bluuebunny/crossref_metadata_2025 huggingface dataset:
P307 Modelling of the relationship between ustekinumab exposure, faecal calprotectin and endoscopic outcomes in patients with Crohn’s disease
Authors: Wang Z , Verstockt B , Vermeire S , Sabino J , Ferrante M , Declerck P , Dreesen E
Published: May 2021

Background

In the UNITI endoscopy sub-study, only 17.4% of patients with Crohn’s disease (CD) on ustekinumab achieved endoscopic response and 10.9% achieved endoscopic remission at week (w)44. We aimed to investigate if improved endoscopic outcomes can be achieved through dose optimisation based on a population pharmacokinetic-pharmacodynamic (popPK-PD) modelling and simulation analysis.

Methods

Real-world data were obtained from 83 patients with moderate-to-severe CD (94% multi-refractory) enrolled in a prospective cohort study receiving ustekinumab 6 mg/kg induction and every eight-week (q8w) 90 mg maintenance therapy. Ustekinumab serum concentrations were measured at mid-dose (w4) and trough (w8, w16, w24). Faecal calprotectin (fCal) was measured at baseline and at w4, w8, w16, w24. Endoscopic response (≥50% decrease in simple endoscopic score for CD [SES-CD]) and endoscopic remission (SES-CD ≤2) were assessed at w24. Modelling and simulation were performed using NONMEM 7.4.

Results

Three sequential models were developed: a two-compartment popPK model linking ustekinumab dose to ustekinumab exposure, an indirect response popPK-PD model describing the effect of ustekinumab exposure on fCal, and a logistic regression popPD model linking fCal at w8 to endoscopic outcomes at w24 (Figure 1). Ustekinumab clearance increased with decreasing serum albumin and increasing bodyweight. The terminal half-life of ustekinumab in a median patient (bodyweight 65 kg, serum albumin 42.7 g/L) was 20.4 days. fCal decreased with increasing ustekinumab exposure. The probability of endoscopic response at w24 increased from 10.0% to 17.9% with fCal at w8 decreasing from 1,800 μg/g to 694 μg/g (Figure 2a) The probability of endoscopic remission at w24 increased from 2.1% to 10.0% with fCal at w8 decreasing from 1,800 μg/g to 214 μg/g (Figure 2b).The results from the simulation-based comparison of q8w and q4w maintenance dosing are shown in Table 1. Dose doubling (180 mg q8w), as opposed to interval halving (90 mg q4w), was predicted to result in a ustekinumab trough concentration of 2.4 μg/mL instead of 4.8 μg/mL.

Conclusion

The developed model can guide clinical trial design and support model-informed dose optimisation to improve endoscopic outcome rates. Although our analyses showed that q4w dosing resulted in higher ustekinumab and lower fCal concentrations, the proportion of patients achieving endoscopic remission was limited.
P308 Effectiveness and Safety of tofacitinib for the Treatment of Ulcerative Colitis: A Single-Arm Meta-analysis of Observational Studies
Authors: Macaluso F S , Maida M , Ventimiglia M , Orlando A
Published: May 2021

Background

Several observational studies on Tofacitinib (TOFA) for the treatment of ulcerative colitis (UC) have been published over the last 2 years. The aim of this single-arm meta-analysis was to estimate the effectiveness and safety of TOFA arising from real-world observational studies.

Methods

PubMed Central/Medline and Embase, as well as reference lists of articles, were systematically searched for real-world observational studies of TOFA for the treatment of UC through November 2020.

Results

Seven studies comprising 759 patients met the inclusion criteria. Almost all patients (range: 76.5-100%) had been previously exposed to anti-TNFs, and a variable proportion (range: 38.8-100%) had been previously treated with Vedolizumab The pooled estimate rates were 49% for clinical response, 40% for clinical remission, and 34% for corticosteroid-free clinical remission at induction, while the rates of endoscopic response and endoscopic remission were 37% and 19%, respectively. At maintenance, the pooled estimate rates of clinical response, clinical remission, and corticosteroid-free clinical remission were 36%, 35%, and 24%, respectively. The pooled estimate of incidence rate of total adverse events was 53.0 per 100 person-years (PY), while the pooled estimate of incidence rate of withdrawal of TOFA due to adverse events was 9.3 per 100 PY, with a pooled rate of infections of 17.6 per 100 PY.

Conclusion

Cumulative analysis of data from real-world studies confirmed the good efficacy of TOFA in UC shown by randomized controlled trials for both induction and maintenance, while the safety profile was consistent with previous reports.
P317 Societal cost-of-illness of Inflammatory Bowel Disease has rapidly increased over the years and differs between continents: A systematic review
Authors: Van Linschoten R , Visser E , Niehot C , van der Woude J , Hazelzet J , van Noord D , West R
Published: May 2021

Background

With increasing incidence of Inflammatory Bowel Disease (IBD) in developing countries and increasing prescription rates for biologics globally, knowledge on the cost burden of IBD and cost drivers is essential for health policy makers worldwide. We conducted a systematic review to determine cost-of-illness of IBD and assess time trends and geographical differences.

Methods

A systematic review of population-based studies that estimated cost-of-illness of IBD and were published in Embase, Medline, Web of Science and Google Scholar. Studies on interventions and those reporting costs for a subset of patients defined by phenotype or treatment were excluded, as these do not give a representative estimate of the cost-of-illness of IBD. Only studies published in English were included. Methodology of all included studies was assessed and costs were adjusted to 2018 US dollars.

Results

In total, 4,837 unique studies were screened on title and abstract and 4,730 excluded. After full-text screening, 64 of the remaining 107 studies were included in the systematic review. The study methodologies differed considerably, with large differences in perspective, valuation method and source population. Mean annual healthcare costs for prevalent Crohn′s disease (CD) cases in the last 10 years were in Asia $4,463; Europe $12,396 and North America $17,508. Costs for prevalent ulcerative colitis (UC) patients in the same period were $1,654, $7,206 and $13,569 respectively. For CD, the cost drivers moved from inpatient (61% of total costs) in 1995 to medication costs (77%) in 2016. Similar trends were identified for UC (1998: 50% and 36% versus 2016: 9%, and 82% for inpatient and medication costs, respectively). This cost trend is primarily attributable to an increase in medication costs in all four geographical areas, while in- and outpatient costs were relatively stable during the same time period. The annual costs of absenteeism and presenteeism per prevalent case of CD were $5,638 in Asia and $6,485 in Europe. For UC these costs were $4,828 and $6,414 respectively. Annual costs of absenteeism and presenteeism in North America were $20,074 per patient for a combined cohort of UC and CD patients.

Conclusion

Per patient costs for IBD are increasing worldwide, with highest costs in North America and lowest in Asia. This is primarily due to an increase in medication costs. Productivity costs are substantial and might even exceed healthcare costs. Biologic therapy was expected to decrease inpatient costs by reducing hospitalisations and surgery, but this does not appear to be the case. Continuing growth of these costs can lead to an intolerable burden on healthcare systems worldwide.
P320 Combined mesenchymal stromal cells and anti-cytokine therapy of perianal Crohn’s disease
Authors: Knyazev O , Kagramanova A V , Lishchinskaya A , Shkurko T , Li I , Parfenov A
Published: May 2021

Background

Perianal fistulas are common types of fistulas in Crohn’s disease (CD). Mesenchymal stromal cells (MSC), which have immunomodulatory properties and high regenerative potential, are currently also used for the treatment of fistula CD.

The purpose of this study was to compare the effectiveness of combined therapy (local and systemic) mesenchymal stromal cells (MSC) of bone marrow, in the effectiveness of combination therapy MSC (local administration) and infliximab (IFX), as therapy the IFX with immunomodulators on the healing of simple perianal fistulas in Crohn’s disease (CD).

Methods

Seventy-five patients with CD with perianal lesions were divided into three groups depending on the method of therapy. The first group of СD patients aged 19 to 59 years (Me-29) (n=25) received a culture of MSC systematically according to the scheme and locally. The second group of patients with CD (n=25) aged 20 to 60 years (Me-28) received anti-cytokine therapy with IFX and immunomodulators. The third group of patients with CD (n=25) aged 20 to 62 years (Me-30) received MSC systemically and locally, as well as anti-cytokine therapy with IFX. The dynamics evaluated the complete closure of the external opening of the fistula. Ano-and rectosigmoscopy was performed 2 and 12 months after the start of therapy. The comparative analysis was performed using four-field tables using nonparametric statistical criteria.

Results

After 2 months in the first group of patients, healing of simple fistulas was observed in 15/25 (60.0%), in the third group-22/25 patients (88.0%) (RR–1.467; 95% CI - 1.032-2.084; x2= 3.742; p=0.02948).

After 2 months in the second group, healing of simple fistulas was observed in 16/25 (64.0%) (RR-1.37; 95% CI 0.991-1.908; x2=4.091; p=0.056).

After 12 months in the first group of patients, healing of simple fistulas was observed in 17/25 (68.0%), in the third group-24/25 (96.0%) patients (RR 1.412; 95% CI 1.066–1.869; x2=7.399; p=0.0124).

After 12 months in the second group, healing of simple fistulas occurred in 18/25 (72.0%) (RR -0.750; 95% CI 0.580– 0.970; x2=5.922; p=0.0488).

Conclusion

Combined cells and anti-cytokine therapy of CD with perianal lesions contributes to more frequent and prolonged closure of simple fistulas, compared with MSC monotherapy and IFX monotherapy.
P348 Perception of cancer risk in inflammatory bowel disease-associated dysplasia and management practice is influenced by colonoscopy experience and workplace affiliation: results of an international clinician survey
Authors: Kabir M , Thomas-Gibson S , Hart A , Wilson A
Published: May 2021

Background

A successful inflammatory bowel disease (IBD) surveillance cancer preventative programme requires effective action to be taken when dysplasia is detected. This is the first international cross-sectional study to evaluate current clinician understanding of IBD dysplasia risk, their management practice and adherence to the most recent international guidelines introduced since 2015.

Methods

A 15-item online survey was disseminated to IBD gastroenterologist and colorectal surgeon members of the British Society of Gastroenterology in June 2019 and the European Crohn’s and Colitis Organisation in February 2020.

Results

294 clinicians (93.5% gastroenterologists) from 60 countries responded. A significant proportion indicated not having access to high definition chromoendoscopy IBD surveillance (23%) in their endoscopy units. University hospitals were more likely than non-academic workplaces to provide second expert histopathologist review (67% vs. 46%; p=0.002) and formal multidisciplinary team meeting discussion (73% vs. 52%; p=0.001) of dysplasia cases. Most respondents would advocate endoscopic resection of all visible dysplasia and would refer to a regional specialist therapeutic endoscopist if needed (70%). However, perceptions of 5-year cancer risk associated with endoscopically unresectable low-grade dysplasia (LGD) varied between 0 – 100% (median 20% for visible LGD and median 25% for invisible LGD). Although most (98.4%) would advise a colectomy for endoscopically unresectable visible high-grade dysplasia (HGD), only 34.4% would also advise a colectomy for unresectable visible LGD. Working at a non-academic hospital was predictive of a lower perceived cancer risk with HGD [OR 0.4 (95% CI 0.23-0.95)] and unresectable LGD. Working in a private clinic predicted surveillance preference over colectomy to manage invisible LGD [OR 9.4 (95% CI 1.19-74.1)] and multifocal LGD. Greater surveillance colonoscopy experience predicted a lower preference for continued surveillance over colectomy for invisible LGD [OR 0.41 (95% CI 0.20-0.84)].

Conclusion

This study of mainly European gastroenterologists with a sub-specialist interest in IBD has revealed wide variations in colorectal cancer risk perceptions and dysplasia management practices. Clinicians with less IBD surveillance colonoscopy experience and from non-academic centres appeared to have lower cancer risk perceptions and were less likely to advocate colectomy over continued surveillance for high-risk LGD. This study suggests that further education is required to align current management practice with clinical guidelines.
P377 Inadequate response with advanced therapies in real-world patients with Ulcerative Colitis – Results of a German claims database study
Authors: Bokemeyer B , Picker N , Wilke T , Rosin L , Patel H
Published: May 2021

Background

Therapeutic management of Ulcerative Colitis (UC) is challenging, and clinicians are often obliged to attempt a variety of therapies in sequence until an adequate clinical response is achieved. However, real-world data regarding response rates in UC treatment are rare, particularly for later lines of therapy. Thus, this study aimed to investigate the incidence of inadequate response to advanced therapies in patients with UC.

Methods

This retrospective study was based on claims data from a regional German sickness fund covering the period from 01/2014-06/2019. Patients were included if they had at least two outpatient diagnoses in two different quarters or one inpatient diagnosis of UC (ICD-10: K51) and started a newly introduced advanced therapy (adalimumab, golimumab, infliximab, tofacitinib, vedolizumab) in 01/2015-06/2019. Patients were followed from treatment initiation (index date) until the end of the study period or loss to follow-up (median = 23.4 months).

Proxies of inadequate response included: discontinuation (a supply gap of >60 days), switch, escalation (as dose increase exceeding 1.5 times the recommended maintenance dose), augmentation with 5-ASA, corticosteroid (CS) dependency (two CS prescriptions were observed starting more than 14 weeks after the index date), UC-related hospitalization, or UC-related surgery. CS dependency and treatment escalation were only assessed in the maintenance phase. Inadequate response in the analyzed sample was evaluated by means of Kaplan-Meier survival analysis.

Results

Among 574 UC patients (median age: 39 years; female: 53.5%), in whom an advanced therapy was initiated, 458 (79.8%) received an anti-TNF therapy, 113 (19.7%) vedolizumab and 3 (0.5%) tofacitinib. According to the available baseline period, 72 (12.4%) patients were identified as biologic-experienced. Most patients received CS (86.4%) and/or 5-aminosalicylic acids (81.7%) in the 12-month pre-index period. The median time to inadequate response to the initiated advanced therapy was 4.8 months (IQR: 2.6-11.9; Figure 1) with an inadequate response over 12 months in 75% (Figure 2). There was no significant difference in median time to inadequate response between biologic-naïve and biologic-experienced patients (4.9 vs. 4.7 months; p-value = 0.285). During the observable follow-up period, 172 (61%) patients switched from their index agent to another advanced therapy.

Conclusion

From the real-world settings in Germany, we found an inadequate response in UC-patients starting an advanced therapy in 75% of patients over 12 months. There is a need for more effective therapies among these patients.
P434 Factors associated with medical and psycosocioeconomic changes in IBD during the COVID-19 pandemic and post-pandemic period
Authors: Hu S , Wang X , Shen B , Yu Q , Zheng J J , Chen Y
Published: May 2021

Background

The pandemic of COVID-19 had posed challenges in every aspect of the people’s life. COVID-19 had affected all age groups in both previously healthy individuals and those with chronic disease including IBD. This study aimed to investigate the occurrence and factors associated with psychosocioeconomical and medical changes in patients with IBD during the COVID-19 pandemic and post-pandemicperiod in China.

Methods

The survey questionnaires were sent to the patients with IBD in China including epicentres and outside. Bivariate analyses and logistic regression models were used to analysis associations between IBD and various demographic, disease factors, and patient-reported outcomes including working conditions, income, anxiety, stress, and sadness.

Results

Of the 2277 respondents, 144 (6.3%) respondents were from Hubei province which was the epicenter of COVID-19 in China. Multivariable regression demonstrated that patients had part-time work (odds ratio [OR]: 4.28; 95% confidence interval [CI]: 2.48-7.36; P<0.001) or those had middle education level (high school graduate and bachelor’s degree) (OR:7.28; 95%CI: 3.58-14.81; P<0.001) were more likely to have reduced income compared with those had full-time work or less than high school education level. In addition, female (OR: 1.41; 95%CI: 1.16-1.71; P= 0.01) patients were at higher risk of having an anxiety, stress and sadness disorder. While un-married patients (OR: 0.76; 95% CI: 0.63-0.91; P=0.003) patients were less likely to have mood changes. Moreover, IBD patients with active disease (OR: 4.79; 95% CI: 3.87-5.91; P<0.001) were at higher risk of IBD medication changes.

Conclusion

The results from this large survey demonstrated that the COVID-19 pandemic affected the patients with IBD financially, psychosocially, and medically. Our findings highlighted the importance of screening for psychosocioeconomic and medical changes in patients with IBD, with particular attention to those of female sex, have part-time work, and active disease. Our IBD community needs to develop effective and feasible strategies to deal with current and future challenges such as a viral pandemic.
P446 Plasma rich in growing factors as treatment for perianal fistulas in Crohn’s disease: unicentre experience
Authors: Soto Sánchez A , Hernandez Camba A , Hernández M , Hernández G , Pérez Sánchez E , Barrera Gómez M
Published: May 2021

Background

Perianal Crohn’s disease (PCD) adds a significant morbidity and reduced quality of life. Complex fistulas occur in up to 20% of patients. The available treatment of PCD includes immunosuppressive drugs, antibiotics, different surgeries but are associated with high recurrence rates. A new alternative using plasma rich in growth factors (PRGF) for the treatment of complex fistulas has emerged from to achieve better healing with the minimum possible complications without affecting anal continence. This study aims to assess the feasibility, safety and efficacy of local injection of PRGF in patients with PCD.

Methods

Retrospective observational and descriptive study analyzing 6 Crohn′s Disease (CD) patients undergoing complex anal fistula sealing with PRGF from March 2019 to December 2020. All patients underwent endoanal ultrasound and 60% a pelvic magnetic resonance also. The technique consisted of locating the tract without the use of hydrogen peroxide, active curettage of the tract and closure the internal fistulous orifice (IFO) with single stitches Vicryl® 3/0. Subsequently, 50% of the PRGF-rich fraction was injected in the submucosa of the closed internal fistula orifice. The other 50% is injected in the fistulous tract. With PRGF-poor fraction a three-dimensional fibrin matrix is created and filled the previously curetted fistulous tract. We describe the results in terms of demographic variables, outcomes, surgical procedure and complications. Endpoint was fistula closure by physical examination and endoanal ultrasound.

Results

Sixty seven percent of the patients were female, mean age was 43 (26y SD). The clinical characteristics of the patients are described in table 1. All of the patients had previous abscess drainage surgery. The most frequent fistula was mid-transsphincteric type. 66.7% had seton at the time of surgery and only one patient had no medical treatment at that time. The median follow-up was 30 months. The recurrence rate was 66.7% with no differences with in age, sex, comorbidity, type of fistula, fistula location, medical treatment and whether they had a seton implanted at the time of surgery. No patient presented complications. The median follow-up was 16 months.

Conclusion

PRGF sealing appears to be feasible, safe and a promising option in the treatment of PCD. Further studies should be carried out to determine the real use of PRGF in PCD.
P450 Vaccination strategies in Inflammatory Bowel Disease patients: perspective of physicians and patients
Authors: Ferreiro Iglesias R , Hernández Camba A , Saldaña R , Rodríguez-Lago I , Zabana Y , Barreiro-de Acosta M
Published: May 2021

Background

Despite the existence of specific recommendations, patients with Inflammatory Bowel Disease (IBD) have shown low immunization rates. The aim of this study was to evaluate the management of vaccines in clinical practice in IBD from the perspective of physicians and patients.

Methods

An online anonymous survey was sent to 8000 patients from a national patient association (ACCU-Spain) and 1000 members of the Spanish IBD Working Group (GETECCU). Three invitations were sent between October-December 2020. Forty questions were jointly designed by ACCU and GETECCU in two different surveys for physicians and patients. Descriptive analyses were performed, comparing physician’s and patient’s responses by standard statistical analyses

Results

144 physicians and 1302 patients responded to the surveys (overall mean age of 43 years (SD 9.5). 65% of physicians managed more than 200 patients and 80% had >5 years of experience. Most physicians (99%) were concerned about vaccines in IBD patients in their clinical practice, and 63% of them considered vaccines very important. Only 3.5% of physicians recommended live vaccines for their IBD patients with immunosuppressive treatments. One third of physicians did not recommend HPV vaccine. In spite of 69% of physicians recommending influenza vaccine during pregnancy, only 7.2% of pregnant patients indicated that they had received advice on influenza vaccination on their pregnancy (p<0.001). Only 16.6% of physicians recommended live vaccines during the first year of life in children born to mothers exposed to biologics, and 4.4% did not recommend inactive vaccines. Moreover, patients treated with biologics considered that physicians were well trained in vaccines, compared to those treated with other drugs. Table 1 summarizes the perspective of physicians and patients.

Conclusion

Deficiencies in knowledge regarding vaccination of IBD patients can be frequent. The perspective of physicians and patients is different, with physicians perceiving more recommendations related to vaccines than patients were recommended.
P512 Safety of reduced clinical monitoring in patients with stable Inflammatory Bowel Disease on maintenance thiopurine therapy
Authors: Jansen F M , Smits L S , Thomas P W A , den Broeder N , de Jong D J , van Dop W A , Hoentjen F
Published: May 2021

Background

Thiopurine-treated inflammatory bowel disease (IBD) patients are monitored every 3 to 4 months with outpatient visits and laboratory assessments to evaluate disease activity and safety of therapy. However, the risk of thiopurine-related adverse events decreases after the initiation phase. The aim of this study was to assess the safety of reduced clinical monitoring in steroid-free quiescent IBD patients on stable maintenance thiopurine monotherapy.

Methods

This single-centre prospective cohort study evaluated a reduced monitoring strategy that involved 6-monthly laboratory assessment combined with alternating outpatient and phone appointments, during 104 weeks. We enrolled IBD patients who were in steroid-free remission > 6 months on thiopurine monotherapy including azathioprine, 6-mercaptopurine or tioguanine. The primary outcome was thiopurine-related adverse events (AE) requiring change or discontinuation of thiopurine therapy after 104 weeks of follow-up. Secondary outcomes were assessed at week 52 and included other thiopurine-related AEs and laboratory abnormalities.

Results

We included 85 patients (42 years median age, 61.2% Crohn’s disease, 62% female) with a median disease duration of 12.5 years. At baseline, 47 patients were treated with azathioprine (55.3%), 25 with 6-mercaptopurine (29.4%) and 13 with tioguanine (15.3%) for a median duration of 6.7 years. During 104 weeks of follow-up, thiopurine therapy was ceased in two patients because of multiple infections (n=1) and gastrointestinal complaints (n=1). Other reasons for thiopurine cessation (n=37) were stable remission (n=26), patient preferences (n=9) and high 6-TGN levels (n=2). In total, 20 patients underwent thiopurine dose adjustments due to high metabolite levels (n=9), remission (n=3), disease flare (n=3), patient preferences (n=3), and low metabolite levels (n=2). At 52 weeks, 27 laboratory abnormalities were observed, yet none required therapy adjustments. In 13 patients (15.3%) myelotoxicity was detected, including mild leukopenia (n=11), mild and moderate thrombopenia (n=2). In 16.5%, hepatoxicity was observed (n=14) including mild (n=9) and moderate (n=1) elevated aspartate aminotransferase and mild elevated alkaline phosphatase (n=4).

Conclusion

A reduced monitoring strategy appeared relatively safe in a strictly selected cohort of stable thiopurine-treated IBD patients. Overall, two patients had to cease thiopurine therapy due to thiopurine-related AEs independent of monitoring frequency. No laboratory abnormalities required therapy adjustments and 57.1% of patients continued therapy throughout 104 weeks of follow-up. This strategy may contribute to safe reduction of time and health care costs for both IBD patients and physicians in daily IBD practice.
P514 Influence of the frequency of glucocorticosteroid therapy courses on the hormonal resistance in patients with ulcerative colitis
Authors: Knyazev O , Tishaeva I , Kagramanova A , Shkurko T , Veselov A
Published: May 2021

Background

One of the most effective anti-inflammatory agents in ulcerative colitis (UC) are glucocorticosteroids (GCS), which block the release of arachidonic acid, prevent the formation of inflammatory mediators, have an immunomodulatory effect, affect tissue fibrinolysis, which leads to a decrease in inflammation and bleeding of the mucous membrane. However, in 9–16% of patients UC, hormone resistance develops.

Objective

to establish the dependence of hormonal resistance on the frequency of GCS courses for 12 months without taking into account the starting dosage of GCS.

Methods

96 patients with moderate to severe UC (Truelove-Witts) who received several courses of GCS. Males 51 (53.1%), females 45 (46.9%). The median age was 34±4.2 years. The duration of the anamnesis was from 3 to 7 years (Me 4 years). Patients were divided into three groups depending on the frequency of GCS courses for 12 months without taking into account the starting dosage of GCS. Group 1-st (n=30) received ≤1 course of GCS for 12 months for UC exacerbation, group 2-nd (n=34)-1–2 courses of GCS, group 3-rd (n=32)-3 ≥ courses of GCS. The frequency of hormone resistance (HR) was compared in groups of patients.

Results

Among 96 patients with UC, HR was established in 12 (12.5%) patients. In group 1 of UC patients who received less than 1 course of GCS for 12 months for UC exacerbation, patients with HR were 1 (3.3%), in group 2-2 (5.9%) patients with HR, in group 3–9 (28.1%) patients with HR.

When comparing groups 1-st and 2-nd, it was found that the incidence of HR in both patients who received 1–2 courses of GCS for 12 months did not differ (OR-1.813; 95% CI 0.156 - 21.057; p>0.05).

When comparing the 1-st and 3-rd groups showed that the incidence of HR in patients who received 3 or more courses of corticosteroids within 12 months is significantly higher than in patients who received ≤1 course of corticosteroids within 12 months (OR-0.088; 95% CI, 0.010–0.747; p<0.05).

When comparing the 2-nd and 3-rd groups showed that the incidence of HR in patients who received more than 3 courses of corticosteroids within 12 months also has a tendency to a higher risk of development of HR than the patients receiving 2 or fewer courses of corticosteroids within 12 months (OR-0.160; 95% CI, 0.032–0.810; p<0.05).

Conclusion

The frequency of courses of glucocorticosteroid therapy for exacerbation of the disease for 12 months affects the risk of developing hormone resistance in patients with ulcerative colitis.
P519 Impact of skin examination prior to initiation of biological treatment in patients with Inflammatory Bowel Disease: preliminary data
Authors: Hartl C , Novacek G , Reinisch S , Saciri A , Reinisch W , Primas C , Maier H
Published: May 2021

Background

Dermatological affections are common in patients with inflammatory bowel disease (IBD). We aimed to assess if skin examination prior to initiation of biologics in IBD patients would detect relevant skin diseases, such as skin malignancies, which could influence treatment as well as management.

Methods

In this ongoing cohort study we included IBD patients of the Dept. of Gastroenterology and Hepatology of the Medical University of Vienna with indication for biological treatment. Consultants of Dermatology performed a complete dermatological screening prior to initiation of therapy. We recorded all pathological findings, although the focus of this study is on certain dermatoses of high impact (melanoma, non-melanoma skin cancer, hidradenitis suppurativa, pyoderma gangrenosum, erythema nodosum and warts). Furthermore, we used a detailed questionnaire comprised of family history, medication and personal history of IBD. In cases of diagnostic uncertainties we confirmed our differential diagnosis by histopathological and further diagnostic investigations. The descriptive results are given as absolute numbers and percentages.

Results

431 patients were included, 322 patients (74.7%) with Crohn’s disease, 103 (23.9%) with ulcerative colitis and 6 (1.4%) with inflammatory bowel disease unclassified. Melanoma was diagnosed in 3 out of 431 patients (0.7%). Non-melanoma skin cancer was detected in 22 patients (5.2%). Pyoderma gangrenosum, hidradenitis suppurativa and erythema nodosum were present in 5 (1.2%), 12 (2.8%), and 3 (0.7%) patients, respectively. We found viral warts in 73 patients (16.9%). 88 patients (20.4%) received further diagnostic investigations and 302 patients (70.1%) dermatological treatment for the detected skin diseases.

Conclusion

Dermatological screening prior to initiation of treatment with biologics can identify IBD patients with skin malignancies and other high-impact skin diseases. This may influence further IBD treatment as well as management decisions. We conclude that prior dermatological screening is of high importance for safe management of IBD patients with biological therapy.
P527 Investigating fatigue in vedolizumab-treated patients with ulcerative colitis or Crohn’s disease from a Belgian registry
Authors: Louis E , Muls V , Bossuyt P , Colard A , Nakad A , Baert D , Mana F , Caenepeel P , Vanden Branden S , Vermeire S , D’Heygere F , Strubbe B , Cremer A , Setakhr V , Baert F , Vijverman A , Coenegrachts J L , Flamme F , Hantson A , Bennett D , Van Gassen G , Hantsbarger G
Published: May 2021

Background

Vedolizumab (VDZ) has demonstrated remission in ulcerative colitis (UC) and Crohn’s disease (CD), but its impact on patient (pt) fatigue is not well understood. Herein we report interim fatigue analysis data from a Belgian registry of VDZ-treated pts.

Methods

Ad-hoc analysis from the prospective observational Belgian VDZ registry (started, November 2016; data cutoff, February 2019), a sub-study of the European VDZ post-authorization safety study (ENcePP EUPAS6469) included pts aged ≥18 years with UC or CD with ongoing VDZ intravenous therapy (≥2 weeks) at recruitment. At baseline (recruitment) and every 6 months, physicians collected data (follow-up was 3 years or 1 year after last dose if VDZ was discontinued [whichever occurred first] and pts completed the 13-Item Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. Clinical remission was defined as Harvey-Bradshaw Index (HBI) score <5 for CD, and partial Mayo score (pMS) <2 with no individual subscore >1 for UC. This analysis explored the association (using generalized estimating equations) between all available FACIT-F total scores and baseline demographic, clinical, and treatment characteristics in the treatment analysis set (TAS; pts had ≥1 VDZ dose and ≥1 year of follow-up records).

Results

The registry enrolled 202 VDZ-treated UC and CD pts from 19 Belgian centres. TAS included 141 pts (UC 47, CD 94); median follow-up was 537 days; 140/141 pts had ≥1 FACIT-F score. In the UC and CD groups, respectively, 68% and 42% of pts were male; median (IQR) age at index date was 51 (37–59) and 40 (29–52); and baseline median (IQR) FACIT-F total score was 39 (32–46) and 32 (24–40). Lower FACIT-F score (more fatigue) was associated with higher pMS in UC (p<0.001), and higher HBI score (p=0.01) and having ongoing fistulas at baseline (p=0.01) in CD (Table). Less fatigue was associated with being in remission at baseline in both UC and CD (p<0.01). Being male was associated with less fatigue in the overall population and CD (p<0.01), but not in UC alone. Baseline occurrence of extra intestinal manifestations (EIMs) was associated with more fatigue in the overall group (p=0.037); however few pts (UC 4; CD 8) had EIMs. UC pts had less fatigue than CD pts (p=0.004). From baseline to month 24, the change in median (IQR) FACIT-F total score was -3.0 (-12.0 to 5.0) points for UC and 3.5 (-1.0 to 18.0) for CD.

Conclusion

These real-world data from a long-term registry study of VDZ-treated pts in Belgium demonstrate that higher pMS and HBI score, active fistulae, and EIM occurrence at baseline may be associated with more fatigue in IBD pts. Pts treated with VDZ had no significant change in FACIT-F total score over 24 months.
P547 Safety and efficacy of vedolizumab in the treatment of patients with moderate to severe Ulcerative Colitis: a systematic review and meta-analysis
Authors: Khorshid Fasge M , Alboraie M , Abbas W , Sayed Z E , El-Nady M
Published: May 2021

Background

To perform a systematic review and meta-analysis discussing the efficacy and safety of vedolizumab (VDZ) treatment in patients with active moderate to severe ulcerative colitis (UC).

Methods

Using relevant keywords, we searched PubMed, Web of Science, Scopus, and Cochrane Central databases, until June 2020. We included interventional and observational cohort studies which assessed the safety and effectiveness of VDZ 300 mg intravenous infusion, in patients with active moderate to severe UC. We used the Cochrane risk of bias assessment tool and the Newcastle-Ottawa scale to assess the quality of included interventional and cohort studies, respectively. Dichotomous outcomes were pooled as proportion, 95% Confidence interval (CI), and p-value under the random-effects model in the open meta-analyst software.

Results

We found 10 interventional studies and 35 cohort studies, including 4,794 patients eligible for our review. Most of the included citations were single-arm studies. Our meta-analysis showed that VDZ therapy could induce a significant clinical response in UC patients up to 54 weeks (proportion 0.516, 95% CI [0.453, 0.578], p < 0.001). VDZ was associated with clinically significantly clinical remission and steroid-free clinical remission after 54 weeks (p < 0.0001). Durable clinical remission, histological remission, and endoscopic response rates were maintained in UC patients taking VDZ at the 52nd week. There was no significant difference between VDZ and placebo regarding the incidence of drug-related serious adverse events (p = 0.113) and death rates (p = 0.085).

Conclusion

Our systematic review and meta-analysis showed that the use of VDZ in patients with active moderate to severe UC was associated with high percentages of clinical response and remission rates in induction and maintenance treatment stages. VDZ seems to be well tolerated in UC patients, apart from some infections and inflammations. Future RCTs should compare VDZ to active treatments for longer follow-up periods with larger sample size.
P572 The influence of beliefs about medication in therapeutic adherence among patients with inflammatory bowel disease
Authors: De Castro Parga M L , Alvarez-Smith C , Sanroman L , Figueira M , Hernández V , Pineda J , Martinez-Cadilla J , Pereira S , Rodriguez-Prada I
Published: May 2021

Background

Medication nonadherence in inflammatory bowel disease (IBD) is common and has a negative impact on disease outcome. It is currently not clear whether in patients with IBD, the opinions, beliefs and attitudes towards medicines determine an adequate therapeutic adherence. Our aim was to assess what the real influence of medication opinions is on IBD patients adherence.

Methods

Patients attending a tertiary hospital IBD outpatient clinic were enrolled. They filled the BMQ (Beliefs about Medication Questionnaire): a 18-item standardized scale assessing specific opinions about medication that a person is taking and beliefs about the potential for harm and overuse of medication in general. Pharmacy refill data were checked for the previous 3 months and their medication possession ratios (MPR) were calculated. Nonadherence was defined as MPR<0.8.Ethical approval was obtained.

Results

We analyzed 193 IBD patients: 96 women and 97 men with average age 46.1 years. Ulcerative colitis 109 (56.6%) and 84 Crohn′s disease (43.5%). Oral mesalazine was used for IBD control in 48%, immunosuppressnat in 43.5% and targeted therapies, 28.5%. MPR detected non-adherence in 57 patients (29.5%). Patients with CD had a higher adherence than those with UC (78.6 vs 64.2% p=0.03). Non-adherence was higher in patients with mesalazine 41.3% (p=0.001) and lower with targeted therapies 15% (p=0.007). BMQ classified our IBD patients in 60% “ambivalent”, 36% “accepting”, 7% “indifferent” with no “sceptical”: Females had a higher puntuation in BMQ harm about medication scale (p= 0.006). Surgical patients scored higher about the necessity of their IBD medication (0.005) and patients with a low educational level showed many concerns about IBD medication (0.002). Nevertheless there were neither significant differences in BMQ general (abuse/harm) or specific (need/concern) scores nor in attitude profiles between patients with adequate adherence and non-adherent patients.

Conclusion

Non-adherence behaviour in IBD patients was not associated with beliefs about medication. Ulcerative colitis and oral mesalazine were related to lower adherence, meanwhile patients on directed therapies showed high adherence,
P579 Online Education Significantly Improved Gastroenterologists’ Knowledge of Treatment Options and Therapeutic Goals in Ulcerative Colitis
Authors: Bell E , Calle M , Vermeire S
Published: May 2021

Background

With the rapid evolution in treatment strategies and the increasing range of available therapeutics for ulcerative colitis (UC), keeping pace with advances can be a challenge for busy physicians.

We assessed whether online CME can improve gastroenterologists’ knowledge of therapeutic goals and treatment options in UC.

Methods

Gastroenterologists participated in an online CME activity entitled ‘Management of UC: Expert Insights on Current and Emerging Therapies’. This was a 30-minute video roundtable discussion with accompanying slides. Educational effect was assessed using a repeated-pair design, pre-/post-assessment. A Chi-square test of independence determined if a statistically significant improvement (5% significance level, P<.05) existed in the number of correct responses between the pre-test and post-test scores. Cramer’s V estimated the effect size of the education (<.06, modest impact; .06-.15, noticeable impact; .16-.26, considerable impact; >.26, extensive impact). The activity launched on 21 November 2019 with data collection through 4 February 2020.

Results

• Significant improvement in average percentage of correct responses, rising from 67% at baseline to 77% post-activity (P<.001) and noticeable educational impact (Cramer’s V=0.113)

• The percentage of gastroenterologists (n=232) answering all 3 questions correctly rose from 32% at baseline to 55% post-activity

• Significant improvements in knowledge of the minimum therapeutic goal for a patient with moderate-to-severe UC (P<.01) and the VTE risk associated with treatments for UC (P<.01)

• Numerical improvement in knowledge of clinical data from the UNIFI trial for ustekinumab in moderate-to-severe UC

• Almost half (44%) of gastroenterologists indicated improved confidence in their ability to describe clinical data for emerging biologic agents in UC

Conclusion

Online education, delivered as a 30-minute video roundtable discussion among experts, significantly improved gastroenterologists’ knowledge of therapeutic goals and treatment options in UC, which should equip them with the knowledge to make more informed choices for their patients. The success of this online activity, particularly with regard to the impressive improvement in confidence, suggests that gastroenterologists would benefit from further education to reinforce not just their knowledge of clinical data for novel agents but also their confidence in using these new agents to manage patients with UC.
P589 Stable Trends in Radiation Exposure Amongst Patients with a New Diagnosis of Inflammatory Bowel Disease at an Irish Tertiary Referral Hospital
Authors: Matthews T J
Published: May 2021

Background

The utilisation of diagnostic imaging has risen dramatically over time. IBD patients are particularly vulnerable to this inclination.

We evaluated trends in the radiation doses to which our service exposed our new IBD referrals over time.

Methods

Searches of new referrals to our IBD clinic during two 24-month periods beginning 01/06/2005 (n=84) and 01/01/2013 (n=63) were conducted.

The numbers of AXRs, CT APs, Barium Swallows, Meals, Follow-Throughs and Enemas, CT Colonographies and MRI SBs were collated for each patient for the five-year period subsequent to their first attendance. The dataset was irrevocably anonymised. Cumulative effective radiation doses were calculated using estimates provided in leading radiology journals.

Linear regression using the ordinary least squares method examined the relationship between cumulative dose, period of diagnosis, age, gender and category of IBD.

Results

The mean cumulative effective radiation doses for the earlier and later periods were 4.7mSv (95% CI, 1.86 to 7.54) and 7.4mSv (95% CI, 3.60 to 11.26) respectively.

No significant relationship was demonstrated between age (-0.03mSv, 95%CIs: -0.20, 0.12), male gender (0.69mSv, 95%CIs: -4.00, 5.39), or later referral period (3.06mSv, 95%CIs: -1.67, 7.78) and cumulative dose. A diagnosis of Crohn’s (as opposed to UC) had a strongly positive relationship with total radiation dose (5.89, 95%CI: 1.07, 10.70).

12 MRI small bowels were completed during period 2, none during period 1.

Conclusion

Our evaluation shows an upward trend, failing to meet statistical significance, in the radiation doses to which patients with new diagnoses of IBD were exposed to by our service.
P598 Previous Intestinal Resection Is Associated with Postoperative Complications in Crohn’s Disease: A Cohort Study
Authors: Li Y , Duan Y , Zhiyuan Z , Danhua Y
Published: May 2021

Background

To assess the influence of a previous intestinal resection on postoperative complications for Crohn’s disease (CD).

Methods

Data on patients with CD undergoing surgery in our department from January 2016 through December 2019 were retrospectively reviewed. Information collected included demographic details, surgical data, and postoperative outcome. A cross- sectional study design was employed. Associations between postoperative complications and preoperative clinical indicators were further analyzed.

Results

Of the 129 patients with CD studied, 62 patients (48.06%) underwent previous resection. These patients were more likely to be older (P=0:031), have longer disease duration (P=0:025), use less 5-aminosalicylic acid/sulfasalazine preoperatively (P = 0:013), have lower body mass index (P = 0:003), and have a higher American Society of Anesthesiologists (ASA) Physical Status Classification System score (P = 0:043). Patients who had previous surgery had a longer duration of operation (P = 0:003), greater estimated blood loss (P = 0:001), and longer hospital stay (P < 0:001) and were more inclined to develop postoperative complications (P=0:047), particularly anastomotic leak (P=0:021) and severe (Clavien– Dindo grade III/IV) complications (P = 0:038). After multivariate analysis, previous intestinal resection (P = 0:019), preoperative use of steroids (P = 0:026), and ASA score of more than II (P < 0:001) were determined to be the independent prognostic risk factors for postoperative complications. During the 30-day follow-up period, there was no postoperative mortality or readmission.

Conclusion

Previous intestinal resection in patients with CD is an independent predictor of overall postoperative complications.
P680 Similar gut bacterial composition between patients with ulcerative colitis and healthy controls in a high prevalence population: a cross-sectional study of the Faroe Islands IBD cohort
Authors: Á Fríðriksmørk Berbisá M , Rubek Nielsen K , Midjord J , Oddmarsdóttir Gregersen N , Ingham A C , Burisch J , Gratton Vang A
Published: May 2021

Background

The Faroe Islands, a genetically and geographically isolated population in the North Atlantic, has the world’s highest prevalence of inflammatory bowel disease (IBD). Epidemiological studies have characterized this unique cohort, which consists predominately of an ulcerative colitis phenotype, and a decreased risk of developing IBD with emigration. Therefore, the well-characterized Faroese IBD cohort gives the opportunity to better understand the interplay between genetic predisposition and environmental triggers for this complex disease. This study represents the first investigation into the composition of the gut microbiome for the cohort.

Methods

This cross-sectional study consisted of 41 patients with established ulcerative colitis (UC) and 144 age-and sex matched healthy controls (HC) recruited through the Faroese Genome project (FarGen). Participants donated a one-time fecal sample and completed questionnaires on food-frequency, background health and lifestyle. DNA extractions were completed and 16S rRNA amplicon sequencing of the V3-V4 region was performed followed by bioinformatic analysis of taxonomy and diversity metrics.

Results

The overall composition of the sequenced fecal bacteria was dominated by Firmicutes (64,5% of total amplicon sequence variants) and Bacteroidetes (20,95% of total amplicon sequence variants). Akkermansia muciniphila was absent from 30% of the study samples. Discriminatory analysis for indicator taxa identified that Coprococcus and Prevotella_9 characterized healthy controls while genus Ruminiclostridium characterizes UC patients. However, no statistically significant differences were found between UC and HC based on metrics of alpha or beta diversity. Food frequency questionnaires revealed no differences in dietary patterns of the two groups.

Conclusion

The similarity between the microbiome of Faroese UC and HC samples within this study and the absence of the beneficial taxa Akkermansia muciniphila in both groups, raises further questions concerning the underlying susceptibility toward inflammatory and metabolic disorders within this population. This study represents the first 16s rRNA amplicon sequencing data and insights into the Faroese UC and background population. The results highlight the importance of having regionally tuned reference ranges for microbial data.