bluuebunny/crossref_metadata_2025_split huggingface dataset:
P393 Patient and physician perspectives on the management of inflammatory bowel disease: Role of steroids in the context of biologic therapy
Authors: Afzali A , Armuzzi A , Bouhnik Y , Bressler B , Hart A , Rubin D , Sans M , Siegmund B , Sninsky D 
Published: January 2020

Abstract

Background
Corticosteroids are a mainstay of inflammatory bowel disease (IBD) treatment but are not as effective as maintenance therapy and prolonged exposure is associated with significant morbidities. We assessed real-world management of IBD using an international online survey of patients (patients) and physicians and present results related to steroid use for IBD.

Methods
The online survey was conducted in Canada, France, Germany, Italy, Spain, UK, and the USA. The mixed-recruitment methodology was used: patients were recruited by physicians, pt advocacy groups, and panels; physicians were recruited by recruitment agencies and panels. Eligible patients were adults with Crohn’s disease (CD) or ulcerative colitis (UC) (targeted 1:1 ratio CD:UC) who had received IBD treatment but had not had surgery for UC. Eligible physicians were gastroenterologists who had treated ≥12 CD patients and ≥12 UC patients (≤70% with a disease of mild severity) in the prior month and were responsible for treatment decisions.

Results
Surveys were completed by 2398 IBD patients (1368 CD, 1030 UC) and 654 physicians. Mean ages were 43 y and 45 y for patients with CD and UC, respectively; 60% and 55% were female. Most patients (93% CD, 78% UC) had moderate/severe IBD per clinical criteria; 71% and 47%, respectively, had ever required hospitalisation. Physicians had a mean monthly caseload of 42.9 CD patients and 43.3 UC patients, and 62.4%–67.2% of their IBD patients had moderate/severe disease. Biologic therapy was currently used by 50% of CD patients and 32% of UC patients, consistent with results for physicians (54% CD, 43% UC). Most patients (69% CD, 58% UC) reported a loss of response (LOR) to prior treatments, and most physicians reported that their patients experienced a LOR to biologic therapy fairly/very frequently (66% CD, 56% UC). Approximately 75% of IBD patients had ever used steroids for their IBD; steroid use of ≥4 or ≥6 months in the past year was reported by 35% and 18% of CD patients, respectively, and by 40% and 19% of UC patients. Physicians reported that 40% and 14% of their IBD patients used steroids for ≥4 or ≥6 months in the past year. Among patients currently receiving steroid therapy, many (48% CD, 42% UC) were concerned about any steroid use, and two-thirds reported wanting to stop steroid treatment as soon as the disease was under control. Only 27% of physicians reported a concern about any steroid use; approximately half reported a concern about ≥4 months of steroid use per year.

Conclusion
This international survey demonstrated that steroid use is prevalent and LOR to biologics is common among moderate/severe IBD patients. There were differences in pt and physician perception of steroid use; many physicians believed ≥4 months of steroid use per year was not a concern. A significant unmet need remains for treatments that provide sustained control of IBD.
P403 Post hoc examination of VISIBLE 1 data for baseline predictors of response to 2 or 3 IV doses of vedolizumab for adults with moderate-to-severe ulcerative colitis
Authors: Sandborn W , Loftus E V , Baert F , Jansson J , Chen J , Candela N , Lasch K , Kisfalvi K 
Published: January 2020

Abstract

Background
Vedolizumab (VDZ) is a gut-selective α 4β 7 integrin monoclonal antibody approved for IV administration for moderate to severe ulcerative colitis (UC). The phase 3 VISIBLE 1 study evaluated SC VDZ for UC maintenance therapy. After 2 IV doses, 56.1% patients had a clinical response at week 6; among patients who received a third induction infusion, clinical response rates were 79.7%. In this post hoc analysis, we examined baseline characteristics as predictors of clinical response to IV induction with VDZ.

Methods
In the VISIBLE 1 study (NCT02611830; EudraCT 2015-000480-14), patients (patients) received IV VDZ 300 mg at Weeks 0 and 2. At Week 6, clinical responders were randomised to maintenance SC therapy; nonresponders were given a third IV dose and reassessed at Week 14. As endoscopy was only available at Week 6, the clinical response at Week 6 was defined as ≥3 points and ≥30% reduction in complete Mayo score from Week 0 and at Week 14 as a ≥2 points and ≥25% reduction in partial Mayo score from Week 0. Both definitions also included an accompanying decrease in rectal bleeding subscore ≥1 or absolute subscore ≤1.

Results
Overall, 383 patients received ≥1 dose of IV VDZ. Of these, 56.1% responded at Week 6 after 2 VDZ doses. Of the 143 patients who received 3 IV doses, 79.7% responded at Week 14. No clinically meaningful differences in baseline demographic and disease characteristics were observed between patients who responded after 2 or 3 IV doses (Table). Differences in disease location and partial Mayo score (&lt; or ≥6) were observed between the responders and nonresponders in the 3 IV dose group. Baseline characteristics were evaluated descriptively to assess predictors of clinical response after 2 or 3 IV VDZ doses.

Conclusion
Clinical response was achieved by most patients after either 2 or 3 IV VDZ infusions in the VISIBLE 1 trial. Post hoc analyses revealed no clinically meaningful differences in baseline characteristics or disease characteristics that could serve as predictors of response following 2 or 3 VDZ infusions. Further real-world experience may elucidate potential predictors of response to VDZ.
P408 Long-term impact of the decrease of infliximab trough levels on the disease course in Inflammatory Bowel Disease patients under maintenance treatment with infliximab
Authors: Orfanoudaki E , Gazouli M , Foteinogiannopoulou K , Theodoraki E , Legaki E , Koutroubakis I 
Published: January 2020

Abstract

Background
The measurement of infliximab trough levels (IFX-TLs) has been suggested as an important biomarker for the optimisation of treatment in patients with inflammatory bowel disease (IBD). We have previously reported that IFX-TLs of patients under maintenance treatment with IFX show decreasing patterns associated with an increasing pattern of CRP levels1. We aimed to study the clinical impact of this observation by recording the treatment changes that became necessary during a three year follow-up.

Methods
Consecutive asymptomatic patients on maintenance treatment with IFX were included. Two different measurements of IFX-TLs were made (ELISA, Eagle BioSciences) with a ten-month interval using serum samples drained before IFX infusion. After the second measurement patients were followed up for three years and all treatment modifications including IFX intensification, change of biologic agent or IBD-related surgical intervention were assessed.

Results
Among a total of 86 IBD patients under maintenance treatment with IFX, 64 [49 CD, 15 UC, 42 men, mean age 44.2 ± 15.2 years, 41 in combination therapy with immunomodulator, 6 in intensified dose], with 2 available measurements of IFX-TLs (A and B) were included in the study. Median levels of IF-TLs were 5.07 (IQR 1.60–12.73) μg/ml in measurement A and 4.68 (1.19–7.83) μg/ml in measurement B (p &lt; 0.0001). Treatment was intensified in 8 patients after measurement A. Patients with stable IFX dose showed a significant reduction in median IFX-TLs from 5.65 to 3.8 μg/ml (p &lt; 0.0001). Moreover, CRP levels were significantly increased in measurement B compared with measurement A [0.33 (03–4.4) mg/dl vs. 0.31 (0.3–3.8) mg/dl, p = 0.02]. During a 3 year follow-up, 22 (34%) patients needed treatment optimisation (6 IFX intensification, 7 change of agent, 6 surgery, 3 change of agent plus surgery). In three patients IFX was stopped for safety reasons. Fifty-eight hospitalisations in 19 patients were also recorded. The decrease of IFX-TLs between the two measurements was significantly more in patients with treatment optimisation compared with patients without treatment optimisation (p = 0.03).

Conclusion
IBD patients who are on maintenance treatment with infliximab showing decreasing patterns of IFX-TLs often need treatment optimisation during the follow-up due to clinical or endoscopic activity. These results probably suggest the importance of the proactive therapeutic drug monitoring and early treatment optimisation in these patients

References
P412 Maintenance therapy of vedolizumab (VDZ) after induction of remission by tacrolimus (TAC) in patients with refractory ulcerative colitis (UC)
Authors: Ito A , Shun M , Teppei O , Katsutoshi T 
Published: January 2020

Abstract

Background
The number of patients with ulcerative colitis (UC) is increasing. As the number of patients increases, patient backgrounds become diverse, and treatment choices that match the background are required. Most UCs are mild, but about 30% are more than moderate. UCs with moderate or higher illness have resistance/dependence to steroids and are difficult to introduce remission. In recent years, many new drugs have appeared for remission induction therapy. However, in UC treatment, maintenance therapy that suppresses relapse after induction of remission is important. Maintaining long-term remission prevents deterioration in the quality of life and reduces the incidence of UC-related colorectal cancer. To that end, it is important to consider remission maintenance therapy. In patients with intractable UC who have been in remission with tacrolimus (TAC) and used vedolizumab (VDZ) as maintenance therapy, patient background, relapse rate (observation period 181.5 ± 25.9 days), (3) safety of TAC and VDZ combination The sex was examined.

Methods
Seven patients who received remission with TAC and maintained remission with VDZ between November 2018 and June 2019 were included. (1) Patient background at the time of introduction of TAC and VDZ, TAC administration period (day) until the start of VDZ, (2) Relapse rate, (3) AZA use history, side effects, and adverse events caused by the combined use of VED.

Results
(1) Patient background was age at TAC introduction (age) 44.4 ± 19.7, sex (male / female) 3/4, disease duration (year) 12 ± 11.5, CAI 14.4 ± 2.9, Hb 11 ± 0.8, CRP 5.5 ± 3.6, Endoscopic score (Mayo 3 ± 0, UCEIS 7 ± 1.1), CAI at the time of VDZ introduction 6 ± 3.3, Hb 11.3 ± 2.0, CRP 0.4 ± 0.5, TAC administration period until VDZ start 140 ± It was 155. (2) Six patients had a history of AZA use. 4 out of 6 cases with AZA history side effect due to AZA was observed. The side effects of AZA were leukopenia in 2 cases, headache in 2 cases, and liver injury in 1 case. (There were duplicate cases) (3) No adverse events were observed due to the combined use of TAC and VDZ.

Conclusion
TAC has clinical remission or symptom improvement for refractory UCVDZ had been administered since then. In cases where administration of AZA was difficult, VDZ was selected as maintenance therapy. There were no serious side effects from the combined use of TAC and VDZ. TAC is a drug that has a rapid effect. However, long-term administration of TAC is at risk for kidney damage. Therefore, we considered that maintenance therapy with VDZ after TAC is effective.
P416 Results of the first paediatric randomised controlled trial of faecal microbiota transplant for ulcerative colitis
Authors: Pai N , Popov J , Hill L , Hartung E , Grzywacz K , Godin D , Thabane L , Lee C , Khan W , Surette M , Moayyedi P 
Published: January 2020

Abstract

Background
The role of faecal microbiota transplant (FMT) for the treatment of ulcerative colitis (UC) has been reported across 4 randomised-controlled trials (RCT) in adults. Promising data have emerged from small, open-label paediatric case series and case reports but a proper blinded, placebo-controlled RCT has not been described in children. We report results from the first multicentre RCT of FMT in paediatric UC patients, conducted over 36 months in Ontario and Quebec, Canada.

Methods
We enrolled 25 children, ages 4–17 years old with active UC across two tertiary IBD clinics. Patients had active inflammation and remained on stable doses of medication at entry. Blinded participants received enemas containing healthy donor stool (active) or normal saline (placebo), 2×/week for 6 weeks. Faecal calprotectin (fCal), C-reactive protein (CRP), and paediatric ulcerative colitis activity index (PUCAI) scores were compared between groups during intervention, and at four follow-up time points over 30 weeks. Donor and recipient stools were measured for 16s rRNA and metagenomics analyses.

Results
In intention-to-treat (ITT) analysis, FMT (n = 13) at 6 weeks was more likely to improve clinical response (OR 9.3, 95% CI [0.7, 122.6]), CRP (OR 4.7, 95% CI [0.8, 28.4]), and fCal (OR 13.3, 95% CI [1.1, 166.4]) from baseline compared with placebo (n = 12). FMT at 30 weeks was also more likely than placebo to improve clinical response, CRP, and fCal (Table 1). In ITT analysis of the open-label arm (n = 7), FMT at 6 weeks and 30 weeks decreased CRP (−42.9%, −28.6%), fCal (−28.6%, −42.9%), and PUCAI score (−14.3%, −42.9%) from baseline.

Conclusion
Serial FMT enemas containing healthy donor microbiota led to greater improvements in serum and stool inflammatory markers, and rates of clinical response, in paediatric patients with active UC compared with placebo. These improvements largely persisted beyond 6 months after final FMT treatment. This study offers the strongest preliminary evidence, from a blinded, placebo-controlled multicentre RCT for the role of FMT in the management of paediatric UC.
P417 Do ACE inhibitors and angiotensin II receptor blockers improve disease outcomes in inflammatory bowel disease?
Authors: FAIRBRASS K , Hoshen D , Ford A C , Gracie D 
Published: January 2020

Abstract

Background
The renin-angiotensin system (RAS) has an established role in the pathogenesis of fibrosis and inflammation in renal and cardiovascular disease. High concentrations of angiotensin-converting enzyme (ACE) and renin are found in the small and large bowel. This is elevated further within inflamed colonic tissue of inflammatory bowel disease (IBD) patients, compared with controls. (1) ACE inhibitor (ACEi) or angiotensin II receptor blocker (ARB) therapy may inhibit the effects of RAS in IBD. We aimed to examine the relationship between ACEi/ARB use and longitudinal disease activity outcomes in patients with IBD.

Methods
In a well-characterised cohort of IBD patients, followed up for a minimum of 2 years, baseline demographics and longitudinal disease activity were compared between patients using ACEi/ARB and those not. We reviewed case notes for flare or glucocorticosteroid use, escalation of medical therapy, hospitalisation, and intestinal resection. In univariate analyses, the χ² test was used to compare categorical variables and independent samples t-test for continuous data. A P value of &lt;0.05 was considered statistically significant. Multivariate Cox regression analyses were expressed as hazard ratios (HR) with 95% confidence intervals (CI).

Results
In total, 764 patients with IBD (UC = 321, CD = 443) were included. There was no significant difference in baseline demographics (sex, ethnicity, and smoking) between those with ACEi/ARB use or non-use. Mean age was higher in those taking ACEi/ARBs (60 ± 13 vs. 41 ± 16). Univariate analyses showed a trend towards improved outcomes in those using ACEi/ARB, which was significant for intestinal resection (Table 1). Following multivariate Cox regression analysis, a continued trend of improved outcomes with ACEi/ARB use was observed (Graphs 2 and 3).

Conclusion
These data show a trend towards improved longitudinal disease activity outcomes in IBD patients using ACEi/ARBs. The study may be underpowered to detect a significant difference in these comparisons. Future studies performed in larger cohorts, with longer follow-up may yield significant results.

Reference
P424 Economic evaluation of vedolizumab SC for the treatment of moderate-to-severe ulcerative colitis in Canada
Authors: FISCHER A , Oppe M , Stypa S , Lukyanov V , Petrakis I 
Published: January 2020

Abstract

Background
Vedolizumab intravenous (IV), a gut selective humanised monoclonal antibody, is indicated for the management of moderately to severely active Ulcerative Colitis (UC) and has been shown in the only head-to-head clinical trial within UC to be superior to adalimumab (NCT02497469). Furthermore, the novel vedolizumab subcutaneous (SC) has recently been proven to be an effective treatment of UC (NCT02611830). The objective of this study is to estimate the comparative cost-effectiveness of vedolizumab IV with updated efficacy data, and vedolizumab SC for the first time. Both vedolizumab IV and SC have been compared with other publicly reimbursed biologics for the treatment of patients with moderate-to-severe UC from a Canadian public healthcare payer perspective.

Methods
A hybrid decision tree/Markov model was developed to simulate the clinical course of UC, translating the disease course into costs and quality-adjusted life-years (QALYs). Comparative efficacy of vedolizumab SC, vedolizumab IV, adalimumab, infliximab IV, and golimumab were sourced from a network meta-analysis. Drug and disease management costs (2019 $CAD) were sourced from Ontario public payer schedules of benefits. Utilities were sourced from the literature. Clinical and economic outcomes were projected over a lifetime and discounted at 1.5% annually.

Results
Within a mixed bio-naïve/experienced population, vedolizumab SC resulted in slightly more QALYs than vedolizumab IV and dominated adalimumab (Table 1); vedolizumab SC yielded an incremental cost-effectiveness ratio (ICER) of $CAD 6,727 per QALY and $CAD 52,673 per QALY relative to golimumab and to infliximab (for which the price of a biosimilar was used), respectively. Further scenario analysis within bio-naïve populations supported the robustness of the base-case results, demonstrating that vedolizumab SC or vedolizumab IV were either dominant or cost-effective across all scenarios.

Conclusion
Our analysis suggests that vedolizumab SC and vedolizumab IV are a cost-effective therapeutic alternative relative to other biologics for moderate-to-severe UC in Canada. Future research will expand the analysis across all biologic comparators as they are used in the real world.
P435 Real-world clinical outcomes after elective discontinuation of first-use biologics in IBD patients
Authors: Shivaji U N , Bazarova A , Critchlow T , Nardone O M , Smith S C , Love M , Davis J , Ghosh S , Iacucci M 
Published: January 2020

Abstract

Background
In real-world clinical practice, biologics may be discontinued due to variety of reasons, including discontinuation by gastroenterologists, in the UK. The aim of the study was to report on outcomes after discontinuation in IBD patients after a minimum follow-up of 24 months.

Methods
All IBD patients who discontinued their first-use biologics between January 2013 and Dec 2016 were identified from the EMR at a tertiary referral centre to ensure at least 24 months follow-up. Reasons for discontinuation and pre-defined adverse outcomes (steroid and other rescue therapies, hospitalisations, surgery including perianal) were recorded. The data were analysed using multivariable and univariable logistic regressions within a machine learning technique in order to predict adverse outcomes within the stated timeframe. We performed Kaplan-Meier survival analysis for those patients who had biologics electively discontinued.

Results
In total, 147 IBD patients who discontinued biologics (M = 74.median age 39 years; CD = 110) were identified. Follow-up ranged from 24 to 60 months (median 40 months). One hundred and forty-four patients (98%) discontinued anti-TNF (1% biosimilar anti-TNF and 1% vedolizumab) and 69 (47%) were on thiopurines at start of biologics. Fifty-nine patients (40%) had biologics electively discontinued by their gastroenterologists and they were analysed separately. Of the 59 elective discontinuations, 22(37%) continued thiopurines after biologic stoppage; 37/59 (63%) patients had at least one adverse outcome (AO) within 6 months of discontinuation and 42/59 (71%) patients restarted biologics.

Conclusion
The majority of patients who electively discontinued biologics had IBD-related AO rapidly after the stoppage and needed to restart biologics. Almost all patients had AO by the end of the study follow-up period. This should be discussed with patients when considering discontinuation of biologics.
P437 Anti-TNF α antibodies in patients with inflammatory bowel disease naive to anti-TNF therapy treated with biosimilar infliximab (CT-P13): a prospective single-centre real-life study
Authors: Filip R , Pękala A , Jarmakiewicz-Czaja S 
Published: January 2020

Abstract

Background
There are several tests for detecting antibodies to infliximab. The tests differ in sensitivity and therefore the detection of antibodies varies significantly between clinical trials, and less data is available for induction compared with the maintenance therapy.
The aim of the study was to determine the incidence of anti-drug antibodies (ADAs) in patients during induction and maintenance therapy using the Enzyme-Linked Immunosorbent Assay (ELISA) and to analyse the risk factors for their occurrence.

Methods
It was a prospective single-centre study involving 84 patients with IBD during treatment with biosimilar infliximab (CT-P13) at the Tertiary IBD Center in South-eastern Poland between 2016 and 2019. All participants were naive to previous anti-TNF α therapy (80 patients). ADAs serum testing was only performed when IFX levels below 3 µg/ml were found during induction or maintenance therapy. The incidence of ADAs was analysed, and the relationship between the presence of ADAs and selected variables was assessed: gender, type of disease, immunosuppressive therapy, and undetectable drug level at week 6. The relationship between response to induction treatment and high//low ADAs titers was also compared using Fisher’s exact test.

Results
The incidence of ADAs in the study population was 10.7%, which is 20.4% of patients with non-therapeutic and 50% of patients with undetectable levels of IFX. The percentage of people with ADAs in the induction treatment group was 11.3% (n = 6) and in the maintenance group 3.9% (n = 3). There was no statistically significant difference in the frequency of finding ADAs in both groups (p = 0.158). In contrast, a statistically significant relationship between the undetectable level of IFX at week 6 and the presence of ADAs was confirmed, 88.9% of patients with ADAs vs. 16.0% patients without ADAs (p &lt;0.001. Comparison of the relationship between response to induction treatment and high//low ADAs titers did not show a statistically significant relationship between these variables (p = 0.381).

Conclusion
The overall incidence of ADAs in patients treated with biosimilar infliximab (CT-P13) naive to previous anti_TNF therapy was relatively low, but in the case of undetectable levels of the drug, the phenomenon of immunogenicity was detected in half of the patients. Undetectable level of infliximab at week 6 was a risk factor for the presence of ADAs. There was no significant association between response to induction therapy and ADAs titers.