bluuebunny/crossref_metadata_2025 huggingface dataset:
P484 Effectiveness and safety of ustekinumab in patients with Crohn’s disease: a real-world experience
Authors: Mohammad D , Alshahrani A , Bao Y , Alramdan R , Rajani A , Chauhan U , Salena B , Tse F , Greenwald E , Albashir S , Halder S , Armstrong D , Marshall J , Narula N
Published: January 2020

Background

Ustekinumab is a monoclonal antibody against the p40 subunit of IL-12 and IL23 which has been proven efficacious and safe in clinical trials, yet, real-word effectiveness studies are lacking. We aimed to determine the effectiveness and safety of ustekinumab in Crohn’s disease patients in a usual care setting, as well as to identify factors that predict response to treatment.

Methods

This was a retrospective review of patients with Crohn’s disease who had received ustekinumab at McMaster University Medical Center between January 2017 and August 2019. The primary endpoints were 12-month rates of clinical response, clinical remission and endoscopic improvement (according to physician assessment). We also performed a multivariate logistic regression to determine independent predictors of treatment effectiveness. Key safety outcomes were rates of adverse events including infections.

Results

We included 123 patients with Crohn’s disease, 58.8% of which had ileocolonic disease. Of these patients, 79.5% had prior TNF-antagonist exposure and 17.1% had previously used vedolizumab. The 12-month rate of clinical response, clinical remission, and endoscopic improvement, were 88%, 35%, and 47% respectively. On univariable analyses, longer disease duration was associated with a lower likelihood of achieving endoscopic improvement (OR 0.91 per year of disease duration, 95% CI 0.84–0.99, p = 0.03). On multivariate logistic regression, concomitant steroid use (OR 0.34, 95% CI 0.12–0.99, p = 0.049) and previous vedolizumab exposure (OR 0.13, 95% 0.02–0.77) were significantly associated with less likelihood of achieving clinical response at 12 months. Adverse events occurred in 13% of patients and infections occurred in only 1% of patients.

Conclusion

Ustekinumab has been effective in our real-world experience at achieving clinical response, clinical remission and endoscopic improvement in patients with Crohn’s disease. We found that concomitant steroid use and prior vedolizumab exposure were associated with a lower likelihood of clinical response. Further prospective data are needed to understand whether these are truly predictors of lack of response, or represent confounding from patients with more refractory disease.
P488 How reliable is the online medical information on paediatric inflammatory bowel diseases?
Authors: Velasco Rodríguez-Belvís M , Palomino Pérez L M , Sánchez Fernández-Bravo C , Sanchiz Perea A , Jose Luis L F , Domínguez Ortega G , Cañedo Villarroya E , Pedrón Giner C C , Jorge M P , Rodríguez Manchón S , Muñoz González A , Muñoz Codoceo R A
Published: January 2020

Background

Patients with paediatric Inflammatory Bowel Diseases (p-IBD) and their families widely use the Internet as a resource and tend to read the first page of 10 results. However, online content may be of questionable quality, and valuable information may be hard to find. This study aimed to (i) determine the average quality of online information on p-IBD and (ii) analyze whether it depends on the source of information.

Methods

A google search was performed on the 28 October 2019 using the keywords: ‘Crohn’s disease’, ‘ulcerative colitis’, ‘Inflammatory Bowel Disease’, ‘colonoscopy’, ‘endoscopy’, all of them combined with the terms ‘paediatric’ and ‘children’. We recorded the first 10 results for each search and excluded scientific papers, advertisements, videos and sites requiring subscription. Websites were classified according to their origin as hospital, professional society, government agency, health press or patient organisations. The quality of the information was assessed with the DISCERN instrument, a validated 16-point questionnaire (total score 16–80) to evaluate the quality of written information. DISCERN scores were graded as excellent (68–80), good (55–67), fair (42–54), poor (29–41) or very poor (16–28). In order to minimise subjectivity, four evaluators assessed the quality, and the mean total score was calculated for every selected website. The proportion of websites with excellent or good grading in each category was compared using the Fisher test.

Results

We identified 100 websites and 65 met the inclusion criteria. The type of authorship and DISCERN scores are shown in Table 1. The overall median DISCERN score was 40.8 [interquartile range, IQR 10.5]. Only 5 websites had an excellent or good score. The proportion of websites with excellent or good grading was significantly higher in those from government agencies and professional societies (33.3% and 30% vs. 2% and 0%, p < 0.05). None of the health press websites showed excellent or good grading. Surprisingly, no websites from patient organisations were identified.

Conclusion

The quality of online information on p-IBD is highly variable. Most of the easily found websites are from hospitals, but professional societies and government agencies provide a higher quality of information. Improvement of online information on p-IBD is still needed.
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

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 < 0.001) and fCal (776 μg/g at baseline, 305 μg/g at 1 year, medians, p < 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

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 (<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 < 80 cm and 27.3% (n = 24) of men had < 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 <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 >41%. According to DXA measurements, 25.6% (n = 11) of men had total body fat <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 >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 < 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 < 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

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 (>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

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

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

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

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 <150µg/ml and/or PCR<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 < 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

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 < 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

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 < 0.0001) than non-remitters. In univariate logistic regression, predictors of no endoscopic remission were a high endoscopic activity at baseline (eMs > 2, OR 0.2 IC 95% 0.05–0.86, p = 0,021; UCEIS > 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 < 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.
P539 Assessment of age as a risk factor for adverse events in patients from the tofacitinib ulcerative colitis clinical programme
Authors: Lichtenstein G R , Bressler B , Vermeire S , Francisconi C , Lawendy N , Shi H , Salese L , Judd D , Loftus E V
Published: January 2020

Background

Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of UC. Safety and efficacy of tofacitinib were demonstrated in Phase (P)2/3 induction studies, a 52-week, P3 maintenance study, and are being further investigated in an ongoing, open-label, long-term extension (OLE) study.1,2 Here, we provide an updated analysis of age as a risk factor for adverse events (AEs) in the tofacitinib UC clinical programme.3

Methods

Proportions of AEs and serious AEs (SAEs), and incidence rates (IRs; unique patients with events per 100 patient-years) for AEs of special interest (AESIs), were determined for two cohorts: the Maintenance Cohort (patients who received placebo or tofacitinib 5 or 10 mg twice daily [BID] in the maintenance study) and the Overall Cohort (all tofacitinib 5 or 10 mg BID-treated patients in the P2/P3/OLE studies; as of May 2019), stratified by age. Multivariable Cox proportional hazards regression analyses were performed to assess whether older age was associated with increased risk of AESIs in the Overall Cohort.

Results

In the Maintenance Cohort, IRs of AEs and SAEs were generally similar between treatment groups, with no age-related trend in the proportions of AEs in tofacitinib-treated patients. AESIs were infrequent in both treatment groups; however, herpes zoster (HZ; non-serious and serious) IRs were numerically higher in the ≥40 to <50 and ≥50 years age groups for patients treated with tofacitinib 10 mg BID vs. placebo and tofacitinib 10 vs. 5 mg BID. In the Overall Cohort, IR of serious infections was generally similar between age groups, while IRs of opportunistic infections (OIs) and HZ (non-serious and serious), malignancy (excl. non-melanoma skin cancer [NMSC]), NMSC and major adverse cardiovascular events increased with increasing age. The IRs of HZ and NMSC were significantly greater in patients ≥50 years compared with patients <30 years, and in patients ≥30 to <40 years for NMSC. In multivariate analyses, older age was identified as a significant predictor of malignancy (excl. NMSC), NMSC and HZ.

Conclusion

In the Overall Cohort, there was a trend for an increase in the rates of OIs, HZ, malignancy (excl. NMSC) and NMSC with increasing age. In multivariate analyses, older age was associated with increased risk of malignancy (excl. NMSC), NMSC and HZ. The results of this analysis are generally consistent with previous studies suggesting older age may be associated with an increased risk of certain AESIs in patients with UC, and in some instances in the general population.4

References
P540 GB004, a novel prolyl hydroxylase inhibitor for inflammatory bowel disease, leads to gut-targeted HIF-1α pathway engagement in a multiple-dose study in healthy subjects
Authors: Levesque B , Taylor Meadows K , Buch A , Flynn M , Peters K , Olson A , Shen J , Slee D , Van Biene C , Aranda R , Vande Casteele N , Opiteck G
Published: January 2020

Background

GB004 is a small-molecule prolyl hydroxylase inhibitor that stabilises hypoxia-inducible factors (HIF-1α), key transcription factors involved in the protective cellular responses at the intersection of hypoxia and inflammation. GB004 was selected based on its gut-targeted profile to limit systemic on-target effects associated with HIF-1α stabilisation. GB004 is in clinical development for the treatment of inflammatory bowel disease and was shown to be safe in a single ascending dose study. The study described here evaluates the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of multiple daily doses of GB004 in plasma and colon biopsies.

Methods

This was a randomised, double-blind, placebo-controlled, multiple-dose, Phase 1a study conducted in healthy subjects at a single site in Canada. Three dose levels of GB004 or placebo formulated as a solution were administered orally once a day for 8 days; safety and PK were evaluated. Colon biopsies were obtained one day prior to the first dose and on Day 8. Colonic tissue concentrations of GB004 and HIF pathway target genes were determined.

Results

Forty-two subjects (20 male and 22 female) were dosed. No serious adverse events or deaths were recorded. The most commonly observed adverse event in GB004-treated subjects was dizziness (31%,10/32); all events were mild and did not result in study drug discontinuation. There were no identified risks of GB004. Following oral dosing, GB004 was rapidly absorbed and eliminated from the systemic circulation, with a median time to maximum concentration of 0.5 h for all dose levels. Concentrations of GB004 measured in colon biopsies were greater than in plasma at the time of the biopsy. Dose-related HIF pathway target gene engagement and PD were confirmed.

Conclusion

This study demonstrated that multiple daily doses of GB004 solution were safe and tolerable. The PK profile was consistent with its intended preferential exposure in the gut. A clinical study of GB004 is ongoing in patients with ulcerative colitis to explore safety, tolerability, PK and PD both systemically and within colonic tissue (NCT03860896). A tablet formulation is also being developed.
P541 Are we addressing the top ten research priorities in IBD?
Authors: Geldof J , LeBlanc J F , Lucaciu L , Segal J P , Lees C W , Hart A
Published: January 2020

Background

In 2016, the top 10 research priorities in treatment of inflammatory bowel diseases (IBD) were outlined by a group of clinicians, patients and patient-support organisations based in the UK, using the infrastructure of the James Lind Alliance (JLA) Priority Setting Partnership. Priority statements were ranked in order of perceived importance. The aim of this study was to measure the current distribution of these research priorities in European-led IBD clinical trials, ongoing or completed within the last 3 years, in light of the JLA recommendation. Pharmaceutical-led trials were excluded given the inherent bias towards drug conception and approval.

Methods

The database from Clinicaltrials.gov and European Union Clinical Trials Register were used to create an overview of non-pharmaceutical-driven European clinical studies involving adult patients with IBD. Trials posted on 09/08/2016 (publication date of the top 10 research questions) up to 16/11/2019 were included. The list was completed by trials found to be relevant, although not retrieved initially, based on author consensus.

Results

In total, 154 European non-pharmaceutical-funded clinical studies were found, of which 112 addressed one of the outlined top 10 IBD-research priorities and 8 addressed multiple topics simultaneously. Almost a third (30%) investigated the optimal treatment strategy considering efficacy, safety and cost-effectiveness (immunomodulators, biologics, surgery) in IBD (Priority 1). Development or assessment of biomarkers for stratification of patients (Priority 2) was the subject of 29 studies (24.2%). Twenty-one (17.5%) studies focused on altering gut microbiota (Priority 10). Eleven or fewer studies focused on fatigue, IBD-related pain and perianal Crohn’s disease (Priorities 4, 5 and 8). Priorities 3 and 7 concerning the role of diet in IBD management were evaluated in 9.2% studies. A minority of studies, 2.5% and 1.7%, respectively, addressed optimal timing for surgery in terminal ileal Crohn’s disease (Priority 9) and the best treatment for diarrhoea/incontinence (Priority 6). Of all 19 European countries, France, the UK and Spain accounted for almost half of all reviewed studies (49.2%).

Conclusion

Since publication of the top 10 research priorities in IBD treatment, non-pharmaceutical-funded research has mostly been focusing on development and validation of new therapeutic strategies, investigation of biomarkers and the role of gut microbiota. The latter topic has gained significant interest in IBD research, more so than higher-ranked Priority statements 3 to 9. Further research should prioritise the potential benefit of dietary interventions and patient-reported outcomes, such as management of IBD-related pain, fatigue and faecal incontinence.
P545 Deep remission assessed by endoscopy, magnetic resonance or intestinal ultrasound, in refractory Crohn’s disease patients in clinical remission with ustekinumab: a real-life single-centre experience
Authors: Calvo Moya M I , Omella Usieto I , González Lama Y , Matallana Royo V , González Partida I , Menchen Viso B , De Lucas Téllez de Meneses R , González Rodriguez M , Bella del Castillo P , Vera Mendoza M I
Published: January 2020

Background

Current therapeutic goals in Crohn’s disease (CD) include not only the mere absence of symptoms but also the objective resolution of macroscopic lesions, so-called deep remission (DR), which has been related to better outcomes. DR is usually acknowledged by endoscopy, although magnetic resonance (MR) or intestinal ultrasound (IUS) are also reliable, provide extramucosal information and may be more appropriate in certain clinical scenarios. Data regarding the achievement of DR with ustekinumab in real-life clinical practice is still scarce.

Methods

Retrospective cohort study carried out in a tertiary hospital between April 2017 and April 2019 including patients who had clinically active CD (Harvey–Bradshaw index [HBI] ≥ 4) objectively assessed by either endoscopy, MR or IUS; received intravenous induction with ustekinumab, had achieved clinical remission and had treatment response assessed by either endoscopy, MR or IUS. DR was deﬁned by SES-CD 0–3 or Rutgeerts index i0 if endoscopically assessed, or by complete normalisation of inﬂammatory parameters on cross-sectional imaging. Endoscopic response was deﬁned by the decrease of SES-CD of 50% compared with baseline. Radiographic response was deﬁned by improvement in bowel wall thickness, inﬂammatory fat, mural blood ﬂow and hyperenhancement compared with baseline imaging by physician global assessment. Demographics, clinical data and information regarding ustekinumab treatment were collected.

Results

90 patients treated with ustekinumab at our centre were analyzed, but only 28 met inclusion criteria (14(50%) female; median age 45 (43–50)) with a median follow-up of 19 (IQR: 15–23) months. All of them had previously failed to antiTNFα and 20 (71%) failed to ≥2 biologics. Treatment response assessment was made by endoscopy (22 cases; 79%) or cross-sectional imaging technique (6 cases; 21%) in a median time of 10 months (IQR: 7–13) from the start of treatment. Deep remission was achieved in 18 (64%) patients. Endoscopic response was achieved in 5 (18%) additional patients. Five (18%) remaining patients obtained no objective response to ustekinumab despite being in clinical remission. Patients who had received prior treatment with ≥2 biologics or those classified as B2 or B3 according to Montreal Classification were less likely to achieve deep remission, although those associations did not reach statistical significance.

Conclusion

In our experience, a majority of refractory CD patients who achieved clinical remission with ustekinumab also reached deep remission assessed by either endoscopy, MR or IUS.
P546 Ileal ulcer size significantly impacts the ability to achieve endoscopic remission: a post-hoc analysis from the SONIC trial
Authors: Narula N , Wong E , Achuthan A , Dulai P , Colombel J F , Marshall J K , Ferrante M , Reinisch W
Published: January 2020

Background

Endoscopic remission (ER) is an important target of treatment for Crohn’s disease (CD). However, it is unclear how individual baseline endoscopic characteristics impact the ability to achieve ER. We aimed to determine endoscopic prognostic factors that influence the likelihood of achieving ER in CD.

Methods

This was a post-hoc analysis of SONIC (NCT00094458; YODA #2019–3980), where data from 172 patients who had endoscopic scores at baseline and at week 26 were evaluated. Individual components of the Crohn’s Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score for Crohn’s disease (SES-CD) indices were used to evaluate the impact of baseline ulcer depth (CDEIS) and size (SES-CD) on likelihood of achieving ER at week 26. Ileum and colon segments were evaluated separately. Multivariate logistic regression models were used to evaluate the relationship between baseline endoscopic findings and achievement of ER in each segment at week 26, after accounting for known confounders including disease duration and treatment allocation. Results are presented as odds ratios (OR) with 95% confidence intervals (CI).

Results

The rate of ulcer improvement in the ileum was significantly lower than rates of healing throughout the colon (p < 0.0001) (see figure). Patients with ulcer size >2 cm in the ileum were less likely to achieve ER of the ileum compared with patients with ulcer size <2 cm (OR 0.31, 95% CI 0.11–0.89, p = 0.03). Ulcer size did not consistently impact likelihood of achieving week 26 ER in colonic segments. Patients with ileal ulcer size > 2 cm that were also deep were less likely to achieve ileal ER, when compared with patients with smaller or superficial ulcers (OR 0.10, 95% CI 0.02–0.68, p = 0.02). High baseline SES-CD score (>16) or CDEIS score (>12) did not impact the likelihood of achieving week 26 ER.

Conclusion

Ulcer size and depth, but not the overall degree of endoscopic inflammation, seem to impact likelihood of achieving week 26 ER. ER may be more difficult to achieve for patients with larger and deep ulcers in the ileum. These findings may have implications for recruitment into clinical trials and would support the importance of balancing these prognostic factors in trial arms. Further prospective data are needed to validate these findings.
P551 Combination therapy in IBD Patients: Do we need to maximise the dose of Azathioprine?
Authors: Arieira C , Dias de Castro F , Cúrdia Gonçalves T , Moreira M J , Cotter J
Published: January 2020

Background

The use of combination therapy of anti-TNF and thiopurines in inflammatory bowel disease (IBD) is associated with greater efficacy and lower immunogenicity. However, the dose of thiopurine in this setting remains to be elucidated. The aim of the study was to compare the trough levels, anti-TNF antibodies and the inflammatory biomarkers between two groups in combotherapy: one with low dose (LDA) and one with standard dose (SDA) of azathioprine.

Methods

A retrospective study was performed, selecting all patients with an established diagnosis of IBD, who were on combined maintenance treatment (at least 6 months of therapy) with azathioprine and anti-TNF. We divided the population into two groups according to the azathioprine dose: LDA <2 mg/kg and SDA: ≥ 2 mg/kg).

Results

We included 99 patients, 52.5% female with a median age of 33 (17–61) years. Eighty patients (80.8%) were diagnosed with Crohn’s Disease and 19 (19.2%) with ulcerative colitis. Seventy-one (71.8%) patients were on infliximab (IFX) and 28 (28.3%) were on adalimumab (ADA). In the IFX group, there were no differences between trough levels (6.86 vs. 6.70 mg/ml, p = 0.892) or formation of antibodies anti-IFX (6.3% vs. 5.1%; p = 0.838) in SDA vs. LDA. Moreover, there were no differences between inflammatory biomarkers: CRP (p = 0.315) and faecal calprotectin (p = 0.48) among the two groups. Regarding ADA group, there were no differences in trough levels of ADA (10.15 vs. 10.65 mg/ml, p = 0.836), the formation of antibodies anti-ADA (7.7% vs. 6.7%; p = 0.916) and in inflammatory biomarkers: CRP (p = 0.525) and faecal calprotectin (p = 0.496) among the two groups.

Conclusion

In our cohort, there were no differences between anti-TNF trough levels, formation of antibodies anti-TNF and in inflammatory biomarkers among patients in combotherapy with azathioprine in a standard dose vs. lower dose. In terms of immunogenicity, lower doses of azathioprine seem sufficient to inhibit the formation of antibodies, with better tolerance and better safety profile.
P557 Increased risk of anastomotic leak in Crohn’s disease patients unable to complete preoperative mechanical bowel preparation
Authors: Iesalnieks I , Marek F , Kala Z , Kunovsky L
Published: January 2020

Background

To assess the risk of postoperative anastomotic leak in Crohn’s disease patients unable to complete the preoperative mechanical bowel preparation (MBP): a prospective observational study from two referral centres in Germany and the Czech Republic.

Methods

Preoperative MBP was used routinely in all Crohn’s disease patients undergoing elective ileocolic or colorectal resections completed by the formation of an anastomosis since 6/2016. The MBP consisted of 2 L Polyethyleneglycol (PEG) solution combined with two doses of oral antibiotics Metronidazole and Paromomycin. The MBP was defined as incomplete when patients were not able to drink the whole amount of PEG solution due to side effects or complications. The primary endpoint was occurrence of anastomotic leak. The secondary endpoint was the incidence of postoperative intraabdominal septic complications (IASC) which were defined as an anastomotic leak, intraabdominal abscess or fistula and peritonitis.

Results

Between 6/2016 and 11/2019, 96 Crohn’s disease patients underwent elective ileocolic or colorectal resections after receiving preoperative MBP and oral antibiotics. Twenty-four (25%) developed complications of MBP, mostly vomiting; 17 patients (18%) were not able to complete MBP. The presence of extraintestinal disease manifestations (Hazard Ratio 4.8, p = 0.029), preoperative weight loss (HR 5.7, p = 0.019) and female sex (HR 13.3, p = 0.005) were associated with an increased probability not to be able to complete MBP. Postoperative anastomotic leak occurred in 2 patients (2%). The risk of anastomotic leak was significantly higher in patients unable to complete MBP (12%) as compared with patients with complete MBP (0%, p = 0.03). Postoperative IASC occurred in 7 patients (7%). Patient unable to complete preoperative MBP were at higher risk to develop IASC; however, the difference was not statistically significant (18% vs. 5%, p = 0.10)

Conclusion

The anastomotic leak rate is very low when preoperative mechanical bowel preparation and oral antibiotics have been used. However, patients not able to complete MBP might be at an increased risk.