bluuebunny/crossref_metadata_2025 huggingface dataset:
P347 Undetectable levels of adalimumab in clinical practice: Should we say goodbye to the drug?
Authors: Bejar S , Bastida Paz G , Aguas M , Garrido Marín A , Marques R , Valero Pérez E , del Hoyo Francisco J , Tortosa Seguí L , Muñoz Gómez D , Poveda J L , Nos Mateu P
Published: January 2020

Background

Therapeutic drug monitoring (TDM) is used in inflammatory bowel disease to guide dosing of biologics to individualise drug exposure and optimise outcomes. In case of undetectable levels of Adalimumab (levels <1.6 μg/ml) some authors recommend to discontinue the treatment, although this strategy is not universally accepted. The aim of this study was to describe the evolution (recovery of levels and persistence of treatment) of patients with undetectable levels of ADA and its relationship with the different treatment strategies (dose escalation and/or addition of an immunosuppressant)

Methods

Since October 13 to August 19, 758 TDM were performed in 260 patients treated with ADA. We selected the patients who had at least a level <1.6 μg / ml. Patients with follow-up fewer than 90 days after level detection and those in whom the drug was withdrawn at that time were excluded

Results

We identified 46 patients with undetectable levels; 12 were excluded. Thirty-four patients were included, 29 (85.3%) with Crohn’s disease and 5 (14.7%) with ulcerative colitis. Ten (29.4%) patients had combined treatment and 17 (50%) had previously received another anti-TNF. In 24 (70.6%) TDM was performed proactively. After detection of levels <1.6 μg /ml, ADA was intensified in 20 patients (58.8%) either shortening the interval in 18 (90%), increasing the dose in 8 (40%) or with both interventions in 6 (30%). In 5 (14.7%) patients an immunomodulator was added and in 14 (41.2%) the treatment was not modified. At the end of the follow-up (mean 1101 days; SD 510) 61.8% (21/34) of the patients continued with ADA: 75% (15/20) in the intensified group and 42.9% (6/14) in the group of those who did not receive changes in treatment. Fourteen patients (41. 2%) recovered therapeutic levels (>5 μg/ml), 12 (60%) in the intensified-patient group and 2 (14.3%) in the group in whom the treatment was not modified. ADA was withdrawn in 13 patients (32.8%) after a mean time of 358 days (SD 258). The ADA maintenance rate (HR=3.88; 95% CI 1.2–12.4; p = 0.02) and the recovery ratio of ADA levels (HR = 6.75; 95% CI 1.1–39, 8; p = 0.03) was higher in the intensified group. Hypoalbuminemia was associated with an earlier withdrawal of ADA (p = 0.03)

Conclusion

The intensification of ADA in patients with IBD and undetectable plasma concentrations allows recovery of levels and maintenance of the drug in a high percentage of patients. The decision to withdraw treatment in patients with undetectable levels should be individualised.
P362 Prospective study of phArmaCokinetics of InFliximab during induction in patients with Crohn’s disease and ulcerative colitis (PACIFIC)
Authors: Liefferinckx C , Bossuyt P , Thomas D , Rahier J F , Louis E , Baert F , Dewint P , Pouillon L , Lambrecht G , Vermeire S , Franchimont D
Published: January 2020

Background

Loss of response (LOR) to infliximab (IFX) remains a challenge in routine management of IBD patients. We evaluated IFX high-resolution pharmacokinetics (PK) during induction with intermediate and peak PK levels.

Methods

This is a prospective, multicentre (n = 9), interventional study approved by EC (P2017/484). Fourteen blood samples were collected per patient from baseline to week 30. All patients were IFX naïve with active disease according to clinical, biological and endoscopy criteria. The primary outcome evaluated the inter-individual variability of IFX PK during induction and correlation with remission at week 30. In addition to trough levels (TLs), intermediate (ILs) and peak levels (PLs) were also measured and defined as drug level between two infusions and drug level early on after infusion (+2h), respectively. Remission was defined as having a Harvey Bradshaw Index (HBI) ≤ 4 and C-Reactive Protein (CRP) ≤5 for Crohn’s disease (CD), and as a clinical Mayo score ≤2 and faecal calprotectin <250 µg/g for ulcerative colitis (UC). IFX samples were measured by ELISA (Apdia) while a drug-tolerant affinity capture elution anti-infliximab assay was used to measure anti-infliximab antibodies (ATI) at weeks 6, 22 and 30.

Results

Demographic and baseline data of the study population are presented in Table 1.

Among the 62 patients enrolled, 33.9% of patients (n = 21/62) were in remission at week 30. Eight patients dropped out due to disease worsening. Median TLs at week 6 were higher among patients in clinical remission at week 30 (p = 0.02) confirming previous observations. However, ILs at day 3 as well as PLs after the third infusion were also significantly higher in patients in clinical remission at week 30 (Figure 1a–c).

ATI were detected as soon as week 6. At week 2, infliximab levels were significantly lower among patients in which ATI developed at a later time point (p = 0.006) and this observation was confirmed when measuring ILs at day 17 (p = 0.002), TLs at week 6 (p = 0.002) and ILs at week 10 (p = 0.001).

Conclusion

This multicentre prospective study demonstrates that intermediate levels as early as day 3 predict remission at week 30 in IBD patients. Low IFX levels during induction were correlated to future ATI development. PK modelling may allow to better select patients early on for sustained remission with infliximab.
P366 CRP levels and PMS as early predictors of clinical and endoscopic outcomes in adult patients with moderately-to-severely active UC treated with tofacitinib: a post hoc analysis of OCTAVE Induction 1 and 2
Authors: Dubinsky M C , Hudesman D P , Steinwurz F , Kulisek N , Salese L , Paulissen J , Su C , Ponce de Leon D , Magro F
Published: January 2020

Background

Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). In a Phase 2 study, changes from baseline in C-reactive protein (CRP) levels as early as Week 4 and partial Mayo scores (PMS) as early as Week 2 were shown to correlate with clinical and endoscopic outcomes at Week 8 in patients with UC receiving tofacitinib.1 We aimed to determine whether CRP levels and/or PMS can be early predictors of clinical or endoscopic outcomes at Week 8 in OCTAVE Induction 1 and 2 (NCT01465763; NCT01458951).2

Methods

In OCTAVE Induction 1 and 2, patients received placebo or tofacitinib 10 mg twice daily (BID) for 8 weeks. Mean CRP levels at baseline and Week 4, and PMS at baseline and Weeks 2 and 4, were analysed by secondary endpoint (clinical response, clinical remission, mucosal healing and endoscopic remission) status at Week 8. Univariate logistic regression analyses were performed to evaluate if CRP levels (log-transformed) or PMS were associated with these endpoints.

Results

In patients treated with tofacitinib 10 mg BID, numerically greater decreases from baseline were observed in CRP levels at Week 4 in patients who achieved a clinical response at Week 8 vs. those who did not achieve a clinical response (Table). Similarly, numerically greater decreases from baseline were observed in PMS at Weeks 2 and 4 in patients who achieved clinical response, clinical remission, mucosal healing and endoscopic remission at Week 8 vs. those who did not achieve these endpoints (Table). Logistic regression results showed that PMS at Weeks 2 and 4, and CRP levels at Week 4, were significantly (p < 0.001) associated with a clinical response at Week 8 (odds ratio [95% confidence interval] 0.578 [0.529, 0.631]; 0.483 [0.437, 0.533]; 0.631 [0.572, 0.695], respectively). This was also true for clinical remission (0.523 [0.467, 0.587]; 0.426 [0.367, 0.495]; 0.582 [0.508, 0.666]), mucosal healing (0.650 [0.600, 0.705]; 0.599 [0.548, 0.655]; 0.576 [0.515, 0.643]) and endoscopic remission (0.659 [0.574, 0.756]; 0.604 [0.513, 0.712]; 0.663 [0.549, 0.802]) at Week 8.

Conclusion

These post hoc analyses showed that PMS as early as Week 2 and CRP levels as early as Week 4 may be predictors of improved clinical and endoscopic outcomes in patients with moderately to severely active UC treated with tofacitinib 10 mg BID. These results are in alignment with the findings reported from the Phase 2 trial.1

References
P370 Endoscopic balloon dilatation in paediatric stricturing Crohn’s disease: A retrospective collaborative study of the paediatric IBD Porto group of ESPGHAN
Authors: Ledder O , Viala J , Urlep D , Serban D , De Ridder L , Martinelli M , Romano C , Oliva S , Sharma S , Thomson M , Turner D
Published: January 2020

Background

Endoscopic balloon dilatation (EBD) is an effective management strategy in stricturing Crohn’s disease (CD). While adult studies showed a high success rate of improved symptoms and avoiding surgical intervention, very little has been published in children. We thus present a multi-centre retrospective cohort study of EBD in paediatric CD from 9 centres affiliated with the Paediatric IBD Porto group of ESPGHAN.

Methods

Demographics, imaging, serological data, clinical indices (including the newly-developed modified CD obstructive score (mCDOS)), post-EBD complications and need for surgical intervention were recorded on electronic case report forms.

Results

Thirty-nine balloon dilatations were performed on 34 children (20 (59%) male, mean age 14.3 ± 3.4 years, median disease duration 3.5 years (IQR 1.1–5.8)). Successful avoidance of surgical intervention was recorded in 26 (76%) children, during a median follow-up period of 24 weeks (IQR 8–24). There was an increase in number of patients in clinical remission (wPCDAI < 12.5) following EBD from 20% pre-dilation to 36% (ns), 53% (p = 0.017) and 57% (p = 0.015) at weeks 2, 8 and 24, respectively. There was a trend to reduced mCDOS, from 5 (IQR 0–15) at baseline to 5 (0–6.25) (ns), 5 (0–5) (p = 0.04), and 0 (0–7.5) (ns), respectively. The stricture was primary in 31 (79%) children (17 in the ileocecal valve (ICV) region, 3 in the terminal ileum, 9 in the colon and 1 in the duodenum), 7 of whom had multiple strictures. Eight (21%) children had an anastomotic stricture. Median stricture length was 3 cm (IQR 2–4.7), bowel wall thickness 7 mm (IQR 5–8) and median pre-stenotic dilatation of 4.5 cm (IQR 4–5). Median maximal dilatation diameter was 15 mm (IQR 12–18) with the successful passage of the colonoscope in 26/39 (67%). There were 3 (8%) post-dilatation complications including one bleed following rectal dilatation (with spontaneous resolution) and 2 perforations (1 duodenal perforation managed conservatively and 1 ICV perforation requiring surgical resection).

Conclusion

EBD is an effective and safe technique in paediatric stricturing CD with over 75% avoiding surgery by one year and 8% complications. Further data are required to better identify optimal stricture features and dilatation diameter in children.
P371 Self-medication with analgesics in ulcerative colitis: Results of a patient survey
Authors: Rodríguez-Lago I , Mesonero Gismeno F , Cañas M , Savini C , Saldaña R , Feo-Lucas L , Fernandez S , Cea-Calvo L , Juliá B
Published: January 2020

Background

Ulcerative colitis (UC) is a debilitating chronic condition that affects the large intestine and courses with episodes of flare and remission, being steroid-free remission the main treatment goal. Our aim was to assess the prevalence of self-medication with analgesics, and its associated factors in a Spanish cohort of UC patients.

Methods

An anonymous cross-sectional survey was developed by 3 IBD experts from the Spanish working group on Crohn’s disease (CD) and Ulcerative Colitis (GETECCU), one nurse of the Spanish nursing working group on inflammatory bowel disease (GETEII) and two patients from the Spanish confederation of associations of patients with CD and UC (ACCU). A link to the online survey was distributed to the ACCU affiliates and to other adult patients with UC through 50 inflammatory bowel disease (IBD) units from Spain. Participants voluntarily answered to the survey based on their own experiences during the last year.

Results

We collected data from 546 patients, 61% women, mean age 40 years old. Of these, 51% patients were followed-up by IBD specialists and 47% by a general gastroenterologist. Patients’ self-reported disease activity during the last year was: 125 (23%) inactive, 188 (34%) mild, 170 (31%) moderate and 63 (12%) severe. Visits to the emergency room (24%), urgent telephone calls (43%) and hospital admissions (10%) were reported by patients during the last year. A total of 320 (59%) patients declared to have self-medicated with analgesics during the past year, mostly with paracetamol [n = 247 (45%)] and metamizole [118 (22%)], followed by ibuprofen [26 (5%)] and codeine [23 (4%)]. The frequency of self-medication was higher in those patients who declared having a moderate (57%) to severe (65%) disease activity, compared with those who felt their disease was mild (45%) or inactive (39%), (p < 0.001). In addition, patients who needed urgent telephone assistance showed a higher frequency of self-medication (n = 139, 59%) [OR 2 (95% CI:1–3), p < 0.001]. Multivariate analysis revealed that self-medication with analgesics was associated to female gender [OR 2 (95% CI: 1–3), p < 0.001], intravenous (IV) biological therapy [OR 3 (95% CI: 2–5), p < 0.001] and visits to the emergency room [OR 3 (95% CI: 2–4), p < 0.001].

Conclusion

Self-medication with analgesics is a common practice in patients with UC from Spain. Factors like being a woman, treatment with IV biological drugs, needing urgent telephone assistance and attending to the emergency room, were associated with self-medication with analgesics.

This project was endorsed by GETECCU, GETEII, ACCU and funded by MSD Spain.
P374 Disease course and fate of Crohn’s perianal fistula patients following failure of initial biologic therapy: real-world lessons on the impact of refractory disease from a tertiary centre cohort
Authors: Adegbola S , Mak W Y , Sahnan K , Hiles S , Bassett P , Lung P , Warusavitarne J , Faiz O , Phillips R , Tozer P , Hart A
Published: January 2020

Background

Current evidence demonstrates that anti-TNF therapies lead to clinical response rates >50% have been reported in the short-term. These remission rates decrease to about a third of patients who initially achieved remission, after three years. Options are limited in cases refractory to biologic therapy, and there is limited knowledge of disease course in these cases, in part due to limited disease states characterised for Crohn’s perianal fistula in the absence of cure. This study applies recently described disease states within the context of Crohn’s perianal fistula to determine the fate of patients refractory to initial biologic therapy and quantitatively evaluate the health resource impact of the loss of response to treatment in this cohort.

Methods

Retrospective review of records from patients undergoing anti-TNF treatment for Crohn’s perianal fistula at St Mark’s Hospital between January 2007–December 2016, identified those refractory to treatment. We applied disease states defined from a recent vignette study of the general public and CD patients in the UK, and also obtained data on length of time patients spent in each disease state and subsequent disease states they transitioned to and created a Markov model to assess transition probabilities. We also collected data on healthcare resource utilisation (MRI, hospital interactions, surgical/medical therapy) within each disease state.

Results

Eight fistula disease states (including proctectomy, defunctioning surgery, remission and symptomatic states) were retrospectively ascribed to all clinical records/visits where documentation was available. The majority of refractory patients were switched on to alternate anti-TNF therapy and most reside in a ‘mild chronic symptomatic fistula’ disease state with a minority of patients subsequently transitioning into a severe disease state or remission state. Successful proctectomy disease state accounted for the longest period of continuous length of time in any one disease state (mean 4.4 years). The overall remission rate (of any duration) for our study cohort of 78 patients was 46%; however, sustained (1year or more) remission rate was 27%. Some 19% patients underwent proctectomy. There was considerable healthcare resource utilisation amongst all disease states particularly with biologic therapy (most expensive healthcare resource).

Conclusion

Whereas most patients reside in a mild chronic state following failure of at least one biologic therapy, a fifth of patients refractory to treatment undergo proctectomy which, when successful, accounts for the longest continuous length of time patients spend in a single disease state. There remains considerable healthcare resource utilisation and better treatment options are needed in refractory patients.
P375 Feasibility of the first paediatric randomised controlled pilot trial of faecal microbiota transplant for ulcerative colitis
Authors: PAI N , Popov J , Hartung E , Hill L , Grzywacz K , Godin D , Thabane L , Lee C , Surette M , Moayyedi P
Published: January 2020

Background

The first multicentre paediatric randomised-controlled trial (RCT) of faecal microbiota transplant (FMT) in ulcerative colitis (UC) was recently completed in Ontario and Quebec, Canada. The use of FMT in paediatric UC treatment has been limited to small, open-label case series. Unique clinical and patient factors necessitated a paediatric-specific pilot RCT. Our aim was to assess key feasibility measures of conducting an FMT trial in paediatric patients to inform design, and feasibility of larger, future multicentre studies.

Methods

Patients were randomised (1:1) to receive rectal enemas 2×/week for 6 weeks, followed by a 6-month follow-up period. Enemas contained normal saline (placebo), or RBX2660 (Rebiotix; Roseville, USA), a faecal microbiota preparation of stool from healthy adult donors (active). Patients were eligible for the open-label extension following completion or withdrawal from the placebo arm. Study feasibility was assessed through patient eligibility, recruitment, completion of sample collections, adverse events, and hospitalisations.

Results

Over 36 months across two tertiary IBD clinics, 48 paediatric patients were screened for participation. 75.0% (36) met eligibility criteria for enrolment and 69.4% (25) participated in the randomised trial. 53.8% (7) of patients randomised to the placebo arm entered the open-label arm. We stratified completion of sample collections by intervention (Weeks 0–6), and follow-up phases of the trial (Weeks 6–30). 75.3% of required bloodwork was obtained during both phases; patient-provided stool samples declined from 76.0% (intervention) to 45% (follow-up). 83.0% (10) reported adverse events in the active arm, and 38.4% (5) in placebo; these were all minor and self-limited (muscle pain, cough, fatigue, etc.). No patients experienced adverse events related to enemas. Five patients experienced serious adverse events: IBD flare (2 active, 1 placebo), and reactivation of C. difficile infection (2 active) (Table 1).

Conclusion

In this first paediatric RCT of FMT for UC, we established important feasibility data regarding the design of FMT trials in children. Patient acceptance of FMT was high, and well-tolerated with minor, self-limited adverse events, and few serious adverse events. Return-rates of stool samples were low during follow-up; strategies to improve uptake are needed, particularly given the value of microbiome data for analyses. Overall, our study demonstrates strong interest and tolerance among paediatric patients for FMT-based trials. Future studies will build upon our protocol to enhance clinical data on the effects of microbiota-based therapeutics in children.
P388 Prediction model to safely CEASE anti-TNF therapy in Crohn’s disease: validation of a predictive diagnostic tool for the cessation of anti-TNF treatment in CD in a Dutch population
Authors: Ten Bokkel Huinink S , de Jong D , van der Woude J , Nieboer D , Steyerberg E , Wolfhagen F , van Tuyl B , West R , Romkens T , Tan A , Hoentjen F , Mares W , Bodelier A , Dijkstra G , Mallant R , de Boer N , Reinders J , van Boeckel P , Tack G , Duijvestein M , D’Haens G , de Vries A
Published: January 2020

Background

Tools for patient identification to safely cease anti-TNF therapy in Crohn’s disease (CD) patients are urgently needed. After an individual participant data meta-analysis (IPD-MA) a predictive diagnostic tool has been developed for cessation of anti-TNF therapy in CD. This study aims to validate this tool.

Methods

A retrospective study was conducted, in 16 Dutch Hospitals, of CD patients in whom anti-TNF therapy was ceased. Inclusion criteria were anti-TNF therapy use >6 months, start of anti-TNF therapy due to luminal CD and remission as an indication for cessation. Collected baseline demographic, clinical, biochemical, treatment and imaging data were included; age, gender, smoking, Montreal classification, disease- and remission duration, history of surgery, type of anti-TNF medication, previous or concomitant immunosuppressant, thiopurines level, previous anti-TNF therapy, anti-TNF therapy duration, haemoglobin, leukocytes, thrombocytes, albumin, C-reactive protein, anti-TNF serum concentration, anti-infliximab/adalimumab antibodies, remission at MRI/endoscopy, additional stop reason other than remission. The primary outcome was documented relapse of CD that necessitated (re)introduction of biologicals, corticosteroids or immune-suppressants or surgery.

Results

A total of 523 CD patients (333 females (63%), median age 40 years (IQR 32 – 53)) were included. 293 (56%) patients experienced a relapse after anti-TNF cessation after a median follow-up of 30.2 months (IQR 15–51). The relapse rate was 33% (95% CI 31–34) and 53% (95% CI 52–53) after 1 and 2 years, respectively. The discriminative ability of the prediction model in this external validation cohort (Table 1) equalled that of a previous IPD-MA with a C-statistic of 0.59. An update of the model with faecal calprotectin resulted in a C-statistic of 0.60 [0.55–0.63] and a reported calibration slope of 0.69.

Conclusion

A previously developed predictive diagnostic tool to safely cease anti-TNF therapy in CD has been validated, however, showed moderate performance in this external cohort. A further update of the model with biochemical and histological data is necessary to improve our ability to adequately select patients for cessation of anti-TNF therapy and is currently being performed.
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

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

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 (< 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

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 < 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 < 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

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

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

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 <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

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

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

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 <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.