bluuebunny/crossref_metadata_2025_split huggingface dataset:
P463 Induction of endoscopic response: a network meta-analysis of induction studies comparing ontamalimab with other treatments for moderate-to-severe ulcerative colitis
Authors: Vickers A , Nag A , Devine B , Sands B E , Panaccione R , Peyrin-Biroulet L , Danese S , Vermeire S , Gorelick K J , Goetsch M , Hartley L 
Published: January 2020

Abstract

Background
Clinicians, patients, payers and policymakers require relevant, high-quality evidence to support decision-making regarding the treatment of ulcerative colitis (UC). In the absence of head-to-head trials, network meta-analysis (NMA) can be used to compare treatments. We conducted an NMA to compare the efficacy of ontamalimab (anti-MAdCAM-1) using its phase 2 data, with all biologics and novel small molecules for which induction study data on endoscopic response were available.

Methods
A systematic literature review was conducted in November 2017 to identify published randomised controlled trials of induction treatment in patients with moderate-to-severe UC. An NMA of the identified studies was performed using random-effects models and methods based on NICE guidance. Odds ratios and 95% credible intervals were calculated to describe the relative differences between treatments and placebo in terms of efficacy in inducing endoscopic response. Results were examined by anti-TNF status (naïve vs. experienced).

Results
In total, 15 phase 2 and phase 3 induction studies of the following agents were available and included: adalimumab (160/80mg), etrolizumab (100mg and 300mg), golimumab (200/100mg), infliximab (5mg), ontamalimab (22.5mg and 75mg), ozanimod (0.5mg and 1mg), tofacitinib (10mg) and vedolizumab (300mg). The definition of endoscopic response (improvement) in all trials was a Mayo endoscopic subscore of ≤1. Homogeneity between studies was good, enabling pooling of results. Figure 1 shows odds ratios for induction of endoscopic response with treatments relative to placebo in anti-TNF-naïve and -experienced patients. All treatments performed significantly better than placebo in anti-TNF-naïve patients, with the exception of both doses of etrolizumab and ozanimod 0.5 mg. Significant differences between some treatments were observed; specifically, ontamalimab 22.5 mg (p = 0.0277), tofacitinib 10 mg (p = 0.0233) and infliximab 5 mg (p = 0.0047) were all superior to adalimumab 160/80 mg.

Conclusion
This study suggests that ontamalimab, infliximab and tofacitinib could be superior to adalimumab in inducing endoscopic healing, although it was conducted before any large-scale head-to-head trials of these drugs. Furthermore, large variances due to differing endpoint timings, the combination of phase 2 and phase 3 data, and lack of control for placebo response rates preclude firm conclusions being drawn.
P464 Vedolizumab concentrations in colonic mucosal tissue of ulcerative colitis patients inversely correlate with the severity of inflammation
Authors: Van den Berghe N , Verstockt B , Gils A , Ferrante M , Vermeire S , Thomas D 
Published: January 2020

Abstract

Background
Multiple studies have reported the association between vedolizumab serum concentrations and endoscopic outcomes in patients with ulcerative colitis (UC). However, little is known about drug consumption in tissue and the relationship with mucosal inflammation. This study aimed to investigate vedolizumab concentrations in the tissue of UC patients and the correlation with their inflammatory state and serum levels.

Methods
A paired serum sample and colonic mucosal biopsy were collected in 36 UC patients at week 14 of vedolizumab treatment. In non-responders, defined as a Mayo endoscopic subscore of ≥2, inflamed colonic biopsies were taken in the sigmoid around 20–30 cm from the anal verge. In responders, defined as a Mayo endoscopic subscore ≤ 1, a biopsy was taken in a macroscopically uninflamed area at the same location. Biopsies were lysed by the addition of 10 μl lysis buffer (50 mM Tris, 0.1% Triton X-100 and 100 mM NaCl) per mg tissue and vortexed every 5 min during 1 h. Total protein content was measured and normalised to 3 mg/ml before analysis of the vedolizumab concentration using an in-house developed ELISA. Results are expressed as µg vedolizumab/mg total protein content.

Results
A positive correlation was observed between vedolizumab concentrations in tissue and serum (Spearman r = 0.8447, p &lt; 0.0001), both in inflamed (r = 0.8609, p &lt;0.0001, n = 16) and uninflamed tissue (r = 0.7925, p &lt;0.0001, n = 20). The median tissue vedolizumab concentration in patients with Mayo endoscopic subscore 0, 1, 2 and 3 were 0.120, 0.074, 0.062 and 0.064 μg/mg, respectively (p &lt; 0.01, see figure), indicating that tissue drug levels inversely correlate with the severity of inflammation. Vedolizumab tissue concentrations were significantly lower in non-responders compared with responders (0.064 vs. 0.112 μg/mg, p &lt;0.05). Moreover, patients achieving Mayo endoscopic subscore 0 had significantly higher vedolizumab levels in colonic tissue compared with patients not achieving this outcome (0.120 vs. 0.065 μg/mg, p &lt;0.02). Interestingly, a trend was observed towards higher serum-to-tissue ratios of vedolizumab in non-responders compared with responders (p = 0.0523). This finding suggests that if two patients have the same serum vedolizumab concentration, the patient with mucosal inflammation is more likely to have lower tissue levels than the patient with no or limited inflammation.

Conclusion
Vedolizumab concentrations in colonic mucosal tissue of UC patients inversely correlate with the severity of inflammation. As the serum-to-tissue ratio of vedolizumab is numerically higher in non-responders compared with responders, the relative distribution of vedolizumab in serum and tissue might be more important than the drug concentration alone.
P465 Therapeutic drug monitoring in Crohn’s disease patients, a comparison between homogeneous mobility shift assay and point of care method
Authors: Bodini G , Demarzo M G , Djahandideh A , Baldissarro I , Savarino E , Savarino V , Jain A , Risso P M , Giannini E G 
Published: January 2020

Abstract

Background
Therapeutic Drug Monitoring (TDM) is a useful tool to help physicians managing patients with Inflammatory Bowel Disease treated with anti-tumour necrosis factor (TNF) drugs. Different techniques are available to evaluate serum drug concentration (TL), However, these techniques are time-consuming. A point-of-care (POC) method has been proposed to evaluate drug TL and overcome the limitations inherent to other methodologies. Our aim was to evaluate the capability of POC to discriminate between IBD relapse and remission and to evaluate the concordance of drug TL measured with POC and HMSA

Methods
We analysed with Quantum BlueÒ (Buhlmann Laboratories AG, Schonenbuch, Switzerland) (POC) 200 Adalimumab (ADA) and 200 Infliximab serum samples of 46 Crohn’s disease (CD) patients previously assessed with HMSA. Blood samples were drawn at standardised time points during anti-TNF treatment (2, 6, and every 8 weeks), before anti-TNF administration. Disease activity was assessed by the Harvey–Bradshaw Index (HBI, remission defined by HBI&lt;5).

Results
We evaluated 46 CD patients responders to anti-TNF induction with ADA (n = 25, 54.3%) and IFX (n = 21, 45.6%) with a median follow-up of 83 weeks (range 16–144 weeks). At week 16, median ADA TL of patients in remission were significantly higher as compared with patients in disease relapse using both HMSA [12.7 μg/ml (range, 8.9–23.6 μg/ml) vs. 6.6 μg/ml (range, 0.7–9.6 μg/ml), p = 0.0001] and POC [17.8 μg/ml (range 7.6–35.0 μg/ml) vs. 9.8 μg/ml (range 5.8–11.4 μg/ml), p = 0.0003]. The concordance between the two different techniques has been assessed as 0.76 by Choen Kappa. Considering IFX TL, patients in remission had higher serum drug concentration using both HMSA [7.0 μg/ml (range, 0.0–21.8 μg/ml)] and POC [6.2 μg/ml (range 0.4–14.3 μg/ml)] as compared with patients who experienced disease relapse [HMSA, 0.1 μg/ml (range, 0.0–4.1 μg/ml), p = 0.019; POC, 0.45 μg/ml (range 0.4–3.3 μg/ml), p = 0.0072]. The concordance between the two different test for IFX TL was 0.81. We obtained similar results at the end of follow-up: median ADA TL was higher in remission than in disease relapse patients using both HMSA and POC [p = 0.001 and p = 0.0012] with a concordance of 0.75. Median IFX TL was higher in remission than in disease relapse patients using both HMSA and POC (p = 0.13 and p = 0.25) with a concordance of 0.70.

Conclusion
Both POC and HMSA are TL tests able to differentiate relapse and remission in IBD patients. The association between anti-TNF TL and disease status (remission/relapse) was better in ADA-treated patients rather than patients treated with IFX. Finally, we demonstrated a good concordance between HMSA and POC. Anti-drug antibody concentrations while available on HMSA were not available on POC
P468 Switching from adalimumab originator to ABP 501 biosimilar: a multicentre North Italian study
Authors: Barberio B , Melatti P , Zingone F , Bertani L , Ferronato A , GUBBIOTTI A , Massimi D , D’Incà R , Savarino E V 
Published: January 2020

Abstract

Background
In late 2018, adalimumab (ADA) biosimilars have been approved by the EMA with the same indications of the reference product (RP), that is Humira. However, while their efficacy and safety have been proven in patients with rheumatoid arthritis and psoriasis showing no differences compared with the RP, data on inflammatory bowel disease (IBD) is lacking. The primary aim of this study was to verify the ability of ABP501 to maintain the clinical response induced by the RP after switching to the biosimilar.

Methods
We retrospectively enrolled all consecutive patients who switched to ABP501 by ADA Originator at the IBD Units of Veneto Region (Padua, Santorso) from December 2018 to November 2019. We collected data on partial Mayo (p-Mayo) Score, Harvey–Bradshaw Index (HBI), C Reactive Protein (CRP), faecal calprotectin (FC), concomitant steroid and azathioprine therapy at the time of the switch (T0) and after six months. Continuous and categorical variables were expressed as mean with standard deviation (SD) and frequency with percentages respectively. Comparisons among variables were conducted using one-way ANOVA and chi-square. Data were analysed using STATA11 software.

Results
Forty IBD patients switched to biosimilar [7 with ulcerative colitis (UC) and 33 with Crohn’s disease (CD)] were included in the study. All switched patients were in remission or in mild clinical activity at the time of the switch. We observed a clinical worsening and clinical improvement in 8 and 2 patients, respectively (p = 0.001) from T0 to T1. FC value increases at T1 compared with T0 (from a mean value of 98.32 to 137.9 μg/g) but without significant difference. Seven patients needed to add steroids at T1 (p = 0.04) and five (12.5%) needed therapeutic optimisation. Finally, 8 (20%) patients stopped therapy: 7 for loss of response and 1 for an adverse event.

Conclusion
Our data show that after switching, one out of three of the patients may experience disease relapse, requiring treatment optimisation (i.e. addiction of steroids or increasing the dose to once a week) or treatment discontinuation. Thus, patients should be strictly observed in order to prevent or, at least, early manage such clinical relapses. Larger and longer studies are mandatory to understand the clinical implications of these findings.
P469 Stay in class or switch out of class after anti-TNF failure in inflammatory bowel disease (IBD). Real-world data from a large district general hospital
Authors: Johnson H , Vythilingam S , McLaughlin S 
Published: January 2020

Abstract

Background
Biosimilar infliximab (IFX) and adalimumab (ADA) are well-proven cost-effective anti-TNF drugs in IBD; in our practice, the majority of patients with IBD receive IFX or ADA first line. Since the introduction of Vedolizumab (VED) and Ustekinumab (UST) some have recommended switching out of class after failing a single anti-TNF. This practice has significant cost implications. To establish the outcome of treatment response in patients treated with a second anti-TNF agent after anti-TNF failure compared with the outcome of patients treated with VED and UST after anti-TNF failure.

Methods
We maintain a prospective IBD database. We searched our database for the outcomes of patients who failed their first anti-TNF drug but were in a clinical remission 6 months after changing to a second or third biologic drug. Disease type, age, gender and response to their second and third biologic drug were recorded. Clinical remission was defined as off steroids with calprotectin &lt;250 and no symptoms of active IBD.

Results
Two hundred and eighty-seven patients were identified. One hundred and forty (48.8%) were male. Mean age was 43.2 (range 18–94). Disease type was 75 (26%) UC, 210 (73.2%) CD, 2 (0.7%) IBD-U. One hundred and ninety-three patients received IFX 1st line, 118 (40%) failed. Of these 84 (72%) received ADA, 28 (24%) VED and 6 (5%) UST second line. Remission with second-line treatment was achieved in 58 (69%); ADA, 18 (64%); VED, 6 (100%); UST. Remission with third line treatment; was achieved in 6 (100%); VED; 5 (100%); UST. Ninety-four patients received ADA 1st line, 33 (35%) failed. Of these 11 (33%) received IFX, 10 (30%) VED and 8 (24%) UST second line. Remission with second-line treatment was achieved in 6 (55%); IFX, 10 (100%); VED and 8 (100%); UST. Remission with third line treatment; was achieved in 1 (100%); VED, 4 (100%); UST.

Conclusion
Our data suggest that treatment with ADA after IFX failure is an effective treatment option whereas IFX treatment after ADA failure is less effective. It is interesting that the majority of those who failed the anti-integrin treatment second line responded to third line ADA. These data are consistent with earlier anti-TNF studies including GAIN (Gauging Adalimumab efficacy in Infliximab Non-responders) and SWITCH (Switch to adalimumab in patients with Crohn’s disease controlled by maintenance infliximab: prospective randomised SWITCH trial) which demonstrated that anti-TNF failure is not a class effect. We recommend prescribing a second anti-TNF after anti-TNF failure in preference to using an anti-integrin second line. This practice will lead to significant cost savings for the health care economy.
P470 The concept of illness identity in inflammatory bowel disease
Authors: Knödler L L , Thomann A , Ebert M P , Lis S , Reindl W 
Published: January 2020

Abstract

Background
Chronic diseases like inflammatory bowel diseases (IBD) can pose challenges to the self-concept of a patient. Illness identity (IID) describes a patient′s way to integrate a chronic illness into the self-concept distinguishing the dimensions rejection, engulfment, acceptance and enrichment. Associations between IID and psychological and physiological functioning have been shown in other chronic diseases, but haven’t been investigated in IBD. In this study, we focus on associations between IID and (i) psychosomatic well-being and (ii) response to biological therapy in patients with IBD.

Methods
Eighty-four patients with active IBD answered questionnaires assessing IID, anxiety, depression, childhood trauma, quality of life (QOL), fatigue and visceral sensitivity (VS.) before the beginning of treatment with biologicals. Response to therapy (n = 73) and changes in the reported outcomes (n = 46) were assessed 3–6 months later. Associations between IID types and QOL, anxiety, depression, childhood trauma, fatigue and VS were examined using Pearson′s correlation. Response to therapy was defined as i) reduction of Harvey Bradshaw-Index (HBI) of &gt;/ = 3 points/Partial Mayo-Score (PMS) of 0–1 points (if HBI &gt;5/PMS &gt;1 at baseline) OR ii) decline of faecal calprotectin or CRP of at least 50% OR iii) confirmation of a significant decline of inflammation in endoscopy/ sonography/MRI. Logistic regression was conducted to examine associations between IID and response to therapy.

Results
IID-rejection was positively associated with anxiety (r = 0.23, p &lt; 0.05), depression (r = 0.28, p &lt; 0.01) and VS. (r = 0.43, p &lt; 0.01). IID-engulfment was associated with lower QOL (r = -0.61, p &lt; 0.01) and more fatigue (r = 0.45, p &lt; 0.01), anxiety (r = 0.66, p &lt; 0.01), depression (r = 0.63, p &lt; 0.01) and VS. (r = 0.74 p &lt; 0.01). In contrast, IID-acceptance was associated with higher QOL (r = 0.34, p &lt; 0.01) and lower levels of fatigue (r = -0.34, p &lt; 0.01), anxiety (r = -0.45, p &lt; 0.01), depression (r = -0.33, p &lt; 0.01), childhood trauma (r = -0.31, p &lt; 0.01) and VS. (r = -0.52, p &lt; 0.01). IID-enrichment was negatively associated with depression (r = -0.3, p &lt; 0.01). Logistic regression indicated no association between IID and response to therapy.

Conclusion
This study is the first to examine the concept of IID in IBD patients. It supports previous findings regarding its association to QOL and psychological well-being in patients with chronic disorders. Contrary to our expectation, IID was not shown to influence treatment response in this cohort, which might be owed to the modest sample size. However, given the strong association between IID and QOL, future studies should investigate the potential of IID as a targetable characteristic in personalised holistic therapy.
P474 Efficacy and safety of GCAP therapy for UC with PSC
Authors: Ito A , Murasugi S , Omori T , Yonezawa M , Tokushige K 
Published: January 2020

Abstract

Background
Primary sclerosing cholangitis (PSC) is a disease with poor prognosis that progresses to cirrhosis due to chronic inflammation of unknown cause. PSC is a progressive disease, and it is essential to control infection such as recurrent cholangitis, so treatment for UC with PSC is desirable because it does not suppress the immune mechanism. Among certain UC treatments, granulocyte adsorption therapy (GCAP) has been reported as a highly safe treatment method with almost no drug load. To clarify the efficacy and safety of GCAP for ulcerative colon associated with PSC. We examined for the purpose.

Methods
We examined patients with PCAP with UC (n = 35) who were in our hospital from April 2000 to July 2019 (n = 9) who were treated with GCAP. Items to be considered Background factors, the presence/absence of steroid combination (0.5 mg/kg or more), 2. Remission induction rate (remission rate after 5 GCAP treatments: remission is defined as CAI is 4 or less), 3. Safety (adverse events caused by GCAP, GCAP We compared the liver function before and after the treatment.

Results
1. Gender (M/F: 4/5), age (age) 45.2 ± 24.3, Affected range (all colitis/right-sided/rectitis 9/0/0), clinical score before GCAP treatment (Lichtiger score: CAI) 7.4 ± 2.0, Alb (g/dl) 3.0 ± 0.9, T-bil (mg/dl) 0.7 ± 0.3, ALP (U/l) 653 ± 390, γ-GTP (U/l) 63.4 ± 27.7, endoscopic score (Mayo 1.5 ± 0.7, UCEIS 2.8 ± 1.5), steroid combination rate was 22.2% 2. Remission induction rate was 77.7% 3. Safety harmful to GCAP the events were only fever (n = 1) and poor return (n = 1). Hepatic function did not deteriorate before and after GCAP.

Conclusion
GCAP was performed in mild to moderate cases, with a high remission rate of 77.7% and fewer steroid combinations. For UC with PSC, GCAP is an effective and safe treatment for induction of remission, suggesting that it may be an option in the future.
P480 Efficiency and safety of endoscopic balloon dilatation of ileocolonic anastomotic strictures in patients with Crohn’s disease: A multicentric retrospective study
Authors: Lukáš M , Kolar M , Vasatko M , Klvana P , Leksa V , Dyntr J , Baca L , Pipek B , Bahnikova B , Summerova S 
Published: January 2020

Abstract

Background
Ileocolonic resection is the most common surgery in Crohn’s disease (CD). However, stricture formation in the anastomosis is considered to be a frequent cause of significant morbidity in CD and a reason for reoperation. Endoscopic balloon dilatation (EBD) is an established modality for non-surgical treatment of strictures in CD, however, summary data from the Czech Republic are lacking.

Methods
All EBDs of CD anastomotic strictures performed in the 7 centres from the Czech Republic between January 1, 2013, and May 30, 2019, were included. Demographics, disease characteristics, concomitant medication and procedure outcomes were analysed. Technical success was defined as an ability to pass the endoscope through the site of the stricture following the procedure. Complications included perforation and bleeding with the need for intervention or hospitalisation. Kaplan–Meier and logistic regression analysis were performed.

Results
In total, 615 procedures performed in 282 patients, 52.1% males, were included. Mean age at the time of the first procedure was 41.9 ± 12.7 years and mean disease duration was 14.5 ± 8.4 years. Single dilatation was performed in 47.9% of patients, 52.1% requested repeated interventions (2–10, median 2). Cumulative probability of redilatation at 6 months, 1 year and 3 years was 20.2% (95% CI 14.8–26.2%), 31.8% (95% CI 26.5–37.2%) and 59.4% (95% CI 55.5–63.0%) respectively. Cumulative probability of a need for reoperation at 6 months, 1 year and 3 years was 4.4% (95% CI 0.5–16.9%), 8.2% (95% CI 2.3–19.3%) and 14.8% (95% CI 7.1–25.2%) respectively. Technical success was reached in 81.1% of procedures and relief of symptoms in 86.7%. The success of the procedure was dependent on the age of the patient (OR 0.98; 95% CI 0.96–0.99), smoking (OR 0.57; 95% CI 0.32–0.98) and concomitant immunosuppression use (OR 1.99; 95% CI 1.31–3.02). Complications occurred in 2.6% of the procedures. Reintervention until 6 months after the procedure was needed in 26.7% of cases, out of which repeated dilatation in 21.3% of cases and early surgery took place in 5.4% of cases. The technical success (OR 0.44; 95% CI 0.29–0.67) and repeated dilatation (OR 1.57; 95% CI 1.09–2.27) were significantly associated with the need for reintervention until 6 months.

Conclusion
In a large multicentric Czech cohort, the EBD in Crohn’s disease anastomotic strictures was proven to be safe and effective with results comparable to the available international data.
P489 Are patients with inflammatory bowel disease receiving an adequate immunisation?
Authors: Simian D , Núñez P , Flores L , Figueroa C , Ibáñez P , Kronberg U , Lubascher J , Pizarro G , Quera R 
Published: January 2020

Abstract

Background
Inflammatory Bowel Disease (IBD) treatment may increase the risk of infections. Vaccines are part of the comprehensive IBD patient care. The aim of this study was to describe indications and adherence of immunisations in IBD and identify possible associated factors.

Methods
A cross-sectional, analytic study was conducted in patients from an IBD Program of a tertiary centre in Chile, between April – June 2019. Demographic and clinical data were obtained from the hospital IBD registry, approved by the local IRB. Patients were asked to answer a vaccine survey and complementary information was obtained from the National Immunization Registry. Descriptive and association statistic were used (χ2; p &lt;0.05).

Results
A total of 243 patients were included (Table 1). The influenza vaccine rate has significantly increased (Figure 1), reaching 67% in 2019, being higher in women (66% vs. 34%; p 0.045) and patients in biological therapy (BT) (29% vs. 14%; p 0.011) (Table 1). Vaccination rates are shown in Figure 2. Combination of Influenza/Hepatitis B/Pneumococcus vaccines was administered in 56 patients (23%), significantly higher in patients with BT and with fewer years of IBD. Forty patients received a live virus vaccine, 18% were on immunomodulatory treatment. The survey showed that 57 patients (23%) have not been immunised with any vaccine, mainly due to lack of time, lack of medical prescription and high cost.

Conclusion
In this cohort, vaccination rates are low, however, adherence to Influenza vaccine has increased. Immunisation should be considered early by the multidisciplinary team, educating patients about its importance.