBD ±. another IMID was associated with short term increased efficacy in almost half of patients but also with a risk of infections in one third. No new safety signals were observed in this difficult to treat patients but extensive data are urgently needed.
P514 Does faecal diversion induce clinical response for Crohn’s disease of the colorectum?
Authors: Lightner A , Buhulaigah H , Zaghiyan K , Vaidya P , Regueiro M , Fleshner P 
Published: January 2020

Abstract

Background
Fecal diversion is now selectively used in cases of medically refractory Crohn’s proctocolitis or advanced perianal disease. The aim of this study was to evaluate the rate of, and clinical factors, associated with the clinical response following faecal diversion in CD.

Methods
A retrospective chart review of adult CD patients undergoing an ileostomy for medically refractory distal disease (proctocolitis, perianal disease, segmental colitis, proctitis) between 2000 and 2019 at two inflammatory bowel disease centres was conducted. The primary outcome was the rate of clinical response; the secondary outcome was to assess factors associated with clinical response to faecal diversion.

Results
The study cohort of 98 patients had a median age of 40 (range, 19–84) years and included 50 females (51%). Median duration of disease was 15 (1–43) years. Indication for surgery was medically refractory proctocolitis and perianal disease (n = 48;49%), perianal disease alone (n = 34;35%), proctocolitis (n = 8;8%), segmental colitis (n = 5;5%), and proctitis alone (n = 3; 3%). Medications used before surgery included corticosteroids (n = 43;44%), immunomodulators (n = 33;34%) and biologics (n = 52;53%). Biologics used included adalimumab (n = 21), infliximab (n = 10, certolizumab (n = 8), vedolizumab (n = 8) and ustekinumab (n = 5). Only 16 (17%) patients were active smokers. Following ileostomy formation, 32 (33%) patients had a clinical response. The association between patient features and clinical response is shown in Table 1. Clinical response to fecal diversion was significantly decreased in the setting of proctocolitis with perianal disease (p = 0.005) and pre-diversion exposure to biologics (p = 0.04).

Conclusion
This largest report in the biologic era of faecal diversion for medically refractory CD proctocolitis or perianal disease showed that only 33% of patients achieved a clinical response. Both biologic uses before faecal diversion and diversion for proctocolitis with perianal disease were associated with a significantly lower clinical response.
P515 Comparability of upadacitinib pharmacokinetics in Japanese and non-Japanese subjects with ulcerative colitis with the extended-release formulation
Authors: Stodtmann S , Friedel A , Zhou W , MOHAMED M E 
Published: January 2020

Abstract

Background
Upadacitinib (UPA), an oral selective JAK1 inhibitor, is being developed for treatment of patients with moderately-to-severely active ulcerative colitis (UC) in addition to several other inflammatory diseases. UPA has shown favourable efficacy and acceptable safety in UC in an 8-week double-blind placebo-controlled dose-ranging Phase 2b induction study in subjects with moderately-to-severely active UC (U-ACHIEVE trial).

Methods
Sparse blood samples were collected from subjects with UC who were enrolled in the U-ACHIEVE trial, which included Japanese and non-Japanese subjects. UPA plasma concentration vs. time after dose were summarised from the U-ACHIEVE trial. Additionally, data from U-ACHIEVE were pooled with data from UPA Phase 1 and other Phase 2 studies across different inflammatory diseases to characterise UPA population pharmacokinetics. The population pharmacokinetic model was used to estimate UPA plasma exposures from extended-release formulation (dose range 7.5 – 45mg QD) in 168 non-Japanese and 28 Japanese subjects with UC in U-ACHIEVE.

Results
UPA plasma exposures were approximately dose proportional over the evaluated dose range in Japanese subjects with UC. Observed dose-normalised plasma concentrations vs. time since the last dose (Figure 1) and dose-normalised model-estimated UPA exposures were comparable (within 25%) between Japanese and non-Japanese subjects with UC (Table 1).

Conclusion
UPA plasma exposures are similar between Japanese and non-Japanese subjects with UC. This is in agreement with prior assessments in healthy subjects and in subjects with RA which demonstrated comparable UPA exposures between Asian and Western subjects.
P520 Association between ustekinumab trough levels and biomarkers in patients with Crohn’s disease
Authors: Nicolás de Prado M I , Iniesta Navalón C , Gomez Espin R , Gil Candel M , Serrano Díaz L , Rentero Redondo L , Martinez Crespo J J 
Published: January 2020

Abstract

Background
Ustekinumab (UTK) is a human immunoglobulin (Ig) G1 kappa monoclonal antibody approved in 2017 for the treatment of Crohn’s Disease (CD). Up until now, there has not been enough evidence of the relationship between ustekinumab trough levels (UTL) and the clinical evolution and biological markers of the disease. Our study aimed to investigate the relationship between UTL and different biomarkers in a real-world setting.

Methods
We performed a retrospective observational study including patients up to 18 years with CD receiving subcutaneous maintenance regimen of 90 mg UTK every 8 weeks and available UTL. Biochemical response and remission were evaluated with faecal calprotectin (FC) and C-Reactive Protein (CRP) levels. The biochemical response was defined as a decrease of 50% or more of FC and/or CRP baseline levels, and biochemical remission as FC level &lt;150µg/ml and/or PCR&lt;0.4 mg/dl. UTL was determined from serum samples collected prior to the injection using a commercially available validated enzyme-linked immunosorbent assay (ELISA). Continuous variables were tested using the Mann–Whitney U-test. Receiver operating characteristic (ROC) curves were used to estimate the cut-off of the UTK trough level; for scoring purposes, we chose a cut-off that would maximise the sum of sensitivity and specificity. A value of p &lt; 0.05 was considered statistically significant. Statistical analysis was performed using SPSS for Windows.

Results
Forty-two patients were included (27 men and 15 female), with an average age of 47.7 years. The average FC levels were 1358,5μg/ml at the beginning of the treatment. In the maintenance period, we observed a biochemical response in 69% of patients, whose UTL were significantly higher than in non-responders (2.25 µg/ml [IQR: 3.08] vs. 0..65 µg/ml [IQR: 1.95]. respectively; p = 0.037). Likewise. 38% of patients achieved biochemical remission (responders 2.125 µg/ml [IQR: 2.25] vs. non-responders 1.5 µg/ml [IQR: 3.26]; p = 0.476). The AUC for predicting biochemical response by means of UTL was 0.703 [CI 95%: 0.529–0.877] (p = 0.037), with sensitivity of 51%, specificity of 76% and a cut-off of 2.20 μg/ml.

Conclusion
There is limited data on the association between UTL and patient outcome. Our study demonstrates the association between improvement of different biomarkers and higher levels of UTL, with a significant statistic result for biochemical response and non-significant statistic result for biochemical remission, maybe due to a small sample, but with a positive trend. Further studies are necessary in order to conclude that UTL is significant in the management and evolution of the disease and to determinate the optimal cut-off.
P528 Response to biologic therapy in operated Crohn’s disease patients
Authors: Georgieva A C , Atanassova A , Mirchev M 
Published: January 2020

Abstract

Background
About 70% of Crohn’s disease (CD) patients undergo surgery due to disease complication. According to the ECCO consensus, in such cases, the tumour necrosis factor-α (TNF-α) antagonists are a means of choice to prevent post-operative relapse.

Methods
The aim is to evaluate endoscopic, clinical and biochemical outcomes in CD patients, who have undergone surgery, in the course of the subsequent treatment with anti-TNFα mono/combination therapy—anti-TNFα + AZA. Among patients with CD who are undergoing biological treatment, we performed a retrospective analysis of the data of those who underwent surgical intervention associated with Crohn’s disease and subsequently started biological therapy.

Results
Of the 69 CD patients on biological therapy, surgical intervention was performed in 44.92% (n = 31) of cases prior to the initiation of the treatment. The prevalence of patients with right-sided hemicolectomy with subsequent ileotransverse anastomosis was 54.80%, followed by incision and abscess cavity drainage 22.6%, fistula excision 19.4% and left-sided hemicolectomy 3.2%. In 22 patients (71.0%) there was a clinical response (CDAI decline ≤ 100 points), with 66.66% of them achieving clinical remission (CDAI ≥ 150) (p = 0.001, strong correlation r = 0.596, p = 0.001). During the course of treatment, 23.80% lost clinical response after 18 months of treatment. We compared the mean value of the faecal calprotectin (FCP) before starting, and during the course of the biological treatment, we found that the FCP values decreased 1.5 times: 516.78 ± 273.93, (range 100 – 857)/330.46 ± 432.25, (range 5.32–1800). The activity of the disease measured by CDAI decreases twice during the course of the biological treatment: CDAI 378.00 ± 92.89 (range 258–695)/177.93 ± 116.38 (range 34–414) and CRP values decrease over four times: CRP 59.65 ± 64.52 (range 0.9–225)/13.14 ± 23.59 (range 0.13–116.10). During the course of the biological treatment, intestinal complications were observed in 33.33%, and 9.67% of the patients who had both progression and presence of intestinal complications had a subsequent surgery. In 33.33% of cases, the treatment was intensified. 16.70% of them had to switch to another biological drug. Perianal disease prior to biological treatment in operated patients is twice as common (x2 = 3.82, p = 0.050), which in turn appears to be a risk factor for surgical treatment (OR = 3.47 (0.953–12.685)).

Conclusion
In the follow up of the relationship between the occurrence of a clinical response and the onset of biological therapy, we found that the time interval was essential. The earlier the anti-TNFα therapy begins, the greater the likelihood of achieving a clinical and biochemical response (r = 0.326, p &lt; 0.05).
P532 Measuring endoscopic activity in patients treated with vedolizumab for ulcerative colitis
Authors: EMONT C , Gay C , Parmentier A L , Koch S , Ambregna S , Claudé G , Sage P , Zhong P , Briot C , Vuitton L 
Published: January 2020

Abstract

Background
Vedolizumab (VDZ) has proven its efficacy in ulcerative colitis (UC). The delay to obtain endoscopic remission with anti-α4β7 integrin is unclear. We aimed to assess the potential of VDZ to induce endoscopic remission and its characteristics in real-life settings.

Methods
We conducted a pooled analysis with prospective and retrospective data of patients who started VDZ for an active UC in two French hospitals. Patients underwent proctosigmoidoscopies at baseline and at weeks 14, 30 and 54 in the prospective cohort. A central blinded review of all endoscopy recordings was performed by two experts, pooled with some recordings from anti-TNFɑ treated patients. The primary endpoint was the proportion of patients in endoscopic remission (endoscopic Mayo score (eMs) ≤ 1) within 54 weeks. Secondary endpoints included the description of the pattern of mucosal healing and the evolution of UC activity. Characteristics of endoscopic remitters and non-remitters were compared and predictive factors of endoscopic remission were reported in univariate logistic regression.

Results
Forty-two patients were enrolled, 22 in the prospective cohort and 20 in the retrospective cohort. At baseline, 38 (90.5%) patients had previously experienced anti-TNFɑ, 14 (33.3%) were treated with corticosteroids and 15 (35.7%) with immunosuppressors. Twenty-six (61.9%) patients achieved endoscopic remission after a median time of 14 weeks. Endoscopic response and histologic remission occurred in 27 (64.3%) and 21 (50%) patients within 54 weeks, respectively. No specific pattern of mucosal healing was found with VDZ as compared with anti-TNFɑ treated patients. UC activity steady improved over time. Endoscopic remitters had a lower disease activity at baseline (total Mayo score (tMs) 8.1 vs. 9.5, p = 0.007; UCEIS 4.3 vs. 5.6, p = 0.0005; Nancy’s score 2.8 vs. 3.6, p = 0.004) and at week 14 (tMs 3 vs. 6, p = 0.001; eMs 1.3 vs. 2.5, p = 0.005; UCEIS 2.7 vs. 5.4, p = 0.0007; Nancy’s score 2.2 vs. 3.6, p = 0.001) and needed less treatment optimisation (11.5 vs. 81.3%, p &lt; 0.0001) than non-remitters. In univariate logistic regression, predictors of no endoscopic remission were a high endoscopic activity at baseline (eMs &gt; 2, OR 0.2 IC 95% 0.05–0.86, p = 0,021; UCEIS &gt; 5 OR 0.22 IC 95% 0.06–0.84, p = 0.022) and treatment optimisation (OR 0.03; IC 95% 0.01–0.17, p &lt; 0.001).

Conclusion
In our series, about two-thirds of UC refractory patients achieved endoscopic remission during the first year. Endoscopic healing was early reported, in half of patients at the end of the first trimester, actually suggesting a rather fast mechanism of action of VDZ on mucosal healing. Baseline UC activity impacted endoscopic remission.