bluuebunny/crossref_metadata_2025 huggingface dataset:
P621 Physician preferences for biologics (originator vs. biosimilar) for the treatment of ulcerative colitis in France, Germany and the UK
Authors: Huynh L , Hass S , Sands B E , Duh M S , Sipsma H , Cheng M , Lax A , NAG A
Published: January 2020

Background

Although originator biologics are effective therapies for patients with ulcerative colitis (UC), they can be costly and may not be widely available. Therefore, less expensive biosimilars have been developed and approved to treat and manage symptoms. In this new treatment landscape, UC-treatment preferences are unknown. Thus, this interim analysis aimed to characterise physician preferences for biologics for the treatment of UC in France, Germany and the UK.

Methods

As part of a broader chart review study, treatment preferences were also collected from participating gastroenterologists and general practitioners (GPs) in France, Germany and the UK who had treated patients (≥ 18 years) with moderate-to-severe UC who had received ≥ 1 UC-related biologic any time from 2014 to 25 October 2019. Descriptive statistics were used to describe the sample overall, and by physician speciality and treatment preference.

Results

Physicians (161 gastroenterologists; 57 GPs) were from different clinical settings in France (39.9%), Germany (28.4%) and the UK (31.7%). Overall, infliximab (33.0%) and adalimumab (32.1%) were selected more often as first treatment options than their biosimilars (17.0% and 9.6%, respectively). Gastroenterologists preferred biosimilars more frequently than GPs did (35.4% vs. 1.8%). More physicians who preferred biosimilars were from France (48.3%) than Germany (17.2%) or the UK (34.5%). In France and the UK, 93.8% of physicians who selected biosimilars worked in hospital settings; in Germany, 50.0% worked in clinics and 50.0% worked in practice settings with statutory and private patients. Physicians who preferred biosimilars treated more patients with UC in the preceding 12 months than those who preferred originators did (mean ± SD: 110.3 ± 113.9 vs. 94.0 ± 93.2). Although most physicians reported efficacy as a reason for biologic preference (93.6%), physicians who preferred originators were more likely to report good tolerability (73.8%) and patient preference (20.6%) and less likely to report affordability or availability (11.9%) than physicians who preferred biosimilars (63.8%, 10.3% and 44.8%, respectively). In patients who failed anti-TNF therapy, vedolizumab was the preferred treatment (78.9%), although this preference differed by speciality (gastroenterologists: 83.2%; GPs: 66.7%).

Conclusion

Originator biologics for treating patients with moderate-to-severe UC dominate the treatment landscape in Europe, driven primarily by efficacy, tolerability and patient preference. However, variations and differences in preferences by speciality and clinical setting may suggest a need to explore additional treatment options to manage disease symptoms among patients with UC.
P626 Patients with IBD seek extra supportive care: insights from Israeli social media networks
Authors: SHARVIT G , Goren I , Godny L , Yadgar K , Elial Fatal S , Barkan R , Turner D , Dotan I , Yanai H
Published: January 2020

Background

Social Media (SM) networks are a major communication tool for patients with inflammatory bowel diseases (IBD) and healthcare professionals (HCPs). In Israel there are several SM platforms, some guided by HCPs while others are patients closed members groups. The largest HCP- patients network is called ‘Camoni’ (‘like me’). We aimed to assess topics of patients’ interest by exploration through SM.

Methods

This study had two phases: I –a qualitative study to assess topics of patients’ interest- screening. Posts of patients with IBD on ‘Camoni’ were evaluated by thematic analysis: identifying patterned meaning, coding based on topic, and categorising major groups. II - an anonymized survey was distributed online through SM networks. The survey was based on the identified topics in the screening, asking the participants to elect and delve only on the five most relevant topics. Satisfaction was assessed by visual analogue scales (VAS) of 0–100 points.

Results

Screening included 2,123 posts published on Camoni between 2014–2019. The analysis revealed 18 different topics (Figure 1). The online survey was launched on November 2019 and had 329 responders: male 47.9%, age 38 years (IQR 29–51), disease duration 10 years (IQR 4–20), active disease 43%, using medications 80.9%: steroids 8.9%, anti-TNFs 31.6%, anti-integrins 9.1%, ustekinumab 4.6%, tofacitinib 2.1%. Crohn’s disease 63.4%, perianal disease 40.8%, extraintestinal manifestations 27%, history of surgery 36.4%, care in hospital outpatient clinics 67.8%. The distribution of satisfaction VAS scores was asymmetric with skewness to the right (Figure 3). Median (IQR) for general satisfaction of the treating physician - 87.5 (73–99), accessibility to HCPs - 77.5 (48.5–92), HCP professionalism 90 (75–99), degree of understanding patients’ concerns 81 (51–96), effectiveness of communication with HCPs 81 (59.7–96). The first five elected-topics of interest were: diet, lifestyle, complementary and alternative medicine, interpretation of medical results, and referral of patients to specialists and reviews (Figure 2). Most responders (85.1%) prefer to be active on an SM network that is guided by HCPs; however,, only 22% of online survey responders were active on Camoni.

Conclusion

Patients with IBD with a significant disease burden are highly satisfied from conventional care. However, patients are still in need for further support and information, perceived as not being addressed in the conventional setting. An operative multidisciplinary setting in routine care, incorporating dietitians, IBD-nurses and HCP’s focusing on alternative and complementary medicine is advised.
P641 An increased baseline mucosal TNF burden linked to adalimumab non-response: opportunities for therapeutic drug monitoring
Authors: Verstockt B , Stylli J , Rahimian P , Rajulapati A , Ehring K , Thomas D , Sabino J , Ferrante M , Singh S , Vermeire S
Published: January 2020

Background

Various studies report robust associations between serum adalimumab (ADM) exposure and therapeutic outcome, which has led to the implementation of reactive therapeutic drug monitoring. As very little is known how serum levels relate to tissue and faecal ADM levels and to tumour necrosis factor (TNF) levels, we measured serum, tissue and faecal drug and TNF, and questioned how all this is linked to the therapeutic efficacy of ADM.

Methods

We prospectively recruited paired serum, mucosal biopsies and stools from 15 patients with ulcerative colitis (UC, n = 8) and Crohn’s disease (CD, n = 7) initiating ADM. All received ADM standard dosage. Samples were collected at baseline and week 8 (UC) or month 6 (CD). Endoscopic remission was defined as a Mayo endoscopic sub-score 0 (UC) or complete absence of ulcerations (CD). ADM levels were measured using a homogeneous immunoassay in which the ADM-TNFα complex is formed and captured. TNFα and IL-6 were quantified using an in-house developed immunoassay. Total tissue protein content was quantified in order to normalise the data.

Results

Pre-treatment tissue TNF and IL6 levels correlated significantly (r = 0.8, p < 0.001) and were lower in ADM remitters (n = 8) in contrast to non-remitters (4.5 vs. 8.6 pg/mg, p = 0.03; 7.1 vs. 122.5 pg/mg, p = 0.05). Pre-treatment faecal TNF was numerically lower in remitters (0.4 vs. 1.0 pg/mg, p = 0.30), but did not correlate with tissue/serum TNF (p = 0.84, p = 0.58). Although ADM did not significantly impact post-exposure serum or faecal TNF and IL6, it did reduce tissue TNF and IL6 (p = 0.02, p = 0.003), both in remitters (median −38.3%, p = 0.04; median −86.0%, p = 0.04) and non-remitters (median −59.5%, p = 0.16; median −84.5%, p = 0.03). Although TNF and IL6 changes did not correlate with ADM exposure or change in calprotectin, the decrease in faecal calprotectin significantly correlated with tissue, but not serum, ADM levels (r = 0.74, p = 0.01). ADM exposure was significantly higher in remitters as compared with non-remitters, both in serum (14.6 vs. 5.9 mg/ml, p = 0.009) and in tissue (53.1 vs. 24.1 ng/mg, p = 0.04). However, serum and tissue ADM levels correlated only moderately (r = 0.5, p = 0.1). Finally, tissue TNF/tissue ADM ratios were significantly higher in non-remitters, both considering pre (p = 0.007) and post TNF (p = 0.03). Faecal loss of ADM could be documented in a single patient only.

Conclusion

Both in tissue and serum ADM exposure was significantly higher in remitters, though tissue and serum ADM exposure did not perfectly correlate. A higher baseline tissue TNF burden was associated with non-response to ADM, and may help in the differentiation to select the appropriate biological in a given patient: no anti-TNF or intensified dosing in patients with a high baseline tissue TNF burden.
P652 Underweight patients with Crohn’s disease and without vitamin D supplementation are at high risk of vitamin D deficiency
Authors: Vranesic Bender D , Domislović V , Brinar M , Ljubas Kelečić D , Karas I , Novosel M , Matašin M , Krznarić Ž
Published: January 2020

Background

Vitamin D deficiency is frequently present in inflammatory bowel disease (IBD) with a higher incidence in Crohn’s disease (CD) than in ulcerative colitis (UC). Given the involvement of the alimentary tract, many factors can contribute to vitamin D deficiency. The aim of the study was to investigate the association of vitamin D deficiency according to body mass index (BMI) in adult patients with IBD.

Methods

A cross-sectional study was conducted on a cohort of 152 IBD patients, 68.1% (n = 104) CD and 31.9% (n = 48) UC. The mean age of the total study population was 37.3±11.8 years and 57.3% (n = 87) were male. All patients were adult, Caucasian and without vitamin D supplementation. Patients were recruited during one year period.

Results

Out of all IBD patients, 60.5% (n = 92) had vitamin D deficiency, 32.2%, (n = 49) insufficiency and 7.2% (n = 11) sufficiency. According to BMI categories there were 12.5% (n = 19) obese patients, 27.6% (n = 42) overweight, 51.3% (n = 78) with normal body weight, and 8.6% (n = 13) underweight. There was a significant difference in vitamin D levels according to different BMI categories in terms of underweight patients having the lowest vitamin D levels; underweight 29.84±11.94 mmol/l, normal 46 ± 20.7 mmol/l, overweight 48±20.1 mmol/l, obese 51±15.3 mmol/l. In addition, there was a significant correlation of vitamin D levels and BMI values (Rho = 0.212, 95% CI 0.069–0.345, p = 0.004), which was more clearly observed in the lower range of BMI values (Figure 1). Male underweight patients had lower levels of vitamin D compared with female patients (26.6 ± 9 vs. 34.7 ± 5.6, p < 0.05). Both patients with CD and UC had significant positive correlation of vitamin D levels and BMI values (UC Rho=0.40, 95% CI 0.16–0.59, p = 0.001, UC Rho = 0.27, 95% CI 0.01–0.05, p = 0.044). However, when comparing vitamin D levels according to phenotype, a significant difference in vitamin D levels was observed in underweight CD (28.4 ± 11.1) comparing to underweight UC patients (40.6 ± 10.6), p < 0.05. In logistic regression analysis, CD phenotype was risk factor for vitamin D deficiency (OR 2.18 95% CI 1.01–4.72, β = 1.22, p = 0.04).

Conclusion

Our results on untreated IBD patients show a high proportion of vitamin D deficiency both in CD and UC, and significant correlation of vitamin D levels and BMI values, especially in the lower range of BMI values. Moreover, underweight CD patients have lower vitamin D levels comparing to UC. This suggests the need for regular vitamin D monitoring and supplementation especially in IBD patients at risk.
P656 Clinical implications of endoscopic submucosal dissection in management of patients with ulcerative colitis-associated dysplasia
Authors: Sakurai T , Nezu R , Okada A , Komeda Y , Nagai T , Masaki S , Yamada M , Takashima K , Kashida H , Kudo M
Published: January 2020

Background

Colectomy has been recommended for patients presenting ulcerative colitis (UC)-associated dysplasia because of the risk of metachronous recurrence. However, it has been recently proposed that endoscopic submucosal dissection (ESD) of dysplasia, combined with subsequent surveillance, may contribute to avoiding colectomy. This study assessed clinical implications of ESD in UC-associated dysplasia.

Methods

We investigated 30 lesions (27 patients) of UC-associated dysplasia/cancer treated with ESD and surgery (15 ESD and 16 surgery) including a patient who underwent surgery following ESD. Among them, paraffin-embedded tissues of 15 lesions (6 cancers, 7 high-grade dysplasia: HGDs, 2 low-grade dysplasia: LGDs) and 11 surrounding mucosae were available and gene mutation analysis was performed. Indications for ESD were determined according to the criteria applied for sporadic colorectal neoplasms that are based on magnifying endoscopy.

Results

The median follow-up duration was 40 months. Three out of 27 patients (11%) developed metastasis. Although no serious complications, local recurrence, or metastasis occurred in 13 patients undergoing ESD, one out of them (7.7%) had metachronous colorectal cancer 3 years after ESD in the rectum, where TP53 mutation and diffuse p53 staining was found at non-dysplastic mucosae. Based on magnifying endoscopy, we underestimated the invasion depth in two cases: in a case of deeply submucosal invasive mucinous cancer, endoscopic ultrasonography exhibited thickening of the submucosal layer exclusively at the lesion.

Conclusion

The proposed indication for ESD in UC-associated dysplasia is that a lesion is well-demarcated and surrounding mucosa is not actively inflamed and does not exhibit diffuse p53 staining. ESD would contribute to advances in the management of UC-associated dysplasia.
P665 Which second-line biologic after anti-TNF failure during Crohn’s disease: Ustekinumab or vedolizumab, a multicentre retrospective study
Authors: Rayer C , Roblin X , Laharie D , Caron B , Flamant M , Dewitte M , Fumery M , Viennot S , Bourreille A , Pariente B , Siproudhis L , Peyrin-Biroulet L , Bouguen G
Published: January 2020

Background

Anti-TNF antibodies treatments are the only first-line reimbursed biologics for Crohn’s disease (CD) in several countries. Recently, Vedolizumab (VDZ) and Ustekinumab (UST) were added to the therapeutic armamentarium for CD refractory to a first anti-TNF antibody. However, studies comparing these two compounds remain unavailable. Our aim was to compare their efficacy in second-line treatment in CD after failure of one TNF antagonist.

Methods

All patients with CD refractory (primary or secondary non-responders) to first anti-TNF treatment and receiving UST or VDZ as a second biologic were included retrospectively in 10 French tertiary centres. The remission and clinical response were assessed at week 14. On the long-term, the cumulative probabilities of being in remission were estimated using the Kaplan–Meier method and the associated factors using a Cox proportional risk model. The drug survival to assess efficacy as well as side effects was assessed by actuarial analysis.

Results

88 patients were included, 50 (57%) females (mean age: 41 ± 15 years), 61 (69%) being treated with UST and 27 (31%) with VDZ. The first anti-TNF was discontinued for primary or secondary non-response in 66 (75%) patients and for side effects in 22 (25%) patients, without any difference between the anti-TNF antibody previously used. Among the 55 patients with endoscopic data at baseline, 55 (98%) had ulceration, a CRP above 5mg/l for 33/71 (46%) patients and a faecal calprotectin > 250 µg/g for the 12 patients tested. At week 14, no difference was observed for clinical response and clinical remission according to the type of treatment: the rate of clinical response and remission were 74% (UST)/58% (VDZ) (p = 0.20) and 33% (UST)/26% (VDZ) (p = 0.56), respectively. The only factor associated with short-term remission was the lack of optimisation prior to anti-TNF discontinuation (p = 0.038) regardless of the type of second-line therapy (UST, p = 0.02; VDZ, p = 0.03). After a mean follow-up of 67 weeks, the cumulative probabilities of being in remission at 6 and 12 months were 16% and 34% for UST and 25% and 44% for VDZ, respectively (p = 0.24 for UST vs. VDZ). The drug survival was higher in the UST group as compared with the VDZ group (HR (UST vs. VDZ) = 2.36 [1.02–5.5], p = 0.04).

Conclusion

Our preliminary results suggest that VDZ and UST have similar efficacy in the short- and long-term response when used as a second-line biologic therapy in CD refractory to a first anti-TNF antibody. These results will be complemented for the congress by the inclusion of additional patients recruited into this registry.
P672 The escalation of therapy or intervention (ETI) calculator for ulcerative colitis: does it have the potential to help outpatient capacity meet demand?
Authors: Walsh A J , Matini L , Kantschuster R , Lepetyukh M , Simadibrata D , Collins G , Wilson J , Hussain M , Tarafdar A , Brain O , Palmer R , Ambrose T , Satsangi J , Travis S P L
Published: January 2020

Background

Demand for outpatient clinic appointments for ulcerative colitis (UC) often exceeds capacity, since spaces are frequently assigned to routine follow-up of patients who are well. Demand might better be managed by targeting appointments for patients in need of therapeutic decisions. The TrueColours UC (TCUC) Escalation of Therapy or Intervention (ETI) calculator is a potential enabling tool.

Methods

TCUC is a web-based programme based on email prompts linked to validated, disease-specific indices. The ETI Calculator was created after logistic regression showed that patient-reported symptoms (Simple Clinical Colitis Activity Index) and quality of life (IBD Control-8) could calculate the probability of therapy escalation or an urgent intervention during an outpatient appointment (OPA, Figure 1). From June 2018 to August 2019, all OPA for 650 patients using TCUC and under standard OPA follow-up were examined. The probability of escalation at each OPA was calculated using the most recent prior SCCAI and IBD-Control scores (within 2 weeks of appointment). Clinic letters were assessed to determine whether treatment escalation or intervention had occurred during the OPA.

Results

Of 650 patients, 236 had a total of 403 OPAs. 210/403 (52%) of these OPAs resulted in no treatment escalation; 159/403 (40%) had escalation and 34/410 (8%) had de-escalation. An ETI calculator threshold set at 5% estimated probability of treatment escalation would have correctly identified 143/159 (90%) escalation events. 16/159 (10%) escalations were not correctly predicted: 12/16 were escalations of medication (oral 5-aminosalicylic acid, n = 3), azathioprine (2), methotrexate (1), increase infliximab dose (2), adalimumab (3), tofacitinib (1). Other escalations were endoscopy requests (2), dermatology/rheumatology referrals (2). Importantly, 6/16 (38%) had taken steroids within 1 month of data collection. 143/403 (35%) of OPAs could have been deferred using a 5% ETI threshold. In contrast, increasing the ETI threshold to 25% would have allowed 274/403 (68%) OPAs to be deferred but would have resulted in missing an additional 53 escalations.

Conclusion

A model that predicts the likelihood of treatment escalation or intervention during an OPA, based on real-time data entered by patients, has the potential to improve outpatient clinic resource utilisation. The calculator may not be valid to triage patients recently on steroids.
P680 Biological treatment and potential risk of adverse postoperative outcome in patients with inflammatory bowel disease: An open-source expert panel review of the current literature and perspectives
Authors: El-Hussuna A
Published: January 2020

Background

There is widespread concern that treatment with biologics agents may be associated with sub-optimal postoperative outcome after surgery for inflammatory bowel diseases (IBD). We aimed to search and analyse the literature regarding the potential association of biologic treatment on adverse postoperative outcome in patients with IBD. We used the subject as a case in point for surgical research. The aim was not to conduct a new systematic review.

Methods

This is an updated narrative review written in a collaborative method by authors invited through Twitter via the following hashtags (#OpenSourceResearch and #SoMe4Surgery). The manuscript was presented as slides on Twitter to allow discussion of each section of the paper sequentially. A Google document was created which was shared across social media and comments and edits were verified by the primary author to ensure accuracy and consistency.

Results

Forty-one collaborators responded to the invitation, and a total of 106 studies were identified that investigated the potential association of pre-operative biological treatment on postoperative outcome in patients with IBD. Most of these studies were retrospective observational cohorts, 3 were prospective, 4 experimental and 3 population-based studies. These studies were previously analyzed in 10 systematic/narrative reviews and 14 meta-analyses. Type of biologic agents, dose, drug concentration, anti-drug antibodies, interval between last dose and types of surgery varied widely among the studies. Adjustment for confounders and bias control ranged from good to very poor. Only 10 studies reported postoperative outcome according to Clavien-Dindo classification.

Conclusion

Although a large number of studies investigated the potential effect of biological treatment on postoperative outcomes, many reported divergent results. There is a need for randomised controlled trials. Future studies should focus on avoiding the weakness of prior studies we identified. Seeking collaborators and sharing information via Twitter was integral to widening the contributors/authors and peer review for this paper, and was an effective method of collaboration.
P691 Corticosteroids usage in patients with inflammatory bowel disease: Results of a multi-national audit in Asia
Authors: Kim D H , Park D I , Kobayashi T , Ahuja V , Jang B I , Cao Q , Lee Y J , Ran Z
Published: January 2020

Background

The use of corticosteroids (CS) has been a well-established treatment for active Inflammatory bowel disease (IBD). While many investigators have reported the efficacy of CS in treating IBD, systemic CS are often associated with various side-effects. The aim of this study was to investigate the present status of CS usage in Asian patients with IBD.

Methods

Authors reviewed medical records of IBD patients who were regularly followed at multiple centres in South Korea, China, Japan, and India. Patient characteristics including diagnosis, phenotype, severity at diagnosis, and treatment history of CS usage in the prior 12 months were collected using web-based case report form. All cases of CS usage were reviewed of its suitability and were categorised as ‘non-IBD’, ‘appropriate’, and ‘avoidable’ groups.

Results

A total of 1,291 patients (434 Crohn’s disease [CD], 848 ulcerative colitis [UC], and 9 Indeterminate colitis) from 4 countries (18 physicians from 8 hospitals) were reviewed between May and September 2019. Among them, 339 patients (26.3%) received CS during the past year. There was no significant difference in the incidence of CS use between CD and UC patients. Multiple CS exposure over the recent 12 months were identified in 16 patients (4.7%). The mean duration of CS use was 96.5 days. Short-term and long-term side-effects of CS occurred in 21 (6.1%) and 4 (1.2%) patients, respectively. 285 patients (84.1%) were able to reduce the dosage of CS below the prednisolone equivalent of 10mg/day within 3 months from CS initiation without recurrence of the disease. However, 15 patients (4.4%) relapsed after stopping CS. A total of 340 CS used cases were confirmed in the 339 patients when cases with undeterminable suitability of its use were excluded and 36 events (10.6%) were classified as avoidable CS use. Patients who received ‘avoidable’ CS had longer disease duration than who received ‘appropriate’ CS (3227.5 days and 1450.5 days, respectively. p = 0.007). Both ‘avoidable’ and ‘appropriate’ group had started with similar CS dosage (37.2 and 38.8mg, respectively. p = 0.694). However, ‘avoidable’ group received CS longer than ‘appropriate’ group (125.7 and 37.7 days, respectively. p = 0.013). Multivariate analysis revealed that longer disease duration was significantly related with ‘avoidable’ CS exposure (OR=1.166; 95% CI=1.023–1.329; p = 0.022).

Conclusion

Treatment for IBD is advancing; however, a significant proportion of patients still receive CS. In particular, the longer the disease duration, ‘avoidable’ CS uses in patients tend to increase. Application of CS in patients with IBD should be delivered with much caution, as ‘avoidable’ CS use is associated with longer CS use.
P700 Effect of vitamin D in disease activity score and clinical relapse in patients with inflammatory bowel disease: A systematic review and meta-analysis
Authors: Guzman Y , Samson O , Segal J P , Limdi J K , Hayee B
Published: January 2020

Background

Vitamin D deficiency has been reported as highly prevalent among patients with inflammatory bowel disease (IBD) and current studies have demonstrated an association between low vitamin D status and an increased risk of clinically active disease, mucosal inflammation and clinical relapse. The aim of our study was to conduct a systematic review and meta-analysis exploring the effect of vitamin D supplementation in clinical and biochemical disease activity scores and relapse rate in patients with IBD.

Methods

We performed a search of major electronic databases (MEDLINE, EMBASE, Cochrane Library) and sources for grey literature (GreyNet international, Google Scholar, Web of Science) from inception to October 2019. Our search strategy was limited to the English and Spanish language. The results were supplemented by a manual search of the bibliographies of the shortlisted review and original study articles. Inclusion criteria: Adults (over 18 years old) with IBD (ulcerative colitis or Crohn’s disease); interventional (RCTs or non-RCTs) or observational studies; studies assessed the effect of vitamin D supplementation on disease activity scores and relapse rate. Exclusion criteria: Reviews, case reports, editorial, comment, letters; duplicates studies; insufficient data or unable to calculate outcome measures with available data. Mean difference was considered as the effect measure with 95% confidence interval (95% CI) and two sided P values. For relapse rate outcome, unadjusted OR were calculated using dichotomous data (events vs. total). Heterogeneity was assessed using χ2 test and I2 statistic. Review Manager software v.5.3 was used.

Results

A meta-analysis of five studies (n = 253) showed a lower relapse rate in vitamin D supplementation group compared with control group (OR: 0.33, 95% CI 0.18–0.61, p =  0.0004, I2: 0%) (Figure 1). Harvey Bradshaw Index improved by 1.52 points (95% CI: 0.14–2.90, p = 0.03, I2 51%) in vitamin D group compared with the score at baseline and C-reactive protein levels decreased compared with the levels at baseline (mean difference: 3.70 mg/l, 95% CI 0.10–7.29, p = 0.04, I2 0%) (Figures 2 and 3). Even though other studies reported different clinical remission tools such as SCCAI or CDAI, it was not possible to pool the results due to insufficient data to conduct a meta-analysis.

Conclusion

Our systematic review and meta-analysis provides evidence that vitamin D supplementation can improve clinical outcomes and reduce relapse rate in patients with IBD.
P708 The effect of psychotherapy on quality of life in inflammatory bowel disease patients: A systematic literature review
Authors: Paulides E , Boukema I , van der Woude C J , de Boer N K H
Published: January 2020

Background

Inflammatory bowel disease (IBD) is a chronic disease, both influencing patients physical and mental health and thereby interfering with quality of life (QoL). This systematic review aims to assess the effect of psychotherapy on IBD patients’ QoL.

Methods

A systematic search was conducted on 07 October 2019 using Embase, Medline (Ovid), PubMed, Cochrane, Web of Science, PsycInfo and Google Scholar, to collect all types of clinical trials with psychotherapeutic interventions that measured QoL in IBD patients aged 18 and over. Quality of evidence was assessed using GRADE criteria.

Results

Out of 2560 articles, 31 studies (32 articles) were included with a total number of 2397 patients. Of the 31 eligible studies, twelve showed a significant positive effect and four had mixed results regarding the impact of psychotherapeutic interventions on QoL. Eight studies were rated as of moderate quality, of which five showed a significant effect. All four studies focussing on patients with active disease showed a positive effect of psychotherapy. No specific preference for a type of psychotherapy, type of disease or psychological condition at baseline was found. No meta-analysis could be performed due to heterogeneity of design, implementation and statistical analyses of the studies.

Conclusion

Psychotherapeutic interventions can improve QoL in IBD patients, but there is mixed evidence. Patients with active disease seem to profit more from psychotherapy than those in remission. More high quality research is needed to provide tailored psychological therapy to adults with IBD.
P709 Is azathioprine safe as long-term treatment in paediatric patients with inflammatory bowel disease?
Authors: Martínez Ibeas M A , Bacelo Ruano I , Rodríguez Manchón S , Velasco Rodríguez-Belvís M , Viada Bris J F , Domínguez Ortega G , Muñoz Codoceo R A
Published: January 2020

Background

The toxicity of azathioprine (AZA) includes myelosuppression, infections, pancreatitis, photosensitivity, and hepatotoxicity. The aim of this study was to describe the adverse effects profile of azathioprine as long-term treatment in paediatric inflammatory bowel disease (IBD).

Methods

An observational, descriptive and retrospective study was performed in the paediatric IBD Unit of a tertiary care hospital from September 2008 to December 2018. It was included patients under 18 diagnosed with IBD who were treated with AZA during their follow-up. We recorded epidemiological data, thiopurine methyltransferase (TPMT) enzyme activity, AZA side effects, and the dosage the patients were receiving when these effects took place. Bone marrow suppression (BMS) was defined as leukopenia, thrombocytopenia and/or anaemia. Acute pancreatitis (AP) induced by azathioprine was considered when two of these criteria (Atlanta 2012) were met: lipase increase (> 3 times normal value), congruent signs and symptoms and/or echographic findings, without other possible aetiology and with complete recovery after AZA withdrawal.

Results

We included 52 patients, being 31 men (59.6%). They were diagnosed with Crohn′s disease (CD) (73%), ulcerative colitis (UC) (21%) and IBD-unclassified (6%). The median TPMT activity was 17 U/ml (14.2–19.2). Up to 63.5% developed adverse effects by AZA with a median time from the beginning of treatment of 11.4 months (2.6–26.4) and a median dosage of 2 mg/kg/day (1.7–2.3). The most frequent side effect was BMS (52%). These patients had a median TPMT activity of 16.9 U/ml (14.2–18.9), the median duration of treatment was 14 months (3.9–27.7), and the median dosage was 2 mg/kg/d (1.8–2.5). BMS was more frequent in patients with UC (p 0.04) and longer treatment (p 0.08). No differences were found according to age, sex or TPMT activity. Up to 11.5% developed AP, the median duration of treatment until its appearance was 1.5 months (0.7–43.3) and the median dosage was 2 mg/kg/d (1.5–2.5). No differences were found related to age, sex, diagnosis or dosage. Other side effects were: 3 flu-like symptoms, 3 opportunistic infections, 2 hypertransaminasemia, and 1 patient with elevated pancreatic enzymes and hyperbilirubinemia. AZA was discontinued in 14 patients (43.8%): in 6 due to AP, in 4 due to severe lymphopenia, in 2 because of Epstein-Barr virus infection, in 1 due to flu-like symptoms and in 1 with several adverse effects.

Conclusion

More than half of the patients treated with AZA presented side effects, mainly BMS, although most of them were mild and temporary, and the withdrawal of the drug was not necessary. It seems that TPMT activity is not useful to predict BMS, but this adverse effect could be related to a longer treatment.
P710 The influence of probiotics to the efficacy of 5-ASA for the patients of ulcerative colitis
Authors: YASUDA R , Uchiyama K , Takagi T , Kubota M , Sugino S , Azuma Y , Kitae H , Torii T , Takayama S , Inoue K , Katada K , Kamada K , Ishikawa T , Konishi H , Naito Y , Itoh Y
Published: January 2020

Background

5-ASA is a key drug to treat the patients with mild-to-moderate ulcerative colitis (UC). Probiotics is sometimes used to UC patients for the purpose to correct dysbiosis of intestine. In theory, the efficacy of 5-ASA, especially pH-dependent release formulation of mesalazine may be weakened by the co-treatment with probiotics because of its effect leading to acidic condition in large intestine. However, the detail analysis about UC patients treating with 5-ASA and probiotics has not been elucidated. In the present study, we demonstrated the clinical course of UC patients treated by 5-ASA with probiotics to investigate the effect of probiotics to 5-ASA treatment.

Methods

The subjects were 85 UC patients who were in clinical remission and taking 5-ASA at the hospital of Kyoto Prefectural University of Medicine from January to March 2014. The clinical characteristics (age, sex, clinical activity index, disease location, and type of 5-ASA) and the rate of relapse until October 2019 were compared between probiotics group and no probiotics group. Furthermore, the rates of relapse were analysed for each specific 5-ASA between probiotics user and no probiotics user. The clinical activity index (CAI) was determined using Lichtiger index. The relapse of UC is defined by the increase of CAI, additional medication for UC, and endoscopic deterioration of colonic mucosa.

Results

Patients were included 39 cases in probiotics group and 46 cases in no probiotics group. There was no significant difference between probiotics and no probiotics group on the average age (53.1 ± 16.8 vs. 51.3 ± 14.2 years old, p = 0.59), the rate of male gender (41.0% vs. 41.3%, p =0.97), the average CAI (2.1 ± 0.64 vs. 2.0 ± 0.73, p = 0.59), disease location (extensive/left/rectum: 20/7/12 vs. 21/10/15 cases, p = 0.31), and type of 5-ASA (salazosulfapyridine/time-dependent mesalazine/pH-dependent mesalazine: 5/18/16 vs. 6/18/22 cases, p = 0.46). Besides, there was no significant difference between probiotics group and no probiotics group (51.3% vs. 52.2%, p = 0.93) about the rate of relapse. Regarding each specific 5-ASA usage, there was no significant difference on salazosulfapyridine (40.0% vs. 33.3%, p = 1), time-dependent mesalazine (44.4% vs. 50.0%, p = 1), and pH-dependent mesalazine (62.5% vs. 59.1%, p = 0.90) between probiotics user and no probiotics user.

Conclusion

In the present study, the co-treatment with probiotics did not affect the relapse with UC patients regardless the type of 5-ASA, suggesting that the usage of probiotics might not disturb the efficacy of 5-ASA for UC patients.
P716 Clinical significance of residual non-rectal inflammation in ulcerative colitis patients with clinical remission
Authors: Shin J , Seong G , Song J H , Kong S M , Kim T J , Kim E R , Hong S N , Chang D K , Kim Y H
Published: January 2020

Background

The advancement of therapeutic agents has made it possible to achieve endoscopic remission in inflammatory bowel disease. Consequently, the treatment goal of ulcerative colitis (UC) also has been changed to achieve endoscopic remission (ER). However, there was insufficient clinical evidence of whether a step-up treatment should be performed to achieve ER in clinical remission (CR) without ER. And there is inadequate data on the need to consider the distribution and severity of residual inflammation in UC. This retrospective study aimed to evaluate the prognostic significance (such as step-up therapy, hospitalisation, and colectomy) of the distribution and severity of residual inflammation in UC patients with CR.

Methods

A total of 134 UC patients who underwent endoscopic evaluation in CR and underwent colonoscopy more than 3 times between January 2000 and December 2018 were retrospectively reviewed. Patients were allocated by endoscopic healing state and distribution of inflammation to an ER (n = 33, 24.6%), residual non-rectal inflammation with patchy distribution (NRI) (n = 17, 12.7%) or residual rectal involvement with continuous or patchy distribution (RI) (n = 84, 62.7%). We reviewed the patient’s characteristics, endoscopic findings and ascertain poor outcome-free survival (PFS) until June 2019.

Results

In UC patient with CR, the PFS was significantly better in ER and NRI (p = 0.003). ER and NRI had similar PFS (p = 0.683). The baseline clinical characteristics of NRI and RI were not significantly different except for the pattern of residual inflammation (p < 0.001). Multivariate analysis showed that NRI was a good prognostic factor of PFS for UC with CR Like ER (hazard ratio 0.53 (0.05–6.30), p = 0.615).

Conclusion

There was no statistically significant difference in the PFS between ER and NRI in the CR state of UC patients. Therefore, we propose selective escalation of treatment modality in CR patients, even if they do not reach ER.
P719 Effectiveness and safety of ustekinumab induction therapy in ulcerative colitis: A GETAID real-world cohort study
Authors: Amiot A , Vered A , Filippi J , Cadiot G , Laharie D , Melanie S , Altwegg R , Bouhnik Y , Peyrin-biroulet L , Gilletta C , Roblin X , Pineton de chambrun G , Vuitton L , Bourrier A , Nancey S , Gornet J M , Nahon S , Bouguen G , Viennot S , Benjamin P , Fumery M
Published: January 2020

Background

Phase III trials have demonstrated the efficacy and safety of ustekinumab in moderate-to-severe ulcerative colitis (UC), but no real-life data is currently available.

Methods

Between January and September 2019, all consecutive patients with UC treated with ustekinumab in 20 French GETAID centres were included. The primary outcome was steroid-free clinical remission (partial Mayo Clinic score ≤ 2) at weeks 12–16 without rectal bleeding subscore > 1.

Results

One hundred and three patients were included with a median age and disease duration of 39.3 [interquartile range (IQR), 29.1–52.3] and 7.6 [3.6–12.9] years, respectively. Most of the patients had left sided colitis (41.8%) or pancolitis (52.4%). History of immunomodulator, anti-TNF and vedolizumab therapies was noted in 84.5%, 99.0% and 85.4% of the cases, respectively. Steroid-free clinical remission and clinical remission rates were 35.0% and 39.8% at weeks 12–16, respectively. Normalisation of rectal bleeding and stool frequency (subscore 0 for both outcomes) was noted in 19.4% of patients whereas normalisation of rectal bleeding (subscore 0) with a stool frequency subscore of 0 or 1 was noted in 39.8%. Two patients discontinued ustekinumab before the weeks 12–16 visit and were referred to surgery. Predictors of therapeutic failure at weeks 12–16 were a partial Mayo Clinic score > 6 at week 0 (HR = 10.0, 95%CI [1.11––100.0], p = 0.04) and an history of previous use of anti-TNF and vedolizumab (HR = 33.3, 95%CI [2.4–100.0], p = 0.01). Improvement in endoscopic activity of UC at weeks 12–16 was observed according to Ulcerative Colitis Endoscopic Index of Severity (5.0 ± 1.2 vs. 3.8 ± 1.9, p < 0.001). Adverse events occurred in 7.8% and serious adverse events in 3.9%.

Conclusion

In this first real-life cohort study of refractory UC patients treated with ustekinumab, clinical remission without corticosteroids was observed in one-third of cases at weeks 12–16. Clinical severity and previous use of anti-TNF and vedolizumab were associated with therapeutic failure.
P724 Delaying an infliximab infusion by more than 3 days is associated with a significant reduction in trough levels
Authors: Ungar B , Ben-Shatach Z , Ziv-Baran T , Fudim E , Yavzori M , Picard O , Selinger L , Weiss B , Kopylov U , Eliakim R , Ben-Horin S
Published: January 2020

Background

An association between higher infliximab-trough-levels (TL) and better outcomes has been demonstrated among IBD patients. Although standard scheduled infliximab therapy regimen consists of infusions at pre-defined time-points (weeks 0, 2, 6 and every 8 weeks), short-period deviations from therapeutic schedule are common in ‘real life’, especially during maintenance period (due to weekends, holidays, concurrent illnesses, etc.). We aimed to determine whether short-period deviations from infusion-schedule affect infliximab-TL and therapy outcome.

Methods

This was a retrospective study, analysing sera from all IBD patients receiving infliximab maintenance-therapy every 8 weeks in a tertiary medical centre. Associations between time since last infusion and TL were analysed. Clinical scores were recorded prospectively on infusion days and baseline demographic parameters were derived from patients’ charts. Statistical analysis was performed using generalised estimating equations.

Results

In total, 2088 sera of 302 maintenance-period infliximab-therapy-patients were included (median TL 4.1 μg/ml, IQR 2.3–6.5 μg/ml). A delay beyond 3 days in infusion (n > 59 days since last infusion) was demonstrated as significantly affecting TL (mean difference in TL 1 μg/ml, 95% CI 0.03–1.9 μg/ml, p < 0.04). A sub-analysis was performed for 60 maintenance-period infliximab-therapy-patients with >10 consecutive TL measurements (1226 measurements in total), with adjustment for background parameters (gender, infliximab dose, disease type, concomitant immunomodulator, age and weight). A delay of >4 days from scheduled infusion resulted in a statistically significant decline in infliximab trough levels (mean difference in TL 1.45 μg/ml, 95% CI 0.61–2.2 μg/ml, p < 0.001). Finally, deviation from infusion schedule was analysed in association with clinical remission status. Patients that were in clinical remission were more likely to arrive late, rather than early, for scheduled therapy, compared with patients with active disease (OR 2.92 CI 1.75–4.85, p < 0.0001).

Conclusion

Real life delays of <4 days from infusion protocol can probably be allowed. Delays beyond that would significantly decrease TL and might negatively affect therapy outcome. As patients arriving late for an infusion had higher rates of clinical remission than those arriving early, we assume clinical factors mainly drive patients to receive an earlier-then-scheduled infusion.
P740 Age determines the risk of familial IBD: A nationwide case–control study
Authors: Halfvarson J , Ludvigsson J , Sachs M , Askling J , Olén O
Published: January 2020

Background

A family history of inflammatory bowel disease (IBD) is a proxy for an individual’s genetic and, in part, environmental risk of developing IBD, and is one of the strongest known risk factors for developing IBD. Although a familial aggregation is a well-established concept, data on its strength and nature are sparse. Therefore, to provide precise estimates of the familial aggregation, we performed a nation-wide, case-control study and examined the relative risk for patients with IBD (vs. population controls) to have a first-degree relative (FDR) with IBD, by age of onset, type of family history, and IBD subtype.

Methods

Individuals diagnosed with IBD between 1 January 2003 and 31 December 2017 with at least one first degree relative (FDR) were identified from Swedish national registers and compared with non-IBD controls, with at least one FDR, from the general population. We used logistic regression to calculate odds ratios (ORs) as estimates of relative risk for IBD in FDRs taking age at IBD onset, sex, county, and year of IBD diagnosis into account.

Results

We identified 50,667 incident cases with IBD (CD, n = 14,927; UC, n = 27,221 and IBD-U, n = 8519) and 506,720 controls, matched for age, sex, birth year and county of residence. The overall familial relative risk estimate of IBD for siblings (OR 3.6 [95% CI 3.4–3.8]) was similar to that between generations (OR 3.5 [95% CI 3.3–3.7] for mothers and OR 3.5 [95% CI 3.3–3.7] for fathers). Half-siblings conferred a lower yet elevated relative risk (OR 2.0 [95% 1.8–2.2]). The familial relative risk estimates of IBD increased with number of affected FDRs (Figure 1). Pronounced differences were seen between subtypes of IBD in the index case and also across age of onset in the index case and in the FDR (Figure 2). Lowest odds ratios were seen for having an FDR with elderly onset IBD among cases who were diagnosed with elderly onset Crohn’s disease (OR 1.9 [95% CI 1.4–2.5]) or ulcerative colitis (OR 1.9 [95% CI 1.5–2.3]). Highest odds ratios were seen for having an FDR with paediatric onset IBD among cases who were diagnosed with paediatric Crohn’s disease (OR 10.6 [95% CI 8.2–13.5]) or paediatric ulcerative colitis (OR 8.4 [95% CI 6.4–10.9]).

Conclusion

The relative risk of familial IBD varies by IBD subtype as well as by age of onset in the index patient with IBD and the FDR, pointing to differences in genetic predisposition and environmental risks between different phenotypes of IBD.
P741 Incidence and clinical phenotype of inflammatory bowel disease in the north–west of Spain (Vigo) between 1991 and 2011
Authors: De Castro Parga M L , De Castro Luisa Hernández V , Pineda J R , Martinez Cadilla J , Figueira M , Sanromán L , Pereira S , Rodriguez-Prada J I
Published: January 2020

Background

The incidence of inflammatory bowel disease (IBD) seems to have stabilised in the last two decades in some western countries. Our aim was to analyse changes in the epidemiology of IBD between 1991 and 2011 in the area of Vigo (north–west of Spain).

Methods

Retrospective and descriptive study of two inception cohorts of IBD patients aged 15 years or more, that were enrolled in the area of Vigo in two European epidemiological studies: EC-IBD performed from 1991 to 1993 and EpiCom performed in 2010 and 2011. The population of Vigo at those moments was of 408.387 and 493.516 inhabitants, respectively.

Results

In 1991–1993, 102 new IBD cases were diagnosed: 65 ulcerative colitis (UC), 35 Crohn’s disease (CD) and 1 IBD unclassified (IBDU) that showed an incidence of 12.5 cases/100 000 inhabitants per year (8/100 000 inhabitants/year for UC, 4.3/100 000 inhabitants/year for CD and 0.1/100 000 inhabitants/year in IBDU). Regarding 2010–2011, there were 192 cases: 88 UC, 83 CD, 21 IBDU, which an incidence of 19.5 cases/100 000 inhabitants per year (8.9/100 000 inhabitants/year for UC, 8.4/100 000 inhabitants/ year for CD and 2/100 000 inhabitants/year for IBDU) (Figure 1). IBD patients in the second cohort were older: 43.5 (16.4) and 35.8 (16.2) years (p = 0.0005) than the first ones, and IBD diseases also differed in both cohorts (p = 0.001) with more CD (p = 0.03) and IBDU (p = 0.013) in 2010–2011. In 2010–2011 cohort UC patients were older: 39.2 (15.1) vs. 46.1 (16.4) years (p = 0.008) with no differences in gender or phenotype. CD patients were older as well: 29.1 (15.7) vs. 40.4 (15.8) year (p = 0.001), with more patients over their 40s (p = 0.005), and an increase in ileal vs. colonic location (53% vs. 20%, p = 0.006) (Table 1).

Conclusion

Between 1991 and 2011, an increase in the incidence of IBD in Vigo was demonstrated, mainly in CD and IBDU. The age at IBD diagnosis increased significatively, both in UC and CD.